Clinical Research

Furthering science, research & medical developments.

Florida Medical Clinic is proud to make a difference by conducting innovative clinical trials to further clinical advancement. Numerous clinical research studies are conducted on an ongoing basis to help further science, research and medical development.

New and exceptional medications waiting for FDA approval are tested in our Clinical Research Department. Nationwide patient results are monitored and evaluated by the FDA in an effort to constantly improve medical treatments. The study length varies according to the test criteria.

Your physician can advise you about your eligibility for clinical research. Medical care, medications, and possible compensation are available to qualified patients who volunteer for a clinical trial.

Contact Us

If you would like additional information on any study listed, please contact:

William D. Johnston RN CCRC
813.780.8368
wjohnston@floridamedicalclinic.com

Our Current Clinical Trials

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Study Title

A Randomized, Parallel-group, Double-blind, Placebo-controlled, Multicenter Phase III Trial to Investigate the Efficacy and Safety of Secukinumab 300 mg and 150 mg Administered Subcutaneously Versus Placebo, in Combination With a Glucocorticoid Taper Regimen, in Patients With Giant Cell Arteritis (GCA) (GCAptAIN)

Protocol Name: GCAptAIN
Protocol Number: CAIN457R12301

Description: Randomized, parallel-group, double-blind, placebo-controlled, multi-center, Phase III study to evaluate the efficacy of Secukinumab in combination with a 26-week prednisone taper regimen compared to placebo in combination with a 52-week prednisone taper regimen

Eligibility:

Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study.
2. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study.
3. Male or non-pregnant, non-lactating female patients at least 50 years of age.
4. Diagnosis of GCA based on meeting all of the following criteria:
   • Age at onset of disease ≥ 50 years.
   • Unequivocal cranial symptoms of GCA (e.g., new-onset localized headache, scalp or temporal artery tenderness, permanent or temporary ischemia-related vision loss, or otherwise unexplained mouth or jaw pain upon mastication), and/or unequivocal symptoms of polymyalgia rheumatica (PMR) (defined as shoulder and/or hip girdle pain associated with inflammatory morning stiffness) and/or symptoms of limb ischemia (claudication).
   • TAB revealing features of GCA and/or cross-sectional imaging study such as ultrasound (e.g., cranial or axillary), MRI/MRA, CTA, or PET-CT with evidence of vasculitis.
5. Active disease as defined by meeting both of the following within 6 weeks of BSL (see Section 8.1 for details)
   • Presence of signs or symptoms attributed to active GCA and not related to prior damage (e.g., visual loss that occurred prior to 6 weeks before BSL without new findings occurring within 6 weeks of BSL)
   • Elevated ESR ≥ 30 mm/hr or CRP ≥ 10 mg/L attributed to active GCA or active GCA on TAB or on imaging study.
6. Patients to meet definition of new-onset GCA or relapsing GCA:
   • Definition of new-onset GCA*: GCA that is diagnosed within 6 weeks of BSL visit
   • Definition relapsing GCA:
   • GCA diagnosed > 6 weeks before BSL visit and
   • Following institution of an appropriate treatment course for GCA, participant has experienced recurrence of active symptoms or signs of disease after resolution.
     • The 6-week timeframe is to be calculated from the date of suspected GCA diagnosis. Suspected diagnosis is defined as date when GC therapy was initiated.
7. Patients’ current GCA episode should be treatable with a dose of prednisone (or equivalent) designed to adequately achieve disease control in accordance with international guidelines. If this is not possible due to concerns regarding GC toxicity, the patient should not be enrolled. It must be medically appropriate for the patient to receive prednisone (or equivalent) 20 mg-60 mg daily (or equivalent) at BSL.
8. Patients taking MTX (≤ 25 mg/week) are allowed to continue their medication provided they have taken it for at least 2 months and are on a stable dose for at least 4 weeks prior to randomization and if they are on stable folic acid treatment before randomization.

Exclusion Criteria:

1. 1. Pregnant or nursing (lactating) women where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
2. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during study treatment or longer if required by locally approved prescribing information (e.g., in European Union (EU) 20 weeks after treatment discontinuation). Also, contraception should be used in accordance with locally approved prescribing information of concomitant medications administered (e.g., rescue treatment). Effective contraception methods include:
   • Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
   • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least 6 weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.
   • Male sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient
   • Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps). NOTE: for United Kingdom: with spermicidal foam/gel/film/cream/vaginal suppository.
   • Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
   • Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age-appropriate history of vasomotor symptoms). Women are considered not of child-bearing potential if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks prior to enrollment on study. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered to be not of child-bearing potential.
   • If local regulations are more stringent than the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the Informed Consent Form (ICF).
3. Previous exposure to Secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor.
4. Patients treated with any cell-depleting therapies.
5. Previous participation in a clinical trial where the outcome of treatment with the GCA drug is unknown. This does not include trials where the treatment for GCA was GCs, MTX, leflunomide or azathioprine
6. Patients who have been treated with inhibitors directly targeting IL-1, or IL-1 receptor, IL-12 and IL-23, or abatacept within 4 weeks or within 5 half-lives of the drug (whichever is longer) prior to BSL.
7. Treatment with tocilizumab, other IL-6/IL6-R inhibitor or JAK inhibitor within 12 weeks or within 5 half-lives of the drug (whichever is longer) prior to BSL, or if the patient did not respond to or experienced a relapse during treatment any time before BSL.
8. Any treatment received for GCA in which patient did not respond to treatment or experienced a relapse while on that treatment any time before BSL. This also includes patients who were treated in a clinical trial for GCA. Patients who failed on treatment with GCs, MTX, leflunomide and/or azathioprine may be included.
9. Patients treated with i.v. immunoglobulins or plasmapheresis within 8 weeks prior to BSL.
10. Patients treated with cyclophosphamide or hydroxychloroquine within 6 months prior to BSL, or tacrolimus, everolimus, cyclosporine A, azathioprine, sulfasalazine, mycophenolate mofetil within 4 weeks prior to BSL.
11. Patients treated with leflunomide within 8 weeks of BSL unless a cholestyramine washout has been performed in which case the patient must be treated within 4 weeks of BSL.
12. Patients treated with an alkylating agent within 5 years prior to BSL, unless specified in other exclusion criteria.
13. Patients requiring or anticipated to require systemic chronic glucocorticoid therapy or pulses of glucocorticoids for reasons other than GCA (e.g., COPD, asthma, planned surgery) at screening or randomization.
14. Criterion removed in protocol V01.
15. Patients requiring chronic (i.e., not occasional “prn”) high potency opioid analgesics for pain management.
16. Use of other investigational drugs within 5 half-lives of enrollment or within 30 days (e.g. small molecules) or until the expected pharmacodynamic effect has returned to BSL (e.g., biologics), whichever is longer; or longer if required by local regulations.
17. History of hypersensitivity or contraindication to any of the study treatments or its excipients or to drugs of similar chemical classes.
18. Active IBD or other ongoing inflammatory diseases other than GCA that might confound the evaluation of the benefit of Secukinumab therapy, including uveitis at screening or randomization.
19. Major ischemic event (e.g., myocardial infarction, stroke, etc.) or transient ischemic attack (TIA) (except ischemia-related vision loss), related or unrelated to GCA, within 12 weeks of screening.
20. Confirmed diagnosis of any primary form of systemic vasculitis, other than GCA.
21. Any other biologics (e.g., denosumab, TNFα inhibitors) within 4 weeks or within 5 half-lives of the drug (whichever is longer) prior to BSL, or anticipated use of a biologic prior to EOS.
22. Active ongoing diseases which in the opinion of the investigator immunocompromises the patient and/or places the patient at unacceptable risk for treatment with immunomodulatory therapy.
23. Significant medical problems or diseases, including but not limited to the following: uncontrolled hypertension (≥ 160/95 mmHg), congestive heart failure (New York Heart Association (NYHA) status of class III or IV) and uncontrolled diabetes mellitus.
24. History of clinically significant liver disease or liver injury as indicated by abnormal liver function tests (LFTs) such as Aspartate Aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) or serum bilirubin. The investigator should be guided by the following criteria:
    • SGOT (AST) and SGPT (ALT) may not exceed 3 × the upper limit of normal (ULN). A single parameter elevated up to and including 3 × ULN should be re-checked once more as soon as possible, and in all cases, at least prior to randomization, to rule-out laboratory error.
    • Alkaline phosphatase may not exceed 2 × ULN. An elevation up to and including 2 × ULN should be re-checked once more as soon as possible, and in all cases, at least prior to randomization, to rule-out laboratory error.
    • Total bilirubin may not exceed 2 × ULN. If the total bilirubin concentration is increased above 2 × ULN, total bilirubin should be differentiated into the direct and indirect reacting bilirubin.
25. Criterion removed in protocol V01
26. Screening total WBC count < 3,000/μL, or platelets < 100,000/μL or neutrophils < 1,500/μL or Hgb < 8.3 g/dL (83 g/L).
27. Active infections during the last 2 weeks prior to randomization.
28. History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection as defined by a positive QuantiFERON TB-Gold Plus test. Patients with a positive test may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active TB. If the test result is indeterminate, the investigator may repeat the test once or may proceed directly to perform the work-up for TB as per local procedures. If presence of latent TB is established then treatment according to local country guidelines must be initiated prior to randomization.
29. Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C at screening or randomization (if not treated and cured).
30. History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for basal cell carcinoma or actinic keratosis that have been treated with no evidence of recurrence in the past 3 months, carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed).
31. Live vaccinations (e.g., monkey pox vaccine, oral polio vaccine, varicella/zoster vaccines) within 6 weeks prior to BSL, or planned or anticipated potential need for live vaccination during study participation until 12 weeks after last study treatment administration.
32. Current severe progressive or uncontrolled disease, which in the judgment of the clinical investigator renders the patient unsuitable for the trial.
33. Any medical or psychiatric condition, which, in the investigator’s opinion, would preclude the patient from adhering to the protocol or completing the study per protocol.
34. Donation or loss of 400 mL or more of blood within 8 weeks before randomization.
35. History or evidence of ongoing alcohol or drug abuse, within the last 6 months before randomization.
36. Specific for MRI/MRA imaging sub-study: absolute contraindications to MRI/MRA (e.g., metallic implants, metallic foreign bodies, pacemaker, defibrillator) and to the use of gadolinium-based agents (e.g., people with severe kidney failure, patients with previous severe allergic/anaphylactoid reaction to a gadolinium-based contrast agent); patients with severe renal disease [eGFR <30 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)], or acutely deteriorating renal function, who would be at risk of nephrogenic systemic fibrosis. Subjects with renal impairment of a lesser severity may be excluded from the imaging sub study in accordance with local practice.

Start Date: October 6, 2021

Projected End Date: April 14, 2027

ClinicalTrials.gov Identifier: NCT04930094

Study Web Address for Potential Patients: https://gcapmrclinicaltrial.com

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Study Title

A Randomized, Parallel-group, Double-blind, Placebo-controlled, Multicenter Phase III Trial to Evaluate Efficacy and Safety of Secukinumab Administered Subcutaneously Versus Placebo, in Combination With a Glucocorticoid Taper Regimen, in Patients With Polymyalgia Rheumatica (PMR)

Protocol Name:  CAIN457C22301
Protocol Number: CAIN457C22301

Description:  This is a multicenter, randomized, double-blind, placebo-controlled, parallel group study with two Secukinumab dose regimens in approximately 360 PMR patients who had recently relapsed. The study consists of: screening (up to 6 weeks); treatment period (52 weeks, with last IMP administration at 48 weeks, active drug or placebo) in combination with prednisone tapered over 24 weeks; treatment-free follow-up (up to 24 weeks). Adult males and females of at least 50 years of age with a recent PMR relapse (within 12 weeks from Baseline) will be included. Dosing will be once every week for the first 4 weeks, and once every 4 weeks thereafter via pre-filled syringe.

The primary objective is to demonstrate the efficacy of Secukinumab 300 mg subcutaneously in combination with a 24-week glucocorticoid (GC) taper regimen compared with placebo with respect to the proportion of patients in sustained remission at Week 52. Primary secondary objectives are to assess difference in proportion of patients achieving complete sustained remission at Week 52, adjusted annual cumulative GC dose and time to first use of escape treatment or rescue treatment through Week 52. Key safety data will be collected, along with Patient Reported Outcomes.

Eligibility:

Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study
• Male or non-pregnant, non-lactating female participants at least 50 years of age.
• Diagnosis of PMR according to the provisional American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria: Participants ≥ 50 years of age with a history of bilateral shoulder pain accompanied by elevated C-reactive protein (CRP) concentration (≥ 10 mg/L) and/or elevated erythrocyte sedimentation rate (ESR) (≥ 30 mm/hr) who scored at least 4 points from the following optional classification criteria:
  • Morning stiffness > 45 minutes (min) (2 points)
  • Hip pain or restricted range of motion (1 point)
  • Absence of rheumatoid factor and/or anti-citrullinated protein antibodies (2 points)
  • Absence of other joint involvement (1 point)
• Participants must have a history of being treated for at least 8 consecutive weeks with prednisone (≥ 10 mg/day or equivalent) at any time prior to screening
• Participants must have had at least one episode of PMR relapse while attempting to taper prednisone at a dose that is ≥ 5 mg/day (or equivalent) within the past 12 weeks prior to BSL. Diagnosis of a PMR relapse is defined as participant meeting both of the following:
  • Recurrence of bilateral shoulder girdle and/or bilateral hip girdle pain associated with inflammatory stiffness with or without additional symptoms indicative of PMR relapse (such as constitutional symptoms) within 12 weeks prior to BSL that are in the opinion of the Investigator not due to other diseases that may mimic PMR such as osteoarthritis in shoulders or hips, polyarticular calcium pyrophosphate deposition disease, rotator cuff disease, adhesive capsulitis (frozen shoulder) or fibromyalgia.
  • Elevated ESR (≥ 30 mm/hr) and/or elevated CRP (> upper limit of normal (ULN)) attributable to PMR at the time of relapse and/or at screening
• Participants must have been treated as per local treatment recommendations following the latest PMR relapse and must be on prednisone of at least 7.5 mg/day (or equivalent) and not exceeding 25 mg/day at screening and during the screening period

Exclusion Criteria:

• Evidence of GCA as indicated by typical (cranial) symptoms (e.g., persistent or recurrent localized headache, temporal artery or scalp tenderness, jaw claudication, blurry or loss of vision, symptoms of stroke), extremity claudication, imaging and/or temporal artery biopsy result
• Concurrent rheumatoid arthritis or other inflammatory arthritis or other connective tissue diseases, such as but not limited to systemic lupus erythematosus, systemic sclerosis, vasculitis, myositis, mixed connective tissue disease, and ankylosing spondylitis
• Concurrent diagnosis or history of neuropathic muscular diseases
• Inadequately treated hypothyroidism (e.g., persistence of symptoms, lack of normalization of serum TSH despite regular hormonal replacement treatment)
• Previous exposure to Secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor
• Participants treated with tocilizumab or other IL-6/IL6-receptor inhibitors within 12 weeks or within 5 half-lives (whichever is longer) prior to BSL; participant who did not respond to or experienced a relapse during treatment are excluded from enrollment into the study Other protocol-defined inclusion/exclusion criteria may apply

Start Date: March 22, 2023

Projected End Date: December 22, 2025

ClinicalTrials.gov Identifier: NCT05767034

Study Web Address for Potential Patients: https://gcapmrclinicaltrial.com

 

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Study Title

A Randomized, Double-blind, Placebo-controlled, Multicentre, Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With Non-Cirrhotic Non-alcoholic Steatohepatitis (NASH) and Fibrosis Stages F2 and F3

Protocol Name: NATiV3
Protocol Number: 337HNAS20011

Description: Primary objectives

This Phase 3 study is conducted to evaluate Lanifibranor in adults with NASH and liver fibrosis stage F2 or F3 and consists of 2 sequential parts – an initial double-blind placebo-controlled (DBPC) period (Part A) followed by a double-blind active treatment extension (ATE) period (Part B), with the following primary objectives:

Part A To assess the safety and efficacy of Lanifibranor compared to placebo on ‘NASH resolution and improvement of fibrosis’ assessed by liver histology.

Part B To assess the safety of Lanifibranor beyond the DBPC period. Secondary objectives

Key secondary objectives of Part 1:

• To assess the effect of Lanifibranor compared to placebo on NASH resolution and no worsening of fibrosis
• To assess the effect of Lanifibranor compared to placebo on improvement of fibrosis with no worsening of NASH

Other secondary objectives of both Part 1 and Part 2:

• To assess the effect of Lanifibranor on other key histological features of NASH (only for DBPC period)
• To assess the effect of Lanifibranor on NASH resolution and improvement of fibrosis in diabetic patients (only for DBPC period)
• To assess the effect of Lanifibranor on liver tests
• To assess the effect of Lanifibranor on glycaemic parameters
• To assess the effect of Lanifibranor on lipid parameters
• To assess the effect of Lanifibranor on liver stiffness and steatosis assessed by elastography.
• To assess the effect of Lanifibranor on health-related quality of life
• To assess the safety of Lanifibranor
• To assess population PK modeling through plasma levels of Lanifibranor using sparse sampling scheme (only for DBPC period)

Eligibility:

Inclusion Criteria:

Prescreening Criteria:

• Diagnosed with NASH on prior liver biopsy
• Type 2 diabetes with high waist circumference or obesity or hepatic steatosis on ultrasound
• At least 3 of the components of metabolic syndrome

Inclusion Criteria:

1. Male or female, aged ≥18 years at the time of signing informed consent
2. Upon central biopsy reading process: diagnosis of NASH according to the Steatosis-Activity-Fibrosis (SAF):
   1. Steatosis score ≥1
   2. Activity score: A3 or A4
   3. Fibrosis score: F2 or F3
3. No qualitative change in dose for the drugs listed below:
   1. Antidiabetic treatment if glucagon-like peptide-1 receptor agonists (GLP1 receptor agonists) or sodium-glucose co-transporter-2 inhibitors (SGLT2 inhibitors): for at least 3 months
   2. Vitamin E (if at a dose ≥400 IU/day): for at least 6 months
   3. Statins: for at least 3 months
4. No qualitative change in dose for all other chronically administered drugs for at least 3 months prior to Screening
5. Weight stable for 6 months prior to Screening and between the qualifying liver biopsy and Baseline (no more than 5% change for both periods)
6. Negative serum pregnancy test at study Screening for females of childbearing potential confirmed by central laboratory. Females of childbearing potential must practice a consistent and proper use of highly effective method of contraception throughout the study and for 1 month after treatment discontinuation.

Exclusion Criteria:

Liver-related:

1. Documented causes of chronic liver disease other than NASH
2. Histologically documented liver cirrhosis (fibrosis stage F4)
3. History or current diagnosis of hepatocellular carcinoma (HCC)
4. History of or planned liver transplant
5. Positive human immunodeficiency virus (HIV) serology
6. ALT or AST >5 × ULN
7. AST<0.6 ULN if the liver biopsy has to be performed in the scope of the study
8. Abnormal synthetic liver function as defined by Screening central laboratory evaluation
9. Haemoglobin <110 g/L (11 g/dL) for females and <120 g/L (12 g/dL) for males
10. Patient currently receiving any approved treatment for NASH or obesity
11. Current or recent history (<5 years) of significant alcohol consumption
12. Treatment with drugs that may cause non-alcoholic fatty liver disease (NAFLD) administered for at least 2 weeks within 12 months prior to qualifying liver biopsy

Glycaemia related:

1. HbA1c >9% at Screening
2. Diabetes mellitus other than type 2
3. Current treatment with insulin
4. Treatment with PPAR-gamma agonists (thiazolidinediones [TZDs]) 12 months before screening or historical biopsy.

Obesity related:

1. Bariatric surgery: Restrictive procedures are allowed, if performed >6 months prior to the qualifying liver biopsy; malabsorptive procedures and procedures combining both restrictive and malabsorptive methods are not allowed within 5 years of the qualifying liver biopsy.

Cardiovascular related:

1. History of heart failure with reduced left ventricular ejection fraction (LVEF)
2. Atrial fibrillation requiring anticoagulation
3. Unstable heart failure
4. Uncontrolled hypertension at Screening (values >160/100 mm Hg)

General safety:

1. Women currently breastfeeding
2. Previous exposure to Lanifibranor
3. Participation in any clinical trial investigational medicinal product/device within 3 months from Screening or 5 half-lives from Screening, whichever is longer
4. Concomitant treatment with PPAR-alpha agonists (fibrates)

Start Date: August 19, 2021

Projected End Date: September 30, 2026

ClinicalTrials.gov Identifier: NCT04849728

Study Web Address for Potential Patients: http://nash-trial.com/

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Study Title

REBYOTA™ for the Prevention of Recurrence of Clostridioides Difficile Infection (CDI) in Adult Patients: An Observational Study

Protocol Name:  ROAR
Protocol Number: 000422

Description: This is a prospective observational cohort study designed to collect data on patients who received REBYOTA™ for the prevention of rCDI in the routine care setting. As all data collected for this study are observational, the decision to prescribe REBYOTA™ is at the treating physician’s discretion and independent from the decision to enroll the patient in the study. Data will be collected from patients’ medical records after obtaining informed consent. Data about clinical history, CDI events (primary and recurrent: severity, treatment), CDI-related symptoms, treatments, medical procedures, Adverse Events (AEs), and healthcare resource utilization (i.e., hospitalizations and re-admissions) will be collected through 6 months of follow-up from the date of REBYOTA™ administration.

 Eligibility:

Inclusion Criteria:

• Signed and dated informed consent form (ICF)
• Age ≥ 18 years
• Diagnosis of rCDI as determined by the treating physician
• Completed antibiotic treatment for the presenting rCDI episode
• Prescription for REBYOTA™ to prevent rCDI according to the approved indication

Exclusion Criteria:

• Currently enrolled in an interventional clinical trial

Start Date: June 19, 2023

 Projected End Date: May 5, 2025

ClinicalTrials.gov Identifier: NCT05835219

Study Web Address for Potential Patients: N/A

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Study Title

A Phase 3B, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis Who Had an Inadequate Response and/or Intolerance to One Prior Anti-Tumor Necrosis Factor Alpha Agent

Protocol Name:  SOLSTICE
Protocol Number: CNTO1959PSA3005

Description: PsA is a chronic, immune-mediated inflammatory disease characterized by peripheral joint inflammation, enthesitis, dactylitis, axial disease, and the skin lesions associated with psoriasis. Guselkumab is a fully human monoclonal antibody (mAb) that binds to p19 protein subunit of interleukin (IL)-23 and blocks the binding of extracellular IL-23 to the cell surface IL-23 receptor, inhibiting IL-23 specific intracellular signaling, subsequent activation, and cytokine production. The primary hypothesis of this study is that Guselkumab is superior to placebo as assessed by the proportion of participants who had an inadequate response (IR) and/or intolerance to one prior anti-tumor necrosis factor (anti-TNF) achieving an American College of Rheumatology 20 (ACR 20) response at Week 24. This study will consist of a screening phase (up to 6 weeks), blinded treatment phase (approximately up to 2 years), which includes a placebo-controlled period from Week 0 to Week 24, and an active-controlled treatment phase from Week 24 to Week 100, and safety follow-up phase (Week 112). Safety assessments will include physical examinations, vital signs, height, weight, electrocardiograms, and clinical safety laboratory assessments. The total duration of the study will be up to 118 weeks.

 Eligibility:

Inclusion Criteria:

• Have a diagnosis of active psoriatic arthritis (PsA) for at least 6 months before the first administration of study agent and meet Classification criteria for Psoriatic Arthritis (CASPAR) at screening
• Have active PsA as defined by: at least 3 swollen joints and at least 3 tender joints at screening and at baseline; and C-reactive protein (CRP) greater than or equal to (>=) 0.3 milligrams per deciliter (mg/dL) at screening from the central laboratory
• Have at least one of the following PsA subsets: distal interphalangeal joint involvement, polyarticular arthritis with absence of rheumatoid nodules, asymmetric peripheral arthritis, or spondylitis with peripheral arthritis
• Have active plaque psoriasis, with at least one psoriatic plaque of >= 2 centimeters (cm) diameter and/or nail changes consistent with psoriasis, or documented history of plaque psoriasis
• Have an inadequate response and/or intolerance to anti-tumor necrosis factor alpha (TNF alpha) therapy, defined as presence of active PsA despite previous treatment with one prior anti-TNF alpha agent

Exclusion Criteria:

• Has other inflammatory diseases that might confound the evaluations of benefit of Guselkumab therapy in the treatment of PsA, including but not limited to rheumatoid arthritis, ankylosing spondylitis/nonradiographic axial spondyloarthritis, systemic lupus erythematosus, or Lyme disease
• Has received more than 1 prior anti-tumor necrosis factor (TNF) alpha agent (or biosimilars)
• Has ever received Janus kinase (JAK) inhibitor including but not limited to tofacitinib, baricitinib, filgotinib, peficitinib, decernotinib, upadacitinib or any other investigational JAK inhibitor
• Has received any systemic immunosuppressants (example, azathioprine, cyclosporine, 6 thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, tacrolimus) within 4 weeks of the first administration of study intervention
• Has known allergies, hypersensitivity, or intolerance to Guselkumab or its excipients
• Has a history of chronic or recurrent infectious disease, including but not limited to chronic renal infection, chronic chest infection (example, bronchiectasis), recurrent urinary tract infection (example, recurrent pyelonephritis or chronic non-remitting cystitis), fungal infection (example, mucocutaneous candidiasis), or open, draining, or infected skin wounds or ulcers

Start Date: September 28, 2021

 Projected End Date: September 7, 2026

ClinicalTrials.gov Identifier: NCT04936308

Study Web Address for Potential Patients: N/A

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Study Title

A Randomized Double-blind Placebo-controlled Phase 3 Study to Evaluate the Effect of Resmetirom on Liver-related Outcomes in Patients With Well-compensated (Child-Pugh A) Non-alcoholic Steatohepatitis (NASH) Cirrhosis (MAESTRO-NASH-OUTCOMES)

Protocol Name:  MAESTRO
Protocol Number: MGL-3196-19

Description: This is a multi-national, multicenter, double-blind, randomized, placebo-controlled study in participants with well-compensated NASH cirrhosis. Participants will be randomized 3:1 in a blinded manner to receive 80 mg Resmetirom or matching placebo given orally once daily in the morning for the duration of the study and until the required number of Composite Clinical Outcome events are achieved. Composite Clinical Outcome events are defined as any of the following: all-cause mortality, liver transplant, and significant hepatic events, including potential hepatic decompensation events (ascites, hepatic encephalopathy, or gastroesophageal variceal hemorrhage), and confirmed increase of Model for End-stage Liver Disease (MELD) score from <12 to ≥15. The study comprises an up to 60-day screening period and an approximately 3-year treatment period.

 Eligibility:

Inclusion Criteria:

• Definitive (by histologic documentation) or probable NASH as causative agent for cirrhosis, following a modified version of the NASH Cirrhosis: Liver Forum Consensus Definitions for Clinical Trials.
• a. Most recent biopsy (within last 5 years) shows cirrhosis with a NAS of ≥ 2, and at least two components: one being steatosis and at least one other component; OR NAS of ≥ 2, if steatosis = 0 or is ungraded with inflammation and/or ballooning, eligible with an MRI-PDFF >5%. If steatosis and ballooning and/or steatosis and inflammation are noted by the local pathologist, then the biopsy qualifies even if a NAS is not provided (Approximately 70% of the study patient population) b. Historical biopsy (within last 5 years) showed NASH with significant fibrosis with pathology report documenting “F2” or “F3”, with at least steatosis either by biopsy with no minimal percentage required or by MRI-PDFF >5%, AND inflammation or ballooning. Now with cirrhosis, either by clinical history or current features, imaging, noninvasive tests, or biopsy (see Appendix 7) (Up to approximately 20% of study patient population) c. Historical biopsy (within last 5 years) shows steatosis. Pathology report documents steatosis with no minimal percentage required. Now with cirrhosis, either by clinical history or current features, imaging, noninvasive tests, or biopsy (see Appendix 7). Prescreening metabolic risk factors must include obesity and/or T2D. (Up to approximately 10% of study patient population.)
• Well-compensated NASH cirrhosis at screening and baseline with Child-Pugh A (score of 5-6) (no history of hepatic decompensation event).
• At least 3 metabolic risk factors
• Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) that is obtained during the Screening period or a historic MRI-PDFF at ≤8 weeks old at the time of randomization with no weight change ≥5% weight change in that interval.
• MRE ≥4.2 where MRE is available.
• Enhanced liver function (ELF) ≥9.8, only if MRE is unavailable or contraindicated.

Exclusion Criteria:

• Participants with a chronic liver diseases other than NASH cirrhosis, such as primary biliary cholangitis, primary sclerosing cholangitis, Hepatitis B positive, Hepatitis C, history or evidence of current active autoimmune hepatitis, history or evidence of Wilson’s disease, history or evidence of alpha-1-antitrypsin deficiency, history or evidence of genetic hemochromatosis (hereditary, primary), evidence of drug-induced liver disease, as defined on the basis of typical exposure and history, known bile duct obstruction, or suspected or confirmed liver cancer, are excluded.
• Participants with MELD score ≥12 due to liver disease are excluded.
• Participants with a history of hepatic decompensation or impairment are excluded.

Start Date: August 26, 2022

 Projected End Date: November 2025

ClinicalTrials.gov Identifier: NCT05500222

Study Web Address for Potential Patients: N/A

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Study Title

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy and Safety of Rifaximin Soluble Solid Dispersion (SSD) for the Delay of Encephalopathy Decompensation in Cirrhosis

Protocol Name:  RNLC3132
Protocol Number: RNLC3132

Description: Study RNLC3132 is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of rifaximin SSD-40mg IR for the delay of the first episode of overt hepatic encephalopathy (OHE) decompensation in liver cirrhosis, defined by the presence of medically controlled ascites.

Eligibility:

Inclusion Criteria:

• Diagnosis of liver cirrhosis with medically controlled ascites (>30 days) not requiring therapeutic paracentesis (could have had paracentesis in the past).
• Conn (West Haven Criteria) score of < 2.
• Mini-Mental State Examination (MMSE) score > 24 at screening.
• ≥ 18 and ≤ 85 years of age.

Exclusion Criteria:

• Active COVID-19 that is unresolved
• History of SBP
• History of EVB or AKI-HRS within 6 months
• History of OHE episode (Conn score ≥ 2)

Start Date: August 3, 2022

 Projected End Date: January 2025

ClinicalTrials.gov Identifier: NCT05297448

Study Web Address for Potential Patients: N/A

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Study Title

A Seamless, Adaptive, Phase 2b/3, Double-Blind, Randomized, Placebo-controlled, Multicenter, International Study Evaluating the Efficacy and Safety of Belapectin (GR MD-02) for the Prevention of Esophageal Varices in NASH Cirrhosis

Protocol Name: NAVIGATE
Protocol Number: GT-031
Description: Study Evaluating the Efficacy and Safety of Belapectin for the Prevention of Esophageal Varices in NASH Cirrhosis (NAVIGATE)
Eligibility: 18 Years to 75 Years

Inclusion Criteria:

1. Is male or female, ≥ 18 and ≤ 75 years of age at the time of Screening.
2. Is willing and able to provide written informed consent prior to the initiation of any study-specific procedures.
3. Has evidence of portal hypertension, with either one of the following:
   • platelet count <150,000/mm3
   • documented HVPG measurement >6 mmHg OR
   • at least two of the following:
     • spleen size ≥14 cm (documented by ultrasound, MRI, or CT scan)
     • abdominal collateral circulation (documented by ultrasound, MRI, or CT scan or physical examination, ie, caput medusae)
     • documented liver transient elastography (eg, FibroScan) ≥20 kPa.

4. Has a history confirming nonalcoholic steatohepatitis (NASH) cirrhosis, with at least one of the following:
   • There is a historical liver biopsy showing cirrhosis with steatohepatitis. There is no evidence for a competing etiology for the cirrhosis.
   • There is a historical liver biopsy showing steatohepatitis, and there is evidence of cirrhosis from clinical or imaging data or a second liver biopsy showing cirrhosis without all features of NASH (as the histological NASH lesions may have burnt out). There is no evidence for a competing etiology. There is at least 1 co-existing metabolic comorbidity at Screening: obesity (with either body mass index [BMI] ≥30 kg/m2 or waist circumference ≥102 cm [40 in, men] or ≥88 cm [35 in, women], or by ethnically appropriate cutpoints); hypertension (either on anti hypertensive drug therapy for at least 1 year or systolic/diastolic blood pressure (BP) >140/80 mm Hg); Type 2 diabetes (glycated hemoglobin [HbA1c] ≥6.5%, or on anti-diabetic medication for at least 1 year); or dyslipidemia (triglycerides ≥150 mg/dL or on drug therapy for hypertriglyceridemia for at least 6 months; high-density lipoprotein cholesterol ≤40 mg/dL [men] or ≤50 mg/dL [women]) to corroborate a diagnosis of nonalcoholic fatty liver disease (NAFLD).
   • There is a historical liver biopsy showing cirrhosis with steatosis but not steatohepatitis. There is no evidence for a competing etiology. There are at least 2 co-existing (or history of) metabolic comorbidities (with obesity or diabetes being one of them) to corroborate a diagnosis of NAFLD.
   • There is a historical liver biopsy showing steatosis but now with cirrhosis either by clinical examination, imaging, or biopsy. If there is a current biopsy, it does not show evidence of steatosis or steatohepatitis as histological lesions may have burned out. There is no evidence for a competing etiology. There are at least 2 co existing (or history of) metabolic comorbidities (with obesity or diabetes being one of them) to corroborate a diagnosis of NAFLD.
   • For patients without a historical liver biopsy with slides available for review by the central study pathologist, a screening liver biopsy is required.
     • Note: All liver biopsy blocks and/or slides for eligibility assessments (including those from historical biopsies) will be reviewed by the central study pathologist while the subject is in Screening, and must meet definitions for diagnosis of either Definitive cirrhosis or Probable cirrhosis. Results from the central study pathologist must be available before the subject is randomized.

5. Absence of hepatocellular carcinoma (HCC) by valid imaging (eg, ultrasound, CT scan, or MRI) within 6 months prior to randomization. If no such imaging result is available, then ultrasound imaging should be performed as part of standard of care.
6. Patients with diabetes mellitus can be enrolled, if they are adequately controlled on a stable dose or doses of antidiabetic medication(s) for at least 3 months before Screening, and their screening HbA1c is ≤9.5%.
7. Patients on vitamin E or pioglitazone can be enrolled if they are on a stable dose and regimen for at least 3 months before screening, and the dose is expected to be held constant during the trial.
8. Patients on a statin can be enrolled if they are on a stable regimen for at least 3 months before Screening, and expected to be held stable during the trial.
9. Is not pregnant and must have a negative serum pregnancy test result prior to randomization.
10. Is of non-childbearing potential or if a fertile man or woman participating in heterosexual relations, agrees to use two acceptable means of contraception (ie, 2 effective methods of contraception, one of which must be a physical barrier method [eg, male or female condom, diaphragm] when combined with a highly effective method of contraception [ie, a method with a failure rate of <1% per year when used consistently and correctly]) throughout his/her participation in this study and for 90 days after discontinuation of study treatment.
    • Highly effective forms of contraception include:
      • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (such as oral, intravaginal, transdermal) methods
      • progestogen-only hormonal contraception associated with inhibition of ovulation (such as oral, injectable, implantable)
      • hormone-releasing intrauterine system (IUS)
      • intrauterine device (IUD)
      • bilateral tubal occlusion
      • a vasectomized partner, provided that partner is the sole sexual partner of the women of childbearing potential trial participant and that the vasectomized partner has received medical assessment of the surgical success
      • sexual abstinence (ie, a refraining from heterosexual intercourse during the entire period of the clinical trial, if it is the preferred and usual lifestyle of the subject).Surgically sterile males and females are not required to use contraception provided they have been considered surgically sterile for at least 6 months. Surgical sterility includes history of surgically successful vasectomy, hysterectomy, or bilateral salpingo-oophorectomy. Postmenopausal women who have been amenorrheic for at least 2 years at the time of Screening will be considered sterile.

11. If a lactating woman, agrees to discontinue nursing before the start of study treatment and refrain from nursing until 90 days after the last dose of study treatment.
12. If a man, agrees to refrain from sperm donation throughout the study period and for a period of 90 days following the last dose of investigational medicinal product (IMP). Female subjects may not begin a cycle of ova donation or harvest throughout the study period and for a period of 90 days following the last dose of IMP.

Exclusion Criteria:

1. Presence of esophageal, gastroesophageal, or isolated gastric varices, based on an upper gastrointestinal (GI) esophagogastroduodenoscopy (EGD) exam conducted during Screening. Patients with portal hypertensive gastropathy could be enrolled.
2. History of hepatic cirrhosis decompensation including any episode of variceal bleeding, ascites not controlled by medication, spontaneous bacterial peritonitis or overt hepatic encephalopathy (West Haven grade ≥2 as assessed by the principal investigator), OR develops signs of hepatic cirrhosis decompensation during Screening.
3. Known or suspected abuse of alcohol (>20 g/day for women or >30 g/day for men [on average per day]), as per medical history. Significant alcohol consumption is defined as more than 20 grams per day in females and more than 30 grams per day in males. On average, a standard drink in the United States is considered to be 14 grams of alcohol, equivalent to 12 fluid ounces of regular beer (5% alcohol), 5 fluid ounces of table wine (12% alcohol), or 1.5 fluid ounces of 80 proof spirits (40% alcohol).
4. Alcohol dependence (ie, a score >8 on the Alcohol Use Disorders Identification Test)
5. Narcotics or any other drug abuse or dependence in the last 5 years
6. Prior trans-jugular intrahepatic portal-systemic (TIPS) shunt procedure
7. Documented causes of liver disease other than NASH, including but not restricted to:
   • Viral hepatitis, unless eradicated at least 3 years prior to Screening
     • acute hepatitis A infection (presence of hepatitis A immunoglobulin M [IgM] at Screening)
     • positive hepatitis B surface antigen
     • positive hepatitis C virus (HCV) ribonucleic acid (to be performed prior to randomization in case of positive HCV antibody)
   • Documented drug-induced liver disease
   • Alcoholic liver disease
   • Autoimmune hepatitis
   • Wilson’s disease
   • Hemochromatosis
   • Primary biliary cholangitis
   • Primary sclerosing cholangitis
   • Genetic hemochromatosis
   • History or planned liver transplantation
   • Alpha-1 antitrypsin deficiency

8. History of human immunodeficiency virus (HIV), or positive HIV test at Screening
9. Any of the following test or score:
   • serum alanine aminotransferase (ALT) > 5 × upper limit of normal (ULN)*
   • serum aspartate aminotransferase (AST) > 5 × ULN*
     • *Screening values will be obtained at SV1 and SV2 (which will be separated by 2 to 4 weeks). A second screening value that is >50% higher than the first value should prompt re-evaluation of the severity of the underlying liver disease and eligibility for this trial. If a transaminase level at SV2 is >33% different from the level at SV1, then additional measurements should be performed at SV3. In such cases, the baseline transaminase levels will be established for subjects using the mean value of 4 evaluations [ie, at SV1, SV2, SV3, and Baseline (ie, pre-dose during Visit 1)].
   • serum ALP > 2 × ULN
   • mean platelet count < 50,000/mm3
   • total bilirubin ≥ 2.0 mg/dL (subjects with a documented history of Gilbert’s syndrome can be enrolled if the direct bilirubin is within normal reference range)
   • model for end-stage liver disease (MELD) score ≥12
   • Child-Turcotte-Pugh (CTP) Score ≥7 Note: Following Phase 2b, subjects with CTP scores ≥7 may be enrolled if recommended* by the Data Safety Monitoring Board (DSMB) and approved by the Trial Steering Committee (TSC), based on the planned interim analysis (IA). [*based on DSMB review of preliminary results from a separate hepatic impairment clinical trial (Study GT-032) which is assessing belapectin safety and PK in cirrhotic subjects with CTP scores ≥7.
   • estimated glomerular filtration rate < 45 mL/min* *Note: per Modification of Diet in Renal Disease algorithm

10. Taking an angiotensin converting enzyme inhibitor, angiotensin II receptor blocker, or β-1 selective adrenergic receptor inhibitor, unless on a stable regimen for at least 3 months prior to Screening and no changes in the regimen are anticipated during the study. Subjects taking a non-selective beta blocker are not eligible to be enrolled (Investigators are encouraged to substitute another medication, if clinically warranted).
11. History of major surgery during Screening.
12. History of a solid organ transplant requiring immunosuppressive therapy.
13. History of bariatric surgery within 1 year of randomization, or plan to undergo bariatric surgery during the study.
14. Has positive screening test for illicit drugs of abuse at Screening.
15. Has participated in an investigational new drug study within 30 days or 5 half-lives whichever is longer, prior to randomization.
16. Has a history of malignancy within 5 years of randomization, except for basal cell carcinoma, squamous cell carcinoma, and adequately treated in situ uterine cervical cancer.
17. Has clinically significant cardiovascular disease (eg, uncontrolled hypertension, myocardial infarction, unstable angina), New York Heart Association Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring intervention (eg, pacemaker/ablation) or Grade II or greater peripheral vascular disease.
18. Has a history of clinically significant hematologic, renal, hepatic, pulmonary, neurological, psychiatric, gastrointestinal, systemic inflammatory, metabolic or endocrine disorder or any other condition that, in the opinion of the Investigator, renders the subject a poor candidate for inclusion into the study.
19. Has known allergies to the IMP or any of its excipients.
20. Has previously received belapectin within 6 months of randomization.
21. Is an employee or family member of the Investigator or study center personnel

Start Date: June 22, 2020

Projected End Date: December 2023

ClinicalTrials.gov Identifier: NCT04365868

Study Web Address for Potential Patients: https://galectintherapeutics.com/

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Study Title

The Effect of Semaglutide in Subjects With Non-cirrhotic Non-alcoholic Steatohepatitis

Protocol Name: ESSENCE
Protocol Number: NN9931-4553

Description: Semaglutide is a medicine studied in patients with NASH. Semaglutide is a well-known medicine, which is already used by doctors to treat type 2 diabetes in many countries.

Participants will either get semaglutide or a dummy medicine – which treatment participants get is decided by chance.

Participants will need to inject themselves with medicine under the skin. Participants will need to do this once a week.

The study will last for about 5 years. Participants will have up to 21 clinic visits and up to 9 phone calls with the clinical staff during the study. Some of the clinic visits may be spread over more than one day.

Women cannot take part in the study if they are pregnant, breast-feeding or plan to become pregnant during the study period.

Eligibility: 18 Years and older

Inclusion Criteria:

• Age above or equal to 18 years at the time of signing informed consent.
• Histological evidence of NASH (non-alcoholic steatohepatitis) based on a central pathologist evaluation of the baseline liver biopsy. The baseline liver biopsy can be a historical biopsy obtained within 180 days prior to screening visit (V1).
• Histological evidence of fibrosis stage 2 or stage 3 according to the NASH CRN (Clinical Research Network) classification based on a central pathologist evaluation of the baseline liver biopsy.
• A histological NAS (Non-alcoholic fatty liver disease Activity Score) above or equal to 4 with a score of 1 or more in both steatosis, lobular inflammation and hepatocyte ballooning based on a central pathologist evaluation of the baseline liver biopsy.

Exclusion Criteria:

• Positive HBsAg (hepatitis B surface antigen), positive anti-HIV (human immunodeficiency virus), positive HCV-RNA (Hepatitis C virus RNA) at screening or any known presence of HCV RNA (ribonucleic acid) or HBsAg within 2 years of screening (V2A).
• Documented causes of chronic liver disease other than Non-Alcoholic Fatty Liver Disease NAFLD.
• Presence or history of ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis or liver transplantation at randomisation.
• Known or suspected excessive consumption of alcohol (greater than 20 g/day for women or greater than 30 g/day for men) or alcohol dependence (assessed by the Alcohol Use Disorders Identification Test (AUDIT questionnaire).
• Treatment with vitamin E (at doses above or equal to 800 IU/day) or pioglitazone or medications approved for treatment of NASH which has not been at a stable dose in the opinion of the investigator in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until screening.
• Treatment with GLP-1 RAs (glucagon-like peptide-1 receptor agonist) in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, any treatment with GLP-1 RAs from time of biopsy until screening.
• Treatment with glucose lowering agent(s) (other than GLP-1 RAs), lipid lowering medication or weight loss medication not stable in the opinion of the investigator in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until screening.

Start Date: April 1, 2021

Projected End Date: May 26, 2028

ClinicalTrials.gov Identifier: NCT04822181

Study Web Address for Potential Patients: https://www.novonordisk-trials.com/en/