Clinical Research

Furthering science, research & medical developments.

Florida Medical Clinic Orlando Health 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

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/

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

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

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

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

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 2024

ClinicalTrials.gov Identifier: NCT04365868

Study Web Address for Potential Patients: N/A

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/