A Study to Evaluate the Efficacy and Safety of Rencofilstat in Subjects With NASH and Advanced Liver Fibrosis

NCT ID: NCT05402371

Last Updated: 2024-05-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-15

Study Completion Date

2025-09-30

Brief Summary

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This is a randomized, double-blind, placebo-controlled, parallel-dosing, multi-center study to evaluate the efficacy and safety of Rencofilstat as evidenced by histopathological improvements in fibrosis in adult NASH subjects with F2 or F3 fibrosis (NASH CRN system). Antifibrotic biomarker activity will be evaluated on an exploratory basis.

Detailed Description

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This is a randomized, double-blind, placebo-controlled, parallel-dosing, multi-center study to evaluate the efficacy and safety of Rencofilstat as evidenced by histopathological improvements in fibrosis in adult NASH subjects with F2 or F3 fibrosis (NASH CRN system). Antifibrotic biomarker activity will be evaluated on an exploratory basis.

This study consists of 3 phases: (i) Screening and Randomization; (ii) treatment; and (iii) follow up. During Screening, each subject will provide informed consent prior to starting any study specific procedures. The randomization of the F2/F3 NASH subjects will be performed in a 1:1:1:1 ratio between Rencofilstat 75mg, Rencofilstat 150mg, Rencofilstat 225mg, and matching placebo. Subjects will be stratified by presence or absence of Type 2 diabetes, fibrosis stage and a maximum of 34 F2 subjects in each cohort.

Conditions

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Nonalcoholic Steatohepatitis (NASH) Fibrosis, Liver NAFLD

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

blinded, placebo controlled, randomized
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
double blind

Study Groups

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Cohort A: Rencofilstat 75 mg

Eighty-four (84) biopsy-proven NASH F2/F3 subjects to complete study on Rencofilstat 75 mg daily.

Group Type EXPERIMENTAL

Rencofilstat

Intervention Type DRUG

Rencofilstat soft gel capsule

Cohort B: Rencofilstat 150 mg

Eighty-four (84) biopsy-proven NASH F2/F3 subjects to complete study on Rencofilstat 150 mg daily.

Group Type EXPERIMENTAL

Rencofilstat

Intervention Type DRUG

Rencofilstat soft gel capsule

Cohort C: Rencofilstat 225 mg

Eighty-four (84) biopsy-proven NASH F2/F3 subjects to complete study on Rencofilstat 225 mg daily.

Group Type EXPERIMENTAL

Rencofilstat

Intervention Type DRUG

Rencofilstat soft gel capsule

Cohort D: Placebo

Eighty-four (84) biopsy-proven NASH F2 / F3 subjects to complete study on matching placebo.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

placebo soft gel capsule

Interventions

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Rencofilstat

Rencofilstat soft gel capsule

Intervention Type DRUG

Placebo

placebo soft gel capsule

Intervention Type DRUG

Other Intervention Names

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CRV431

Eligibility Criteria

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Inclusion Criteria

1. Male or female between 18 and 75 years of age (inclusive).
2. Capable of giving written informed consent and able to effectively communicate with the investigator and study personnel.
3. Histologic evidence of NASH based on central readings of the screening biopsy obtained no more than 6 months before Screening defined by presence of all 3 key histological features, Nonalcoholic Fatty Liver Disease Activity Score (NAS) ≥ 4 with at least 1 point each in lobular inflammation and hepatocyte ballooning.

a. Historical biopsy may be substituted for Screening biopsy to determine eligibility if the following are met: i. Historical biopsy was obtained no more than 180 ± 5 days prior to the first day of Screening.

ii. Hepatic tissue or slides are available for central histologic evaluation. iii. No new therapeutic intervention for NASH was made 90 days prior to screening (e.g., obeticholic acid, vitamin E ≥ 400 IU/day, pioglitazone, incretins \[e.g., liraglutide, semaglutide\], sodium-glucose cotransporter-2 \[SGLT2\] inhibitors).

iv. Subjects must have been metabolically stable since the biopsy (no significant weight loss ≥ 7% of body weight, no major deterioration of glycemic control, and no introduction of new or investigational drugs for the treatment of Type 2 Diabetes).
4. Histologic liver fibrosis stage 2 or 3 as defined by the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) scoring of liver fibrosis based on central reading of the Screening biopsy (refer to criteria 4a regarding use of a historical biopsy as a substitute for the Screening biopsy).
5. Blood pressure up to 160/100 mmHg; potential subjects who meet other eligibility requirements, but who have out of range blood pressure measurements deemed to be not clinically significant by the investigator, may still be considered for study inclusion.

4. Subjects with suspected and symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection identified prior to first dose.
5. Subjects with a history of clinically significant acute cardiac events within 30 days prior to Screening such as stroke, transient ischemic attack, or coronary heart disease (angina pectoris requiring therapy, myocardial infarction, revascularization procedures with left ventricular ejection fraction \[LVEF\] \<50% as determined by previous echocardiography or multiple gated acquisition \[MUGA\] scan).
6. Subjects with uncontrolled or unstable cardiac arrhythmias:

1. Severe conduction disturbance (e.g., second-degree or third-degree AV block).
2. History of congenital long QT syndrome, congenital short QT syndrome, Torsades de Pointes, or Wolff Parkinson White syndrome.
7. Subjects with transaminases \>5 x upper limit of normal (ULN).
8. Subjects with ALP \>2 x ULN.
9. Subjects with total serum bilirubin \>1.5 x ULN.
10. Subjects with a platelet count \<100,000/mm3.
11. Subjects with an INR ≥ 1.3 in the absence of anticoagulants.
12. Subjects with albumin \<3.5 g/dL.
13. Model for End-Stage Liver Disease (MELD) score \>12, unless due to an alternate etiology such as therapeutic anticoagulation.
14. Current or previous (within the past 6 months) Child-Pugh (CP) score ≥ 7 for F2 or F3 subjects, unless due to an alternative etiology such as Gilbert's syndrome or therapeutic anticoagulation.
15. An estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] method).
16. Subjects with hemoglobin A1c (HbA1c) \>9.5%.
17. Subjects with any history or presence of decompensated cirrhosis including ascites, hepatic encephalopathy or variceal bleeding.
18. Other well documented causes of chronic liver disease according to standard diagnostic procedures including, but not restricted to:

1. Suspicion of drug-induced liver disease.
2. Alcoholic liver disease.
3. Autoimmune hepatitis.
4. Wilson's disease.
5. Primary biliary cholangitis, primary sclerosing cholangitis.
6. Genetic hemochromatosis (Homozygosity for C282Y or C282Y/H63D compound heterozygote).
7. Known or suspected hepatocellular carcinoma (HCC).
8. History or planned liver transplant.
9. Clinical evidence of portal hypertension such as esophageal varices, ascites, history of hepatic encephalopathy, or splenomegaly.
19. History of hepatic decompensating events or subjects who develop manifestations of hepatic decompensation between screening and enrollment should not be randomized, inclusive of new or worsening jaundice and ascites, new esophageal varices, etc.
20. Subjects with Type 2 diabetes who have recent (\< 3 months) changes in medication class or dose of the following antidiabetic medications: Glucagon-like-peptide-1 (GLP-1) receptor agonist, dipeptidyl peptidase-4 (DPP-4) inhibitor, sodium/glucose cotransporter 2 (SGLT2) inhibitor, thiazolidinediones (TZD).
21. Received an investigational drug or investigational vaccine or used an investigational medical device within 60 days prior to first dose of study drug.
22. Received any investigation products being evaluated for the treatment of liver fibrosis or NASH in the 6 months prior to the Screening liver biopsy.
23. Inability to undergo MRE procedure due to unremovable metal or foreign object(s) or contraindication for any other reason including but not limited to pacemaker, shrapnel injury, extensive tattoos, severe claustrophobia, ear (cochlea) implant.

Exclusion Criteria

1. Pregnant or breastfeeding or planning to become pregnant during the study period.
2. Known allergy to Rencofilstat, cyclosporine, or any of their inactive ingredients.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hepion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stephen Harrison, MD

Role: PRINCIPAL_INVESTIGATOR

Pinnacle Clinical Research

Locations

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Medical Affiliated Research Center

Huntsville, Alabama, United States

Site Status

Arizona Liver Health-Chandler

Chandler, Arizona, United States

Site Status

Arizona Liver Health

Peoria, Arizona, United States

Site Status

Adobe Clinical Research, LLC

Tucson, Arizona, United States

Site Status

Arizona Liver Health-Tuscon

Tucson, Arizona, United States

Site Status

Preferred Research Partners, Inc.

Little Rock, Arkansas, United States

Site Status

Arkansas Gastroenterology

North Little Rock, Arkansas, United States

Site Status

National Research Institute

Huntington Park, California, United States

Site Status

National Research Institute

Los Angeles, California, United States

Site Status

National Research Institute

Panorama City, California, United States

Site Status

National Research Institute

Santa Ana, California, United States

Site Status

Synergy Healthcare, LLC

Bradenton, Florida, United States

Site Status

Tampa Bay Medical Research, Inc.

Clearwater, Florida, United States

Site Status

Top Medical Research, Inc.

Cutler Bay, Florida, United States

Site Status

Integrity Clinical Research, LLC

Doral, Florida, United States

Site Status

Evolution Clinical Trials, Inc.

Hialeah Gardens, Florida, United States

Site Status

Borland Groover Clinical Research

Jacksonville, Florida, United States

Site Status

Ocala GI Research

Lady Lake, Florida, United States

Site Status

Accel Research Sites-Lakeland CRU

Lakeland, Florida, United States

Site Status

Future Care Solutions, LLC

Miami, Florida, United States

Site Status

Entrust Clinical Research

Miami, Florida, United States

Site Status

United Reseach Group

Miami, Florida, United States

Site Status

Omega Research Consultants, LLC

Orlando, Florida, United States

Site Status

Progressive Medical Research

Port Orange, Florida, United States

Site Status

Covenant Research and Clinics

Sarasota, Florida, United States

Site Status

Southeast Clinical Research Center

Dalton, Georgia, United States

Site Status

Gastrointestinal Specialists of Georgia, PC

Marietta, Georgia, United States

Site Status

Digestive Research Alliance of Michiana, LLC

South Bend, Indiana, United States

Site Status

Delta Research Partners

Bastrop, Louisiana, United States

Site Status

Mid-Atlantic GI Research, LLC

Greenbelt, Maryland, United States

Site Status

AIG Digestive Disease Research, LLC

Florham Park, New Jersey, United States

Site Status

Pinnacle Clinical Research-Austin

Austin, Texas, United States

Site Status

South Texas Research Institute

Brownsville, Texas, United States

Site Status

South Texas Research Institute

Edinburg, Texas, United States

Site Status

LinQ Research, LLC

Pearland, Texas, United States

Site Status

Pinnacle Clinical Research-San Antonio

San Antonio, Texas, United States

Site Status

Bon Secours Liver Institute of Hampton Roads

Newport News, Virginia, United States

Site Status

GI Select Health Research, LLC

Richmond, Virginia, United States

Site Status

Velocity Clinical Spokane

Spokane, Washington, United States

Site Status

Hopital du Haut Leveque

Pessac, , France

Site Status

Centro de Investigacion y Gastroenterologia SC

Mexico City, , Mexico

Site Status

Countries

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United States France Mexico

Other Identifiers

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HEPA-CRV431-207

Identifier Type: -

Identifier Source: org_study_id

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