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

NCT05402371 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HEPA-CRV431-207
• Study Type: interventional
• Target: 120
• Locations: 3 countries
• Sites: 41

Brief Summary

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.

Conditions

Nonalcoholic Steatohepatitis (NASH); Fibrosis, Liver; NAFLD

Keywords

Nonalcoholic Steatohepatitis; NAFLD; NASH; liver fibrosis

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects with improvement in fibrosis by at least 1 stage (NASH CRN system) OR NASH resolution without worsening of fibrosis.

  Efficacy

  dosing period of 1 year with 1 month observation and follow up period

Secondary Outcomes (6)

• Proportion of subjects with improvement in fibrosis by at least 1 stage (NASH CRN system), regardless of effect on NASH.

  dosing period of 1 year with 1 month observation and follow up period

• Proportion of subjects with improvement in fibrosis by at least 2 stages (NASH CRN system), regardless of effect on NASH.

  dosing period of 1 year with 1 month observation and follow up period

• Proportion of subjects with improvement in fibrosis by at least 2 stages (NASH CRN system) AND no worsening of NASH.

  dosing period of 1 year with 1 month observation and follow up period

• Change from baseline in ALT.

  dosing period of 1 year with 1 month observation and follow up period

• Change from baseline in AST.

  dosing period of 1 year with 1 month observation and follow up period

Study Arms (4)

Cohort A: Rencofilstat 75 mg

EXPERIMENTAL

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

Drug: Rencofilstat

Cohort B: Rencofilstat 150 mg

EXPERIMENTAL

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

Drug: Rencofilstat

Cohort C: Rencofilstat 225 mg

EXPERIMENTAL

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

Drug: Rencofilstat

Cohort D: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Rencofilstat DRUG

Rencofilstat soft gel capsule

Also known as: CRV431

Cohort A: Rencofilstat 75 mg; Cohort B: Rencofilstat 150 mg; Cohort C: Rencofilstat 225 mg

Placebo DRUG

placebo soft gel capsule

Cohort D: Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between 18 and 75 years of age (inclusive).
• Capable of giving written informed consent and able to effectively communicate with the investigator and study personnel.
• 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).
• 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).

You may not qualify if:

• Pregnant or breastfeeding or planning to become pregnant during the study period.
• Known allergy to Rencofilstat, cyclosporine, or any of their inactive ingredients.
• Subjects with suspected and symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection identified prior to first dose.
• 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).
• Subjects with uncontrolled or unstable cardiac arrhythmias:
• Severe conduction disturbance (e.g., second-degree or third-degree AV block).
• History of congenital long QT syndrome, congenital short QT syndrome, Torsades de Pointes, or Wolff Parkinson White syndrome.
• Subjects with transaminases \>5 x upper limit of normal (ULN).
• Subjects with ALP \>2 x ULN.
• Subjects with total serum bilirubin \>1.5 x ULN.
• Subjects with a platelet count \<100,000/mm3.
• Subjects with an INR ≥ 1.3 in the absence of anticoagulants.
• Subjects with albumin \<3.5 g/dL.
• Model for End-Stage Liver Disease (MELD) score \>12, unless due to an alternate etiology such as therapeutic anticoagulation.
• 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.

Sponsors & Collaborators

• Hepion Pharmaceuticals, Inc.: lead

Study Sites (41)

Medical Affiliated Research Center

Huntsville, Alabama, 35801, United States

Location

Arizona Liver Health-Chandler

Chandler, Arizona, 85224, United States

Location

Arizona Liver Health

Peoria, Arizona, 85381, United States

Location

Adobe Clinical Research, LLC

Tucson, Arizona, 85712, United States

Location

Arizona Liver Health-Tuscon

Tucson, Arizona, 85712, United States

Location

Preferred Research Partners, Inc.

Little Rock, Arkansas, 72211, United States

Location

Arkansas Gastroenterology

North Little Rock, Arkansas, 72117, United States

Location

National Research Institute

Huntington Park, California, 90255, United States

Location

National Research Institute

Los Angeles, California, 90057, United States

Location

National Research Institute

Panorama City, California, 91402, United States

Location

National Research Institute

Santa Ana, California, 92704, United States

Location

Synergy Healthcare, LLC

Bradenton, Florida, 34208, United States

Location

Tampa Bay Medical Research, Inc.

Clearwater, Florida, 33761, United States

Location

Top Medical Research, Inc.

Cutler Bay, Florida, 33189, United States

Location

Integrity Clinical Research, LLC

Doral, Florida, 33166, United States

Location

Evolution Clinical Trials, Inc.

Hialeah Gardens, Florida, 33016, United States

Location

Borland Groover Clinical Research

Jacksonville, Florida, 32256, United States

Location

Ocala GI Research

Lady Lake, Florida, 32159, United States

Location

Accel Research Sites-Lakeland CRU

Lakeland, Florida, 33803, United States

Location

Future Care Solutions, LLC

Miami, Florida, 33165, United States

Location

Entrust Clinical Research

Miami, Florida, 33176, United States

Location

United Reseach Group

Miami, Florida, 33186, United States

Location

Omega Research Consultants, LLC

Orlando, Florida, 32810, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Covenant Research and Clinics

Sarasota, Florida, 34240, United States

Location

Southeast Clinical Research Center

Dalton, Georgia, 30720, United States

Location

Gastrointestinal Specialists of Georgia, PC

Marietta, Georgia, 30060, United States

Location

Digestive Research Alliance of Michiana, LLC

South Bend, Indiana, 46635, United States

Location

Delta Research Partners

Bastrop, Louisiana, 71220, United States

Location

Mid-Atlantic GI Research, LLC

Greenbelt, Maryland, 20770, United States

Location

AIG Digestive Disease Research, LLC

Florham Park, New Jersey, 07932, United States

Location

Pinnacle Clinical Research-Austin

Austin, Texas, 78757, United States

Location

South Texas Research Institute

Brownsville, Texas, 78520, United States

Location

South Texas Research Institute

Edinburg, Texas, 78539, United States

Location

LinQ Research, LLC

Pearland, Texas, 77584, United States

Location

Pinnacle Clinical Research-San Antonio

San Antonio, Texas, 78229, United States

Location

Bon Secours Liver Institute of Hampton Roads

Newport News, Virginia, 23602, United States

Location

GI Select Health Research, LLC

Richmond, Virginia, 23236, United States

Location

Velocity Clinical Spokane

Spokane, Washington, 99202, United States

Location

Hopital du Haut Leveque

Pessac, 33604, France

Location

Centro de Investigacion y Gastroenterologia SC

Mexico City, 06700, Mexico

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Liver Cirrhosis

Interventions

CRV-431

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Stephen Harrison, MD

  Pinnacle Clinical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: blinded, placebo controlled, randomized

Study Record Dates

• First Submitted: May 20, 2022
• First Posted: June 2, 2022
• Study Start: October 15, 2022
• Primary Completion: May 1, 2025
• Study Completion: September 1, 2025
• Last Updated: May 3, 2024

Record last verified: 2024-05

Locations

ME (1); US (39); FR (1)