A Study to Evaluate the Safety and Efficacy of Rencofilstat in Adult Subjects With NASH F3

NCT ID: NCT05461105

Last Updated: 2024-06-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-15
• Study Completion Date: 2023-07-07

Brief Summary

This is a randomized, open-label, parallel-dosing, multi-center study to evaluate the safety and efficacy of rencofilstat as evidenced by assessing changes in the HepQuant Shunt Disease Severity Index Score (DSI), safety labs, and clinical events in adult NASH subjects with compensated Fibrosis stage F 2/3. Antifibrotic biomarker activity will be evaluated on an exploratory basis.

Detailed Description

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 NASH F3 subjects will be performed in a 1:1:1 ratio between rencofilstat 75 mg, rencofilstat 150 mg, and rencofilstat 225 mg. During the treatment period, randomized subjects will be provided the treatment and assessments to monitor safety, tolerability and efficacy. All subjects will receive study drug in the morning. Prior to dosing, subjects can have a light breakfast, avoiding high fat meals. In the follow up phase, investigational product (IP) will be discontinued followed by 14 days of safety follow-up.

Conditions

NASH With Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A: rencofilstat 75 mg

1 rencofilstat 75 mg softgel capsule, 75 mg daily dose, QD 120 days

Group Type: EXPERIMENTAL

rencofilstat, 75 mg

Intervention Type: DRUG

1 softgel capsule

Cohort B: rencofilstat 150 mg

2 rencofilstat 75 mg softgel capsules, 150 mg daily dose, QD 120 days

Group Type: EXPERIMENTAL

rencofilstat, 150mg

Intervention Type: DRUG

2 softgel capsules

Cohort C: rencofilstat 225 mg

3 rencofilstat 75 mg softgel capsules, 225 mg daily dose, QD 120 days

Group Type: EXPERIMENTAL

rencofilstat, 225 mg

Intervention Type: DRUG

3 softgel capsules

Interventions

rencofilstat, 75 mg

1 softgel capsule

Intervention Type: DRUG

rencofilstat, 150mg

2 softgel capsules

Intervention Type: DRUG

rencofilstat, 225 mg

3 softgel capsules

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female between 18 and 75 years of age (inclusive).

2. BMI above 25.0 kg/m2

3. Biopsy confirmed NASH with histologic liver fibrosis stage 3 as defined by the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) scoring of liver fibrosis based on available historical biopsy report if the following are met:

i. Historical biopsy was obtained no more than 6 months (180 ± 5 days) prior to the first day of Screening. ii. No new therapeutic intervention for NASH of at least 2 or more weeks was made during the preceding 3-month (90-day) period (e.g., vitamin E ≥ 400 IU/day, pioglitazone, or incretins [e.g., liraglutide, semaglutide]). Subjects may be treated with vitamin E or pioglitazone as long as such subjects are maintained on a stable dose for 3 months prior to randomization, and the dose should be held constant during the trial.

4. Subjects without historical biopsy will be eligible for inclusion if their AGILE 3+ score using the FibroScan Diagnostic App is ≥0.53. The AGILE 3+ score is composed of: FibroScan fibrosis score, laboratory values (AST, ALT, Platelets), and clinical parameters (Age, Sex, Diabetes status) to calculate the AGILE 3+ score.

2. Subjects with symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection identified during the screening period.

3. At screening, subjects with uncontrolled hypertension (either treated or untreated) defined as a systolic blood pressure >160mmHg or a diastolic blood pressure of >110mmHG.

4. Subjects on either a non-selective beta blocker or an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) who are unwilling/unable to delay taking their normal dose the morning of HepQuant testing.

5. Subjects with transaminases >5 x upper limit of normal (ULN).

6. Subjects with ALP >2 x ULN.

7. Subjects with total serum bilirubin >1.5 x ULN, unless the subject has Gilbert's Syndrome, in which case the subject can be enrolled provided the direct bilirubin is within 30% of the total bilirubin.

8. Subjects with a platelet count <140,000/mm3.

9. Subjects with an INR ≥ 1.3 in the absence of anticoagulants.

10. Subjects with albumin <3.5 g/dL.

11. Model for End-Stage Liver Disease (MELD) score >12, unless due to an alternate etiology such as therapeutic anticoagulation or Gilbert's.

12. An estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] method).

13. Subjects with hemoglobin A1c (HbA1c) >9.5%.

14. Other well documented causes of chronic liver disease according to standard diagnostic procedures.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hepion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Arizona Liver Health-Chandler

Chandler, Arizona, United States

Arizona Liver Health-Glendale

Peoria, Arizona, United States

Adobe Clinical Research, LLC

Tucson, Arizona, United States

Arizona Liver Health-Tucson

Tucson, Arizona, United States

Velocity Clinical Research-Chula Vista

Chula Vista, California, United States

Velocity Clinical Research-San Diego

La Mesa, California, United States

Synergy Healthcare, LLC

Bradenton, Florida, United States

Covenant Metabolic Specialists-Fort Myers

Fort Myers, Florida, United States

Evolution Clinical Trials, Inc.

Hialeah Gardens, Florida, United States

Progressive Medical Research

Port Orange, Florida, United States

Covenant Metabolic Specialists-Sarasota

Sarasota, Florida, United States

Clinical Research Institute of Michigan

Chesterfield, Michigan, United States

Coastal Reseach Institute

Fayetteville, North Carolina, United States

Optimed Research

Columbus, Ohio, United States

Clinical Research Institute of Ohio

Westlake, Ohio, United States

Pinnacle Clinical Research-Austin

Austin, Texas, United States

Apex Mobile Clinical Research

Bellaire, Texas, United States

South Texas Research Institute

Edinburg, Texas, United States

Pinnacle Clinical Research-Georgetown

Georgetown, Texas, United States

Pinnacle Clinical Research-San Antonio

San Antonio, Texas, United States

Countries

United States

References

Harrison SA, Mayo P, Hobbs T, Zhao C, Canizares C, Foster R, McRae MP, Helmke SM, Everson GT. Rencofilstat Treatment Improves Liver Function in MASH With Advanced Fibrosis as Quantified by HepQuant DuO. Liver Int. 2025 Mar;45(3):e70036. doi: 10.1111/liv.70036.

Reference Type: DERIVED

PMID: 39982177 (View on PubMed)

Other Identifiers

HEPA-CRV431-210

Identifier Type: -

Identifier Source: org_study_id