A Study of CRV431 Dosed Once Daily in NASH Induced F2 and F3 Subjects

Phase 2

Completed

• Conditions: Fibrosis, Liver; NAFLD - Nonalcoholic Fatty Liver Disease; NASH - Nonalcoholic Steatohepatitis
• Interventions: Drug: Placebo (3 softgels); Drug: CRV431 75mg; Drug: Placebo (1 softgel); Drug: CRV431 225mg

• Registration Number: NCT04480710
• Lead Sponsor: Hepion Pharmaceuticals, Inc.

Brief Summary

This is a randomized, single-blind, placebo-controlled, once daily (QD) dose study of CRV431 in presumed NASH F2/F3 subjects.

Detailed Description

This is a randomized, single-blind, placebo-controlled, once daily (QD) dose study of CRV431 in presumed NASH F2/F3 subjects. Study will evaluate the safety and tolerability of a once daily 75mg dose and 225mg of CRV431 compared to placebo over 28 days of dosing. Pharmacokinetic parameters of CRV431 and its major metabolites and fraction unbound will also be evaluated. Non-invasive antifibrotic bio-markers will be collected and quantified from presumed NASH F2/F3 subjects dosed with 75mg CRV431 or placebo.

Study Timeline

• Study Start: 2020-06-23
• Study First Submitted: 2020-07-09
• Study First Submitted QC: 2020-07-20
• Study First Posted: 2020-07-21
• Primary Completion: 2021-06-29
• Study Completion: 2021-10-30
• Results First Submitted: 2022-05-02
• Status Verified: 2022-06
• Results First Submitted QC: 2022-07-13
• Last Update Submitted: 2022-07-13
• Results First Posted: 2022-07-15
• Last Update Posted: 2022-07-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 47

Inclusion Criteria

• 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.
• Presumed F2/F3 NASH to include: AST >20 IU/L, Pro-C3 >15.5 ng/mL, enhanced liver fibrosis (ELF) score >9.8, and FibroScan >8.5 kPa values.

Key

Exclusion Criteria

• Pregnant or breastfeeding or planning to become pregnant during the study period.
• Known allergy to CRV431, cyclosporine, or any of their inactive ingredients.
• Positive test for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCVAb) or human immunodeficiency virus antibodies (HIVAb).
• Well documented causes of chronic liver disease according to standard diagnostic procedures to include any history or presence of decompensated cirrhosis.
• Subjects with a platelet count <150,000/mL.
• Subjects with hemoglobin A1c(HbA1c) >9.5%.
• Weight loss of more than 5% within 3 months prior to randomization.
• Subjects with a blood pressure to include a systolic pressure >150 or a diastolic pressure >90.
• At Screening, an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 mL (calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] method) and/or a Kidney Disease Improving Global Outcomes (KDIGO) category of >G2.
• Subjects with a history of organ transplantation. Corneal transplantation will be allowed.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo, 225mg	Placebo (3 softgels)	CRV431, 3 softgel capsules, 225mg, QD, 28 days, fasted conditions
CRV431 75mg	CRV431 75mg	CRV431, softgel capsule, 75mg, QD, 28 days, fasted conditions
Placebo, 75mg	Placebo (1 softgel)	Placebo, softgel capsule, QD, 28 days, fasted conditions
CRV431 225mg	CRV431 225mg	CRV431, softgel capsule, 225mg, QD, 28 days, fasted conditions

Primary Outcome Measures

Name	Time	Method
Number of Safety and Tolerability Events of CRV431 Versus Placebo.	Time from informed consent to study day 42.	Number of adverse events, serious adverse events, and clinical laboratory abnormalities.
Tmax, of Once Daily (QD) 75mg and 225mg mg Doses of CRV431 is Presumed Non-alcoholic Steatohepatitis F2/F3 Fibrosis Subjects.	Day 1 and Day 28	The Tmax value is defined as time to reach maximum whole blood concentration. Each value is a median for the cohort along with the standard deviation presented in hours for Day 1 and Day 28.
AUC 0-last, of Once Daily (QD) 75mg and 225mg mg Doses of CRV431 in Presumed Non-alcoholic Steatohepatitis F2/F3 Fibrosis Subjects.	Timepoints for data collection include 0, 2.0 hours, 4.0 hours, 8 hours on both Day 1 and Day 28.	The AUC 0-last value is defined as the area under the whole blood concentration time curve from time 0 to the time of the last measurable concentration. Each value is a geometric mean for the cohort along with the standard deviation for Day 1 and Day 28.
Cmax, of Once Daily (QD) 75mg and 22mg mg Doses of CRV431 is Presumed Non-alcoholic Steatohepatitis F2/F3 Fibrosis Subjects.	Day 1 and Day 28	The Cmax value is defined as the maximum whole blood concentration presented as ng/mL. Each value is a geometric mean for the cohort along with the standard deviation for Day 1 and Day 28.

Trial Locations

Locations (10)

La Salud Research, Inc.; 🇺🇸 Miami, Florida, United States

Gastrointestinal Specialists of Georgia; 🇺🇸 Marietta, Georgia, United States

Conquest Clinical Research; 🇺🇸 Orange, California, United States

FDI Clinical Research; 🇵🇷 San Juan, Puerto Rico

Quality Research Inc.; 🇺🇸 San Antonio, Texas, United States

Pinnacle Research Group; 🇺🇸 San Antonio, Texas, United States

Aventiv Research Inc.; 🇺🇸 Columbus, Ohio, United States

Covenant Research, LLC.; 🇺🇸 Sarasota, Florida, United States

Alliance Clinical Research; 🇺🇸 Poway, California, United States

Progressive Medical Research; 🇺🇸 Port Orange, Florida, United States