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

AMBITION: A Phase 2A, Multiple-Center, Single-Blind, Placebo-Controlled Study To Evaluate The Safety and Tolerability of CRV431 Dosed Once Daily in NASH Induced F2 and F3 Subjects

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

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • FDI Clinical Research
• United States
  • California
    • Orange, California, United States, 92866
      • Conquest Clinical Research
    • Poway, California, United States, 92064
      • Alliance Clinical Research
  • Florida
    • Miami, Florida, United States, 33155
      • La Salud Research, Inc.
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Sarasota, Florida, United States, 34249
      • Covenant Research, LLC.
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Aventiv Research Inc.
  • Texas
    • San Antonio, Texas, United States, 78209
      • Quality Research Inc.
    • San Antonio, Texas, United States, 78229
      • Pinnacle Research Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CRV431 75mg; CRV431, softgel capsule, 75mg, QD, 28 days, fasted conditions	Drug: CRV431 75mg; 1 x 75mg softgel capsule
PLACEBO_COMPARATOR: Placebo, 75mg; Placebo, softgel capsule, QD, 28 days, fasted conditions	Drug: Placebo (1 softgel); 1 x placebo softgel capsule
EXPERIMENTAL: CRV431 225mg; CRV431, softgel capsule, 225mg, QD, 28 days, fasted conditions	Drug: CRV431 225mg; 3 x 75mg softgel capsule
PLACEBO_COMPARATOR: Placebo, 225mg; CRV431, 3 softgel capsules, 225mg, QD, 28 days, fasted conditions	Drug: Placebo (3 softgels); 3 x placebo softgel capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Safety and Tolerability Events of CRV431 Versus Placebo.	Number of adverse events, serious adverse events, and clinical laboratory abnormalities.	Time from informed consent to study day 42.
Tmax, of Once Daily (QD) 75mg and 225mg mg Doses of CRV431 is Presumed Non-alcoholic Steatohepatitis F2/F3 Fibrosis Subjects.	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.	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.	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.	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.	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.	Timepoints for data collection include 0, 2.0 hours, 4.0 hours, 8 hours on both Day 1 and Day 28.

Collaborators and Investigators

• Sponsor: Hepion Pharmaceuticals, Inc.
• Investigators: Study Director: Carlos Canizares, R.Ph., Hepion Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 23, 2020
• Primary Completion (ACTUAL): June 29, 2021
• Study Completion (ACTUAL): October 30, 2021

Study Registration Dates

• First Submitted: July 9, 2020
• First Submitted That Met QC Criteria: July 20, 2020
• First Posted (ACTUAL): July 21, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 15, 2022
• Last Update Submitted That Met QC Criteria: July 13, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Anti-fibrotic
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Fibrosis; Liver Diseases; Fatty Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: HEPA-CRV431-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No