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

NASH - Nonalcoholic Steatohepatitis Clinical Trial

— AMBITION  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04480710
• Other study ID #: HEPA-CRV431-201
• Status: Completed
• Phase: Phase 2
• Start date: June 23, 2020
• Est. completion date: October 30, 2021

Study information

• Verified date: June 2022
• Source: Hepion Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: October 30, 2021
• Est. primary completion date: June 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fatty Liver
• Fibrosis, Liver
• Liver Cirrhosis
• Liver Diseases
• NAFLD - Nonalcoholic Fatty Liver Disease
• NASH - Nonalcoholic Steatohepatitis
• Non-alcoholic Fatty Liver Disease

Intervention

Drug:
• CRV431 75mg
1 x 75mg softgel capsule
• Placebo (1 softgel)
1 x placebo softgel capsule
• CRV431 225mg
3 x 75mg softgel capsule
• Placebo (3 softgels)
3 x placebo softgel capsule

Locations

Country	Name	City	State
Puerto Rico	FDI Clinical Research	San Juan
United States	Aventiv Research Inc.	Columbus	Ohio
United States	Gastrointestinal Specialists of Georgia	Marietta	Georgia
United States	La Salud Research, Inc.	Miami	Florida
United States	Conquest Clinical Research	Orange	California
United States	Progressive Medical Research	Port Orange	Florida
United States	Alliance Clinical Research	Poway	California
United States	Pinnacle Research Group	San Antonio	Texas
United States	Quality Research Inc.	San Antonio	Texas
United States	Covenant Research, LLC.	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hepion Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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
Primary	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
Primary	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.