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

Hepion Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: NAFLD - Nonalcoholic Fatty Liver Disease; Fibrosis, Liver; NASH - Nonalcoholic Steatohepatitis

Treatments: Drug: Placebo (3 softgels); Drug: CRV431 225mg; Drug: CRV431 75mg; Drug: Placebo (1 softgel)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04480710

HEPA-CRV431-201

Details and patient eligibility

About

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

Full 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.

Enrollment: 47 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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47 participants in 4 patient groups, including a placebo group

CRV431 75mg

Experimental group

Description:

CRV431, softgel capsule, 75mg, QD, 28 days, fasted conditions

Treatment:

Drug: CRV431 75mg

Placebo, 75mg

Placebo Comparator group

Description:

Placebo, softgel capsule, QD, 28 days, fasted conditions

Treatment:

Drug: Placebo (1 softgel)

CRV431 225mg

Experimental group

Description:

CRV431, softgel capsule, 225mg, QD, 28 days, fasted conditions

Treatment:

Drug: CRV431 225mg

Placebo, 225mg

Placebo Comparator group

Description:

CRV431, 3 softgel capsules, 225mg, QD, 28 days, fasted conditions

Treatment:

Drug: Placebo (3 softgels)