Title
A Study of CRV431 Dosed Once Daily in NASH Induced F2 and F3 Subjects
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
Phase
Phase 2Lead Sponsor
Hepion Pharmaceuticals, Inc.Study Type
InterventionalStatus
Completed Results PostedIndication/Condition
NASH - Nonalcoholic Steatohepatitis Fibrosis, Liver NAFLD - Nonalcoholic Fatty Liver DiseaseIntervention/Treatment
crv431 ...Study Participants
47This is a randomized, single-blind, placebo-controlled, once daily (QD) dose study of CRV431 in presumed NASH F2/F3 subjects.
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.
1 x 75mg softgel capsule
1 x placebo softgel capsule
3 x 75mg softgel capsule
3 x placebo softgel capsule
CRV431, softgel capsule, 75mg, QD, 28 days, fasted conditions
Placebo, softgel capsule, QD, 28 days, fasted conditions
CRV431, softgel capsule, 225mg, QD, 28 days, fasted conditions
CRV431, 3 softgel capsules, 225mg, QD, 28 days, fasted conditions
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.
| Event Type | Organ System | Event Term | CRV431 75mg | Placebo, 75mg | CRV431 225mg | Placebo, 225mg |
|---|
Number of adverse events, serious adverse events, and clinical laboratory abnormalities.
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.
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.
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.
