Clinical trial NCT04480710: A Study of CRV431 Dosed Once Daily in NASH Induced F2 and F3 Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: NASH - Nonalcoholic Steatohepatitis
Fibrosis, Liver
NAFLD - Nonalcoholic Fatty Liver Disease
Keywords: Anti-fibrotic
Lead sponsor: Hepion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-07-21
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, multi-center, single-blind
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Number of Safety and Tolerability Events of CRV431 Versus Placebo.
timeFrame: Time from informed consent to study day 42.
measure: Tmax, of Once Daily (QD) 75mg and 225mg mg Doses of CRV431 is Presumed Non-alcoholic Steatohepatitis F2/F3 Fibrosis Subjects.
timeFrame: Day 1 and Day 28
measure: Cmax, of Once Daily (QD) 75mg and 22mg mg Doses of CRV431 is Presumed Non-alcoholic Steatohepatitis F2/F3 Fibrosis Subjects.
timeFrame: Day 1 and Day 28
measure: AUC 0-last, of Once Daily (QD) 75mg and 225mg mg Doses of CRV431 in Presumed Non-alcoholic Steatohepatitis F2/F3 Fibrosis Subjects.
timeFrame: Timepoints for data collection include 0, 2.0 hours, 4.0 hours, 8 hours on both Day 1 and Day 28.
Secondary outcomes:
Other outcomes:
Locations:
city: Orange
country: United States
facility: Conquest Clinical Research
state: California
city: Poway
country: United States
facility: Alliance Clinical Research
state: California
city: Miami
country: United States
facility: La Salud Research, Inc.
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Sarasota
country: United States
facility: Covenant Research, LLC.
state: Florida
city: Marietta
country: United States
facility: Gastrointestinal Specialists of Georgia
state: Georgia
city: Columbus
country: United States
facility: Aventiv Research Inc.
state: Ohio
city: San Antonio
country: United States
facility: Quality Research Inc.
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Research Group
state: Texas
city: San Juan
country: Puerto Rico
facility: FDI Clinical Research
Study officials:
affiliation: Hepion Pharmaceuticals, Inc.
name: Carlos Canizares, R.Ph.
role: STUDY_DIRECTOR
References: