A Study of CRV431 Dosed Once Daily in NASH Induced F2 and F3 Subjects (AMBITION)
Primary Purpose
NASH - Nonalcoholic Steatohepatitis, Fibrosis, Liver, NAFLD - Nonalcoholic Fatty Liver Disease
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
CRV431 75mg
Placebo (1 softgel)
CRV431 225mg
Placebo (3 softgels)
Sponsored by
About this trial
This is an interventional treatment trial for NASH - Nonalcoholic Steatohepatitis focused on measuring Anti-fibrotic
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.
Sites / Locations
- Conquest Clinical Research
- Alliance Clinical Research
- La Salud Research, Inc.
- Progressive Medical Research
- Covenant Research, LLC.
- Gastrointestinal Specialists of Georgia
- Aventiv Research Inc.
- Quality Research Inc.
- Pinnacle Research Group
- FDI Clinical Research
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
CRV431 75mg
Placebo, 75mg
CRV431 225mg
Placebo, 225mg
Arm Description
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
Outcomes
Primary Outcome Measures
Number of Safety and Tolerability Events of CRV431 Versus Placebo.
Number of adverse events, serious adverse events, and clinical laboratory abnormalities.
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.
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.
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT04480710
First Posted
July 9, 2020
Last Updated
July 13, 2022
Sponsor
Hepion Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04480710
Brief Title
A Study of CRV431 Dosed Once Daily in NASH Induced F2 and F3 Subjects
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
June 23, 2020 (Actual)
Primary Completion Date
June 29, 2021 (Actual)
Study Completion Date
October 30, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hepion Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NASH - Nonalcoholic Steatohepatitis, Fibrosis, Liver, NAFLD - Nonalcoholic Fatty Liver Disease
Keywords
Anti-fibrotic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized, multi-center, single-blind
Masking
Participant
Masking Description
placebo-controlled
Allocation
Randomized
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CRV431 75mg
Arm Type
Experimental
Arm Description
CRV431, softgel capsule, 75mg, QD, 28 days, fasted conditions
Arm Title
Placebo, 75mg
Arm Type
Placebo Comparator
Arm Description
Placebo, softgel capsule, QD, 28 days, fasted conditions
Arm Title
CRV431 225mg
Arm Type
Experimental
Arm Description
CRV431, softgel capsule, 225mg, QD, 28 days, fasted conditions
Arm Title
Placebo, 225mg
Arm Type
Placebo Comparator
Arm Description
CRV431, 3 softgel capsules, 225mg, QD, 28 days, fasted conditions
Intervention Type
Drug
Intervention Name(s)
CRV431 75mg
Intervention Description
1 x 75mg softgel capsule
Intervention Type
Drug
Intervention Name(s)
Placebo (1 softgel)
Intervention Description
1 x placebo softgel capsule
Intervention Type
Drug
Intervention Name(s)
CRV431 225mg
Intervention Description
3 x 75mg softgel capsule
Intervention Type
Drug
Intervention Name(s)
Placebo (3 softgels)
Intervention Description
3 x placebo softgel capsule
Primary Outcome Measure Information:
Title
Number of Safety and Tolerability Events of CRV431 Versus Placebo.
Description
Number of adverse events, serious adverse events, and clinical laboratory abnormalities.
Time Frame
Time from informed consent to study day 42.
Title
Tmax, of Once Daily (QD) 75mg and 225mg mg Doses of CRV431 is Presumed Non-alcoholic Steatohepatitis F2/F3 Fibrosis Subjects.
Description
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.
Time Frame
Day 1 and Day 28
Title
Cmax, of Once Daily (QD) 75mg and 22mg mg Doses of CRV431 is Presumed Non-alcoholic Steatohepatitis F2/F3 Fibrosis Subjects.
Description
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.
Time Frame
Day 1 and Day 28
Title
AUC 0-last, of Once Daily (QD) 75mg and 225mg mg Doses of CRV431 in Presumed Non-alcoholic Steatohepatitis F2/F3 Fibrosis Subjects.
Description
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.
Time Frame
Timepoints for data collection include 0, 2.0 hours, 4.0 hours, 8 hours on both Day 1 and Day 28.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carlos Canizares, R.Ph.
Organizational Affiliation
Hepion Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Conquest Clinical Research
City
Orange
State/Province
California
ZIP/Postal Code
92866
Country
United States
Facility Name
Alliance Clinical Research
City
Poway
State/Province
California
ZIP/Postal Code
92064
Country
United States
Facility Name
La Salud Research, Inc.
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
Progressive Medical Research
City
Port Orange
State/Province
Florida
ZIP/Postal Code
32127
Country
United States
Facility Name
Covenant Research, LLC.
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34249
Country
United States
Facility Name
Gastrointestinal Specialists of Georgia
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
Facility Name
Aventiv Research Inc.
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43213
Country
United States
Facility Name
Quality Research Inc.
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78209
Country
United States
Facility Name
Pinnacle Research Group
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
FDI Clinical Research
City
San Juan
ZIP/Postal Code
00927
Country
Puerto Rico
12. IPD Sharing Statement
Plan to Share IPD
No
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A Study of CRV431 Dosed Once Daily in NASH Induced F2 and F3 Subjects
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