Phase 2
N=263
Emricasan, an Oral Caspase Inhibitor, in Subjects With NASH Cirrhosis and Severe Portal Hypertension
Cirrhosis · Portal Hypertension · Non-alcoholic Steatohepatitis
Bottom Line
View on ClinicalTrials.gov: NCT02960204 ↗Enrolled (actual)
263
Serious AEs
28.5%
Results posted
Jan 2022
Primary outcome: Primary: Mean Change in Hepatic Venous Pressure Gradient (HVPG) — -0.48; -0.81; -0.70; -0.18 mmHg
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Emricasan (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Histogen
- Primary completion
- Oct 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Change in Hepatic Venous Pressure Gradient (HVPG) |
-0.48; -0.81; -0.70; -0.18 | — |
| SECONDARY Improvement of HVPG Response Using a 20% Reduction From Baseline |
8; 14; 10; 9; 53; 48 | — |
| SECONDARY Caspase 3/7 |
-0.01; -0.40; -0.46; -0.04; 0.13; -0.18 | — |
| SECONDARY Alanine Aminotransferase (ALT) |
-7.83; -8.06; -7.06; -1.69; -6.54; -4.16 | — |
Summary
This is a multicenter, randomized, double-blind, placebo-controlled trial involving subjects with NASH cirrhosis and severe portal hypertension (defined as HVPG ≥12 mmHg as determined by the central reader assigned to this study). Upon successful screening, subjects will be randomized to receive either emricasan 50 mg BID, 25 mg BID, or 5 mg BID or matching placebo BID.
Eligibility Criteria
Inclusion Criteria
- Male or female subjects 18 years or older, able to provide written informed consent and able to understand and willing to comply with the requirements of the study.
- Cirrhosis due to NASH with exclusion of other causes of cirrhosis (e.g. chronic viral hepatitis, alcoholic liver disease, etc.)
- Compensated cirrhosis OR Decompensated cirrhosis with no more than 1 prior significant decompensating event
- Severe portal hypertension defined as HVPG ≥12 mmHg
- Subjects who are on NSBB, nitrates, diuretics, lactulose, rifaximin, or statins must be on a stable dose for at least 3 months prior to Day 1
- Willingness to utilize effective contraception (for both males and females of childbearing potential) from Screening to 4 weeks after the last dose of study drug
Exclusion Criteria
- Evidence of severe decompensation
- Severe hepatic impairment defined as a Child-Pugh score ≥10
- ALT (alanine transaminase) > 3 times upper limit of normal (ULN) or AST (aspartate transaminase) >5 times ULN during screening
- Estimated creatinine clearance 50 ng/mL
- History or presence of clinically concerning cardiac arrhythmias, or prolongation of screening (pre-treatment) QTcF interval of >500 msec
- History of or active malignancies, other than those successfully treated with curative intent and believed to be cured
- Prior liver transplant
- Change in diabetes medications or vitamin E within 3 months of screening
- Uncontrolled diabetes mellitus (HbA1c >9%) within 3 months of screening
- Significant systemic or major illness other than liver disease
- HIV infection
- Use of controlled substances (including inhaled or injected drugs) or non-prescribed use of prescription drugs within 1 year of screening
- If female: planned or known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding
- Previous treatment with emricasan or active investigational medication (except methacetin) in a clinical trial within 3 months prior to Day 1
Data sourced from ClinicalTrials.gov (NCT02960204). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.