Emricasan, an Oral Caspase Inhibitor, in Subjects With NASH Cirrhosis and Severe Portal Hypertension

NCT ID: NCT02960204

Last Updated: 2022-02-11

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

263 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-10-17

Study Completion Date

2019-04-08

Brief Summary

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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.

Detailed Description

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Conditions

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Cirrhosis Portal Hypertension Non-alcoholic Steatohepatitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Emricasan (5 mg)

Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day.

Group Type ACTIVE_COMPARATOR

Emricasan

Intervention Type DRUG

Emricasan (25 mg)

Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day.

Group Type ACTIVE_COMPARATOR

Emricasan

Intervention Type DRUG

Emricasan (50 mg)

Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day.

Group Type ACTIVE_COMPARATOR

Emricasan

Intervention Type DRUG

Matching Placebo

Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Interventions

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Emricasan

Intervention Type DRUG

Placebo

Intervention Type DRUG

Eligibility Criteria

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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 \<30 mL/min
* Prior transjugular intrahepatic portosystemic shunt or other porto-systemic bypass procedure
* Known portal vein thrombosis
* Symptoms of biliary colic, e.g. due to symptomatic gallstones, within the last 6 months, unless resolved following cholecystectomy
* Current use of medications that are considered inhibitors of OATP1B1 and OATP1B3 transporters
* Alpha-fetoprotein \>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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Histogen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jeanette M Wetzel

Role: STUDY_DIRECTOR

Histogen

Samuel Mboggo

Role: STUDY_DIRECTOR

Histogen

Ruqayyah Abdulrahoof

Role: STUDY_DIRECTOR

Histogen

Locations

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Pasadena

Pasadena, California, United States

Site Status

Rialto

Rialto, California, United States

Site Status

Palmetto Bay

Palmetto Bay, Florida, United States

Site Status

Atlanta

Atlanta, Georgia, United States

Site Status

Clive

Clive, Iowa, United States

Site Status

Baltimore

Baltimore, Maryland, United States

Site Status

Detroit

Detroit, Michigan, United States

Site Status

Rochester

Rochester, Minnesota, United States

Site Status

Saint Paul

Saint Paul, Minnesota, United States

Site Status

Kansas City

Kansas City, Missouri, United States

Site Status

Durham

Durham, North Carolina, United States

Site Status

Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Germantown

Germantown, Tennessee, United States

Site Status

Arlington

Arlington, Texas, United States

Site Status

Houston

Houston, Texas, United States

Site Status

San Antonio

San Antonio, Texas, United States

Site Status

San Antonio

San Antonio, Texas, United States

Site Status

Norfolk

Norfolk, Virginia, United States

Site Status

Richmond

Richmond, Virginia, United States

Site Status

Richmond

Richmond, Virginia, United States

Site Status

Seattle, Washington

Seattle, Washington, United States

Site Status

Bonn

Bonn, , Germany

Site Status

Halle (Saale)

Halle, , Germany

Site Status

Leipzig

Leipzig, , Germany

Site Status

Mainz

Mainz, , Germany

Site Status

Münster

Münster, , Germany

Site Status

Barcelona

Barcelona, , Spain

Site Status

Barcelona

Barcelona, , Spain

Site Status

San Sebastian

Donostia / San Sebastian, , Spain

Site Status

Madrid

Madrid, , Spain

Site Status

Madrid

Madrid, , Spain

Site Status

Madrid

Madrid, , Spain

Site Status

Majadahonda

Majadahonda, , Spain

Site Status

Santander

Santander, , Spain

Site Status

Valencia

Valencia, , Spain

Site Status

Valencia

Valencia, , Spain

Site Status

Countries

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United States Germany Spain

References

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Garcia-Tsao G, Bosch J, Kayali Z, Harrison SA, Abdelmalek MF, Lawitz E, Satapathy SK, Ghabril M, Shiffman ML, Younes ZH, Thuluvath PJ, Berzigotti A, Albillos A, Robinson JM, Hagerty DT, Chan JL, Sanyal AJ; IDN-6556-14 Investigators(double dagger). Randomized placebo-controlled trial of emricasan for non-alcoholic steatohepatitis-related cirrhosis with severe portal hypertension. J Hepatol. 2020 May;72(5):885-895. doi: 10.1016/j.jhep.2019.12.010. Epub 2019 Dec 21.

Reference Type RESULT
PMID: 31870950 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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IDN-6556-41

Identifier Type: -

Identifier Source: org_study_id

NCT04806750

Identifier Type: -

Identifier Source: nct_alias

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