Emricasan, an Oral Caspase Inhibitor, in Subjects With NA... | NCT02960204

Label	Type	Description	Intervention Names
Emricasan (5 mg)	Active Comparator	Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day.	Drug: Emricasan
Emricasan (25 mg)	Active Comparator	Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day.	Drug: Emricasan
Emricasan (50 mg)	Active Comparator	Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day.	Drug: Emricasan
Matching Placebo	Placebo Comparator	Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Emricasan	Drug		Emricasan (25 mg) Emricasan (5 mg) Emricasan (50 mg)
Placebo

Measure	Description	Time Frame
Mean Change in Hepatic Venous Pressure Gradient (HVPG)	To assess the mean change from baseline to Week 24 in hepatic venous pressure gradient (HVPG)	Baseline to Week 24

Measure	Description	Time Frame
Improvement of HVPG Response Using a 20% Reduction From Baseline	To assess subjects who have at least a 20 percent reduction from baseline in HVPG	Baseline to Week 24
Caspase 3/7	To assess whether number of Caspase 3/7 biomarkers is affected by emricasan as compared to placebo

Eligibility Module

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 <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

Name	Affiliation	Role
Jeanette M Wetzel	Histogen	Study Director
Samuel Mboggo	Histogen	Study Director
Ruqayyah Abdulrahoof	Histogen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pasadena		Pasadena	California	91105	United States
Rialto

PubMed Identifier	Type	Citation	Retractions
31870950	Result	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.

ID	Title	Description
FG000	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. Emricasan
FG001	Emricasan (25 mg)

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 14, 2018	Nov 22, 2019

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00065 ParticipantsBG00165 ParticipantsBG00266 ParticipantsBG003

Age, Continuous

Mean

Standard Deviation

years

Title	Denominators	Categories
	ParticipantsBG00065 ParticipantsBG00165 ParticipantsBG002

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00065 ParticipantsBG00165 ParticipantsBG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00065 ParticipantsBG00165 ParticipantsBG002

Race (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00065 ParticipantsBG00165 ParticipantsBG002

Region of Enrollment

Number

participants

Title	Denominators	Categories
United States	ParticipantsBG00065 ParticipantsBG00165 ParticipantsBG002

Hepatic Venous Pressure Gradient

Mean

Standard Deviation

mmHg

Title	Denominators	Categories
	ParticipantsBG00065 ParticipantsBG00165 ParticipantsBG002

Taking Non-Selective Beta Blockers at Baseline

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00065 ParticipantsBG00165 ParticipantsBG002

Cirrhosis Baseline Status

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00065 ParticipantsBG00165 ParticipantsBG002

Varices

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00065 ParticipantsBG00165 ParticipantsBG002

Compensated Status with Varices

Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00065 ParticipantsBG00164 ParticipantsBG002

Model for End-Stage Liver Disease (MELD) Score

Scores range from 6.0 to 40.0, and higher MELD scores indicate more severe disease.

Mean

Standard Deviation

units on a scale

Title	Denominators	Categories
	ParticipantsBG00065 ParticipantsBG00165 ParticipantsBG002

MELD Classification (Median Cut)

Scores range from 6.0 to 40.0, and higher MELD scores indicate more severe disease.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00065 ParticipantsBG00165 ParticipantsBG002

MELD Component: Total Bilirubin

Mean

Standard Deviation

mg/dL

Title	Denominators	Categories
	ParticipantsBG00065 ParticipantsBG00165 ParticipantsBG002

MELD Component: Serum Creatine

Mean

Standard Deviation

mg/dL

Title	Denominators	Categories
	ParticipantsBG00065 ParticipantsBG00165 ParticipantsBG002

MELD Component: International Normalized Ratio

Patients are assigned a score from 6 to 40. Worst score of 6 equates to 90% 3-month survival rate, while a best score of 40 equates to 7% 3-month survival rate.

Mean

Standard Deviation

mg/dL

Title	Denominators	Categories
	ParticipantsBG00065 ParticipantsBG00165 ParticipantsBG002

Child-Pugh Score

Scores range from 5 to 15, and higher Child-Pugh scores indicate more severe disease.

Mean

Standard Deviation

units on a scale

Title	Denominators	Categories
	ParticipantsBG00065 ParticipantsBG00165 ParticipantsBG002

Child-Pugh Classification

Scores range from 5 to 15, and higher Child-Pugh scores indicate more severe disease. A = scores from 5 to 6; B = scores from 7 to 9; C = scores from 10 to 15.

Two subjects (one in the 5 mg emricasan arm and one in the 25 mg emricasan arm) did not have data available.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00064 ParticipantsBG00164 ParticipantsBG002

Child-Pugh Component: Total Bilirubin