NCT02960204

Brief 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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
263

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Oct 2016

Geographic Reach
3 countries

37 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 29, 2016

Completed
3 months until next milestone

Study Start

First participant enrolled

October 17, 2016

Completed
23 days until next milestone

First Posted

Study publicly available on registry

November 9, 2016

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 2, 2018

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 8, 2019

Completed
2.8 years until next milestone

Results Posted

Study results publicly available

January 14, 2022

Completed
Last Updated

February 11, 2022

Status Verified

December 1, 2021

Enrollment Period

2 years

First QC Date

July 29, 2016

Results QC Date

June 18, 2021

Last Update Submit

January 13, 2022

Conditions

CirrhosisPortal HypertensionNon-alcoholic Steatohepatitis

Keywords

cirrhosisPortal HypertensionNon-alcoholic SteatohepatitisLiver cirrhosis

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (3)

  • Improvement of HVPG Response Using a 20% Reduction From Baseline

    Baseline to Week 24

  • Caspase 3/7

    Baseline to Week 24, Baseline to Week 48

  • Alanine Aminotransferase (ALT)

    Baseline to Week 24 and Baseline to Week 48

Study Arms (4)

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

Interventions

EmricasanDRUG
Emricasan (25 mg)Emricasan (5 mg)Emricasan (50 mg)
PlaceboDRUG
Matching Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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

You may not qualify if:

  • 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
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (37)

Pasadena

Pasadena, California, 91105, United States

Location

Rialto

Rialto, California, 92377, United States

Location

Palmetto Bay

Palmetto Bay, Florida, 33157, United States

Location

Atlanta

Atlanta, Georgia, 30309, United States

Location

Clive

Clive, Iowa, 50325, United States

Location

Baltimore

Baltimore, Maryland, 21202, United States

Location

Detroit

Detroit, Michigan, 48202, United States

Location

Rochester

Rochester, Minnesota, 55905, United States

Location

Saint Paul

Saint Paul, Minnesota, 55114, United States

Location

Kansas City

Kansas City, Missouri, 64131, United States

Location

Durham

Durham, North Carolina, 27710, United States

Location

Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Philadelphia

Philadelphia, Pennsylvania, 19141, United States

Location

Germantown

Germantown, Tennessee, 38138, United States

Location

Arlington

Arlington, Texas, 76012, United States

Location

Houston

Houston, Texas, 77030, United States

Location

San Antonio

San Antonio, Texas, 78215, United States

Location

San Antonio

San Antonio, Texas, 78233, United States

Location

Norfolk

Norfolk, Virginia, 23502, United States

Location

Richmond

Richmond, Virginia, 23226, United States

Location

Richmond

Richmond, Virginia, 23249, United States

Location

Seattle, Washington

Seattle, Washington, 98104, United States

Location

Bonn

Bonn, 53127, Germany

Location

Halle (Saale)

Halle, 06120, Germany

Location

Leipzig

Leipzig, 04103, Germany

Location

Mainz

Mainz, 55131, Germany

Location

Münster

Münster, 48149, Germany

Location

Barcelona

Barcelona, 08035, Spain

Location

Barcelona

Barcelona, 08036, Spain

Location

San Sebastian

Donostia / San Sebastian, 20014, Spain

Location

Madrid

Madrid, 28006, Spain

Location

Madrid

Madrid, 28034, Spain

Location

Madrid

Madrid, 28046, Spain

Location

Majadahonda

Majadahonda, 28222, Spain

Location

Santander

Santander, 39008, Spain

Location

Valencia

Valencia, 46010, Spain

Location

Valencia

Valencia, 46104, Spain

Location

Related Publications (1)

  • 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.

    PMID: 31870950RESULT

MeSH Terms

Conditions

FibrosisHypertension, PortalNon-alcoholic Fatty Liver DiseaseLiver Cirrhosis

Interventions

3-(2-(2-tert-butylphenylaminooxalyl)aminopropionylamino)-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and SymptomsLiver DiseasesDigestive System DiseasesFatty Liver

Results Point of Contact

Title
Mark Hubka, Executive Director, Medical Affairs
Organization
Histogen Inc.
mhubka@histogen.com
858-526-3109

Study Officials

  • Jeanette M Wetzel

    Histogen

    STUDY DIRECTOR

  • Samuel Mboggo

    Histogen

    STUDY DIRECTOR

  • Ruqayyah Abdulrahoof

    Histogen

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 29, 2016

First Posted

November 9, 2016

Study Start

October 17, 2016

Primary Completion

October 2, 2018

Study Completion

April 8, 2019

Last Updated

February 11, 2022

Results First Posted

January 14, 2022

Record last verified: 2021-12

Data Sharing

IPD Sharing
Will not share

There is no plan to share this data with outside researchers

Locations

ES(10)DE(5)US(22)