CirrhosisPhase 2ENCORE-PHNCT02960204

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

A Phase 2 study testing Emricasan in people with Cirrhosis and Portal Hypertension, run by Histogen at 37 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Cirrhosis, Portal Hypertension, Non-alcoholic Steatohepatitis
What is being tested?: Emricasan
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 263 participants
Where: 37 sitesin 3 countries
Study dates: 17 Oct 2016to 8 Apr 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 19Show fewer

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

Trial locations and contacts

37 sites in 3 countries.

Country

City, postcode or hospital

37 sites in 3 countries

United States22 sites

Arlington
Arlington, Texas, 76012
Atlanta
Atlanta, Georgia, 30309
Baltimore
Baltimore, Maryland, 21202
Clive
Clive, Iowa, 50325
Detroit
Detroit, Michigan, 48202
Durham
Durham, North Carolina, 27710
Germantown
Germantown, Tennessee, 38138
Houston
Houston, Texas, 77030
Kansas City
Kansas City, Missouri, 64131
Norfolk
Norfolk, Virginia, 23502
Palmetto Bay
Palmetto Bay, Florida, 33157
Pasadena
Pasadena, California, 91105
Philadelphia
Philadelphia, Pennsylvania, 19104
Philadelphia
Philadelphia, Pennsylvania, 19141
Rialto
Rialto, California, 92377
Richmond
Richmond, Virginia, 23226
Richmond
Richmond, Virginia, 23249
Rochester
Rochester, Minnesota, 55905
Saint Paul
Saint Paul, Minnesota, 55114
San Antonio
San Antonio, Texas, 78215
San Antonio
San Antonio, Texas, 78233
Seattle, Washington
Seattle, Washington, 98104

Other trials in United States

Spain10 sites

Barcelona
Barcelona, 08035
Barcelona
Barcelona, 08036
San Sebastian
Donostia / San Sebastian, 20014
Madrid
Madrid, 28006
Madrid
Madrid, 28034
Madrid
Madrid, 28046
Majadahonda
Majadahonda, 28222
Santander
Santander, 39008
Valencia
Valencia, 46010
Valencia
Valencia, 46104

Other trials in Spain

Germany5 sites

Bonn
Bonn, 53127
Halle (Saale)
Halle, 06120
Leipzig
Leipzig, 04103
Mainz
Mainz, 55131
Münster
Münster, 48149

Other trials in Germany

About this study

Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Emricasan, an Oral Caspase Inhibitor, in Subjects With Non-Alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension

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.

Conditions: Cirrhosis, Portal Hypertension, Non-alcoholic Steatohepatitis
Being tested: Emricasan, Placebo
Keywords: cirrhosis, Portal Hypertension, Non-alcoholic Steatohepatitis, Liver cirrhosis
Medical subject headings: Fibrosis, Hypertension, Portal, Non-alcoholic Fatty Liver Disease, Liver Cirrhosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EmricasanDrug
PlaceboDrug

Study groups in NCT02960204
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (3)

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
Measured: Baseline to Week 24
Caspase 3/7
To assess whether number of Caspase 3/7 biomarkers is affected by emricasan as compared to placebo
Measured: Baseline to Week 24, Baseline to Week 48
Alanine Aminotransferase (ALT)
To assess whether amount of non-specific (ALT) biomarkers are affected by emricasan compared to placebo
Measured: Baseline to Week 24 and Baseline to Week 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Oct 20168 Apr 2019

First posted9 Nov 2016 (estimated)
Study start17 Oct 2016
Primary completion2 Oct 2018
Study completion8 Apr 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for CirrhosisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 263 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02960204
Sponsor's protocol ID: IDN-6556-41
Acronym: ENCORE-PH
Status last verified: Dec 2021
First submitted: 29 Jul 2016
Last updated: 11 Feb 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: There is no plan to share this data with outside researchers

Publications

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.
PubMed 31870950

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 11 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Emricasan, an Oral Caspase Inhibitor, in Subjects With Non-Alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension
ClinicalTrials.gov ID: NCT02960204
Acronym / sponsor ID: ENCORE-PH / IDN-6556-41
Conditions: Cirrhosis, Portal Hypertension, Non-alcoholic Steatohepatitis
Keywords: cirrhosis, Portal Hypertension, Non-alcoholic Steatohepatitis, Liver cirrhosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 263 participants (actual)
Lead sponsor: HistogenIndustry (pharma, biotech, devices)
Study start: 17 Oct 2016 (actual)
Primary completion: 2 Oct 2018 (actual)
Study completion: 8 Apr 2019 (actual)
First posted: 9 Nov 2016 (estimated)
Results: Posted 14 Jan 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Emricasan (5 mg)	Active comparator	Drug: EmricasanSubjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day.
Emricasan (25 mg)	Active comparator	Drug: EmricasanSubjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day.
Emricasan (50 mg)	Active comparator	Drug: EmricasanSubjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day.
Matching Placebo	Placebo comparator	Drug: PlaceboSubjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (19 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Emricasan	Drug	Emricasan (25 mg), Emricasan (5 mg), Emricasan (50 mg)
Placebo	Drug	Matching Placebo

Primary outcome

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

3 secondary outcomes

Improvement of HVPG Response Using a 20% Reduction From Baseline
Time frame: Baseline to Week 24
Caspase 3/7
Time frame: Baseline to Week 24, Baseline to Week 48
Alanine Aminotransferase (ALT)
Time frame: Baseline to Week 24 and Baseline to Week 48

Results and safety

Results posted to the registry on 14 Jan 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Emricasan (5 mg)	65	36
Emricasan (25 mg)	65	44
Emricasan (50 mg)	66	37
Matching Placebo	67	38

Primary outcome: Mean Change in Hepatic Venous Pressure Gradient (HVPG)

Time frame: Baseline to Week 24. Mean (Standard Deviation). Unit: mmHg

Measure	Emricasan (5 mg) n = 61	Emricasan (25 mg) n = 62	Emricasan (50 mg) n = 56	Matching Placebo n = 64
Value	-0.48 (3.356)	-0.81 (3.669)	-0.70 (3.400)	-0.18 (3.028)

Population analysed: Full analysis set (Multiple Imputation)

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Emricasan (5 mg)	15 of 65 (23.1%)	59 of 65 (90.8%)	1 of 65
Emricasan (25 mg)	23 of 65 (35.4%)	62 of 65 (95.4%)	2 of 65
Emricasan (50 mg)	21 of 66 (31.8%)	57 of 66 (86.4%)	1 of 66
Matching Placebo	16 of 67 (23.9%)	61 of 67 (91%)	0 of 67

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 31870950Garcia-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.
Individual participant dataSharing planned: No. There is no plan to share this data with outside researchers

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jeanette M Wetzel study director

Histogen

Samuel Mboggo study director

Histogen

Ruqayyah Abdulrahoof study director

Histogen

37 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Emricasan in people with Cirrhosis and Portal Hypertension, run by Histogen at 37 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in United States, Spain, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change in Hepatic Venous Pressure Gradient (HVPG) (time frame: Baseline to Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02960204, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2022.