A Study of IDN-6556 in Cirrhotic Subjects With Portal Hypertension

NCT02230683 | Completed Phase 2 Results DMC

• 1 other identifier: IDN-6556-11
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 16

Brief Summary

This is an open-label pilot study to evaluate the safety, tolerability, and efficacy of IDN-6556 in treating portal hypertension in subjects with liver cirrhosis.

Conditions

Liver Cirrhosis; Hepatic Cirrhosis; Portal Hypertension

Keywords

Liver Cirrhosis; Hepatic Cirrhosis; Portal Hypertension

Outcome Measures

Primary Outcomes (3)

• Hepatic Venous Pressure Gradient (HVPG)

  Mean change of HVPG \[mmHg\] from Baseline to Day 28/EOT (end of treatment) for IDN-6556

  Baseline to Day 28/EOT (end of treatment)

• cCK18/M30

  Absolute Mean Change of caspase-cleaved cytokeratin serum levels (cCK18/M30); the statistical analysis is based on the mean change in log-transformed cCK18/M30 from Baseline to Day 28/EOT (end of treatment) for IDN-6556

  Change from Baseline to Day 28/EOT

• Change in cCK18/M30

  Median change of caspase-cleaved cytokeratin serum levels (cCK18/M30) from Baseline to Day 28/EOT (end of treatment) for IDN-6556

  Baseline to Day 28/EOT (end of treatment)

Secondary Outcomes (3)

• Change in Alanine Aminotransferase (ALT)

  Baseline to 28 days/EOT

• Change in Aspartate Aminotransferase (AST)

  Baseline to 28 days/EOT

• Concentration of Caspase 3/7 RLU

  Baseline to 28 days/EOT

Study Arms (3)

IDN-6556 - Overall population

EXPERIMENTAL

Overall evaluable population treated with IDN-6556 25 mg twice daily

Drug: IDN-6556

IDN-6556 - Subgroup with Baseline HVPG < 12 mmHg

EXPERIMENTAL

Subgroup for patients with Baseline HVPG \< 12 mmHg that have been treated with IDN-6556 25 mg twice daily

Drug: IDN-6556

IDN-6556 - Subgroup Baseline HVPG ≥ 12 mmHg

EXPERIMENTAL

Subgroup for patients with Baseline HVPG ≥ 12 mmHg that have been treated with IDN-6556 25 mg twice daily

Drug: IDN-6556

Interventions

IDN-6556 DRUG

25 mg BID

Also known as: emricasan, PF-013491390

IDN-6556 - Overall population; IDN-6556 - Subgroup Baseline HVPG ≥ 12 mmHg; IDN-6556 - Subgroup with Baseline HVPG < 12 mmHg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects of minimum adult legal age (according to local laws for signing the informed consent document), able to provide written informed consent, and able to understand and willing to comply with the requirements of the study
• Clinical, radiological, or biochemical evidence of liver cirrhosis
• Evidence of portal hypertension as evidenced by any of the following:
• Splenomegaly, on imaging and/or clinical evaluation, with platelet count of \<120,000 at study entry, or
• Presence of small sized varices on screening endoscopy and/or collateral circulation on imaging, or
• Presence of medium/large varices that have never bled and have been obliterated with endoscopic ligation
• Portal hypertension defined as a hepatic venous pressure gradient (HVPG) \>5 mmHg at Screening
• Willingness to utilize two reliable forms of contraception (for both males and females of childbearing potential) from Screening to one month after the last dose of study drug.

You may not qualify if:

• Decompensated cirrhosis as defined by the presence of overt ascites (requiring diuretics), overt encephalopathy (requiring specific therapy), or history of variceal hemorrhage.
• Known infection with HIV
• Hepatic failure defined as total bilirubin ≥12 mg/dL
• Other non-liver organ failure, including:
• Renal failure defined as creatinine ≥ 2.0 mg/dL
• Cerebral failure defined as hepatic encephalopathy grade III or IV
• Coagulation failure defined as INR ≥ 2.5 or platelets ≤ 20x109/L
• Hemodynamic requirement for inotropic support
• Child-Pugh score of 10-15 (Child-Pugh C classification)
• Use of vasoactive drugs (at or within 3 months of Screening) that may impair hepatic blood flow; examples include but are not limited to:
• β-blockers, including carvedilol
• Nitrates
• Vasopressin (or analogues)
• Phosphodiesterase inhibitors (prescribed daily for pulmonary hypertension; p.r.n. use for erectile dysfunction is permitted)
• Change in dose or regimen within 3 months of Screening of:

Sponsors & Collaborators

• Conatus Pharmaceuticals Inc.: lead

Study Sites (16)

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

Location

Johns Hopkins Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Rutgers New Jersey Medical School

Newark, New Jersey, 07103, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

New York University Lagone Medical Center

New York, New York, 10016, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Albert Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

St. Luke's Health Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

Bon Secours Mary Immaculate Hospital

Newport News, Virginia, 23602, United States

Location

Bon Secours St. Mary's Hospital

Richmond, Virginia, 23226, United States

Location

McGuire DVAMC

Richmond, Virginia, 23249, United States

Location

MeSH Terms

Conditions

Liver Cirrhosis; Hypertension, Portal

Interventions

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

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Jean L. Chan, MD
• Organization: Conatus Pharmaceuticals Inc.

jchan@conatuspharma.com

(858) 376-2632

Study Officials

• David Hagerty, MD

  Conatus Pharmaceuticals Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2014
• First Posted: September 3, 2014
• Study Start: August 1, 2014
• Primary Completion: May 1, 2015
• Study Completion: June 1, 2015
• Last Updated: December 21, 2016
• Results First Posted: December 21, 2016

Record last verified: 2016-10

Locations

US (16)