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

Liver Cirrhosis Clinical Trial

— PH  

Official title:

An Open-Label Pilot Trial to Evaluate the Safety, Tolerability and Efficacy of IDN-6556 in Cirrhotic Subjects With Portal Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02230683
• Other study ID #: IDN-6556-11
• Status: Completed
• Phase: Phase 2
• First received: August 28, 2014
• Last updated: July 28, 2015
• Start date: August 2014
• Est. completion date: June 2015

Study information

• Verified date: May 2015
• Source: Conatus Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

Studies in patients with liver disease have demonstrated that cCK18 is elevated in the serum of patients and has been associated with disease severity. Studies have also shown that cCK18 is generally elevated to a higher degree in cirrhosis than in other liver diseases. In addition, increasing stages of cirrhosis from Child-Pugh A, Child-Pugh B to Child-Pugh C are associated with progressively higher levels of caspase cleaved cytokeratin 18. This suggests that apoptosis and caspase activity are associated with the severity of disease. IDN-6556 and its ability to inhibit inflammation and apoptosis may have a beneficial impact on both the dynamic and structural components associated with the pathogenesis of portal hypertension in cirrhosis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: June 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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:

1. Splenomegaly, on imaging and/or clinical evaluation, with platelet count of <120,000 at study entry, or

2. Presence of small sized varices on screening endoscopy and/or collateral circulation on imaging, or

3. 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.

Exclusion Criteria:

• 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

• Child-Pugh score of 10-15

• Use of concomitant vasoactive drugs (at or within 3 months of Screening) that may impair hepatic blood flow

• Change in dose or regimen within 3 months of Screening of:

1. Fibrates or statins

2. Angiotensin II receptor antagonist or angiotensin converting enzyme (ACE) inhibitor

• Use of the following drugs within 2 months of Screening:

1. Systemic corticosteroids

2. Pentoxifylline

3. Known or suspected use of illicit drugs or drugs of abuse (allowed if medically prescribed or indicated)

• Concomitant pancreatitis

• Evidence of portal vein thrombosis on Doppler ultrasound of the portal vasculature

• Active inflammatory bowel disease

• Diagnosed or suspected systemic lupus erythematosus (SLE) and/or rheumatoid arthritis (RA)

• Autoimmune hepatitis

• Hepatocellular carcinoma (HCC) at entry into the study

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatic Cirrhosis
• Hypertension
• Hypertension, Portal
• Liver Cirrhosis
• Portal Hypertension

Intervention

Drug:
• IDN-6556
25 mg BID

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	St. Luke's Health Baylor College of Medicine	Houston	Texas
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	North Shore University Hospital	Manhasset	New York
United States	University of Miami	Miami	Florida
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Bon Secours Mary Immaculate Hospital	Newport News	Virginia
United States	New York University Lagone Medical Center	NYC	New York
United States	Albert Einstein Medical Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Bon Secours St. Mary's Hospital	Richmond	Virginia
United States	McGuire DVAMC	Richmond	Virginia
United States	University of Utah Hospital	Salt Lake City	Utah
United States	Johns Hopkins Sibley Memorial Hospital	Washington	District of Columbia
United States	VA Connecticut Healthcare System	West Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Conatus Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	cCK18	Change in cCK18 will be assessed	28 days	No
Primary	Hepatic Venous Pressure Gradient (HVPG)	Changes in HVPG from Baseline will be assessed	28 days	No
Secondary	Liver function: ALT/AST	Changes from Baseline will be assessed	28 days	No
Secondary	Serum Biomarkers: flCK 18/M65, Caspase 3/7	Changes from baseline will be assessed	28 days	No
Secondary	MELD	Changes from baseline will be assessed	28 days	No
Secondary	MELD-Na	Changes from baseline will be assessed	28 Days	No
Secondary	Child-Pugh Classification	tabulated by visit	28 Days	No