CTS-1027 in Interferon-Naive Hepatitis C Patients

Hepatitis C Clinical Trial

Official title:

A Trial of CTS-1027 in Interferon-Naive Hepatitis C Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00925990
• Other study ID #: CTS-1027-03
• Status: Completed
• Phase: Phase 2
• First received: June 19, 2009
• Last updated: February 27, 2012
• Start date: June 2009
• Est. completion date: July 2010

Study information

• Verified date: February 2012
• 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

The study is intended to determine whether CTS-1027 either alone or in combination with ribavirin is safe and effective in Hepatitis C patients who have not previously been treated with interferon.

Description:

There are approximately 1 million Hepatitis C (HCV) patients in the US who have failed to respond to, or cannot tolerate, interferon or interferon plus ribavirin therapy. Significant adverse effects of interferon therapy include bone marrow depression (with reduced white blood cell and platelet counts) and major psychiatric disorders (especially depression). Ribavirin is associated with hemolytic anemia in a minority of patients who are treated with it. Patients with chronic HCV infection have a very low incidence of spontaneous viral clearance, have progressive disease, and have a continuing medical need for more efficacious and safer therapy. There is a significant unmet medical need for therapy in HCV patients who cannot (or will not) tolerate interferon-based treatment.

This trial will evaluate the effects of CTS-1027 with or without ribavirin in patients who are previously untreated with interferon including patients with major psychiatric disorders, uncontrolled autoimmune disease, and patients who simply decline treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: July 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female patients of minimum adult legal age (according to local laws for signing the informed consent document), able to provide written informed consent, and understand and comply with the requirements of the trial

• A history of chronic (> 6 months duration) genotype 1 Hepatitis C (HCV) infection

• Unsuitable for interferon-based HCV treatment, defined as at least one of the following three criteria:

• Contra-indicated for interferon treatment due to current or prior psychiatric disorders

• Patient's decision to not pursue interferon-based therapy

• In the opinion of the Principal Investigator, the patient is not a suitable candidate for interferon-based therapy

• a-fetoprotein (AFP) <= 50 ng/mL

• Hemoglobin = 12 g/dL, platelet count = 100 x 109/L, and white blood cell count = 1.5 x 109/L

• Willingness to utilize two reliable forms of contraception (for both males and females of childbearing potential) from screening to at least six months after the completion of the trial.

Exclusion Criteria:

• Decompensated or severe liver disease defined by one or more of the following criteria:

• Prothrombin time 3 seconds > control

• Direct bilirubin = 1.5 x upper limit of normal range (ULN)

• Serum albumin below normal limits

• AST or ALT > 7 x ULN at screening

• Evidence of portal hypertension including:

1. Varices on esophagogastroduodenoscopy (EGD) with or without a history of gastrointestinal bleeding; or

2. Ascites

• Cirrhosis defined by one or both of the following criteria:

• Liver biopsy showing cirrhosis

• Other clinical signs and symptoms suggestive of cirrhosis

• Prior therapy for HCV with an interferon-based regimen

• Hepatocellular carcinoma (HCC) or suspicion of HCC clinically or on ultrasound (or other imaging techniques)

• Known history or presence of human immunodeficiency virus (HIV) infection

• Co-infection with hepatitis B virus (HBV)

• If female: pregnant, lactating, or positive serum pregnancy test

• Renal impairment (creatinine > 1.5 x ULN), creatinine clearance < 50 mL/min, or hepatorenal syndrome

• Hospitalization for liver disease within 60 days of screening

• Use of concomitant or prior drug therapy for HCV three months prior to screening

• Use of drugs of abuse in the prior three months (allowed if medically prescribed or indicated)

• History of alcohol abuse (> 50 g per day) within the past year

• History or presence of clinically concerning cardiac arrhythmias or prolongation of pre-dose QT or QTc interval of > 450 milliseconds

• Other concomitant disease or condition likely to significantly decrease life expectancy (e.g., moderate to severe congestive heart failure) or any malignancy other than curatively treated skin cancer (basal cell or squamous cell carcinomas), unless adequately treated or in complete remission for ten or more years

• Any patient who has received any investigational drug or device within 30 days of dosing, or who is scheduled to receive another investigational drug or device during the course of this trial.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

Drug:
• ribavirin
200 mg capsules, either 1000 or 1200 mg taken twice daily for up to 24 weeks
• CTS-1027
5 and 10 mg tablets, 15 mg taken twice daily, for up to 24 weeks
• Placebo for ribavirin
Capsules identical to ribavirin in appearance containing inactive ingredients

Locations

Country	Name	City	State
Puerto Rico	Fundacion de Investigacion de Diego	Santurce
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of NC at Chapel Hill	Chapel Hill	North Carolina
United States	Consultants of Clinical Research, Ohio GI and Liver Institute	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Colorado Health Science Center	Denver	Colorado
United States	Duke University Health System	Durham	North Carolina
United States	University of Florida	Gainsville	Florida
United States	VA Medical Center, Houston	Houston	Texas
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Mount Sinai School of Medicine	New York City	New York
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	MN Clinical Research Center	Plymouth	Minnesota
United States	VCU-Medical College of Virginia	Richmond	Virginia
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Kaiser Permanante	San Diego	California
United States	Medical Associates Research Group	San Diego	California
United States	VA Medical Center, San Diego	San Diego	California
United States	St. Louis University	St. Louis	Missouri
United States	Washington Hospital Center	Washington	District of Columbia
United States	University of MA Mem Med Ctr	Worchester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Conatus Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change in HCV-RNA (Hepatitis C Virus Ribonucleic Acid) Levels From Baseline Through 24 Weeks of Treatment	Measure the mean absolute changes in HCV-RNA (Hepatitis C virus ribonucleic acid, also known as "viral load") levels in the blood from before treatment (baseline) through 24 weeks of treatment.; Mean Absolute Change in HCV-RNA (log) = log10(HCV-RNA Week 24) - log10(HCV-RNA Baseline)	Baseline and 24 weeks	Yes
Secondary	Mean Change in Aminotransferases From Baseline to 24 Weeks of Treatment	Mean absolute changes in ALT (alanine aminotransferase)in the blood from before treatment (baseline)through 24 weeks of treatment are presented.; Mean absolute change in ALT (IU/ml)= ALT(Week 24) - ALT(baseline)	Baseline and 24 weeks	Yes