Study of CTS-1027 in Hepatitis C Patients

Chronic Hepatitis C Virus Infection Clinical Trial

Official title:

A Dose Response Study of CTS-1027 in Hepatitis C Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00570336
• Other study ID #: CTS-1027-01
• Status: Completed
• Phase: Phase 2
• First received: December 6, 2007
• Last updated: September 14, 2010
• Start date: December 2007
• Est. completion date: July 2009

Study information

• Verified date: September 2010
• 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 purpose of this study is to determine if CTS-1027 can lower elevated liver enzymes in patients with chronic HCV infection.

Description:

Randomized, placebo-controlled, double-blind, parallel group, multicenter, dose response trial utilizing four doses of CTS-1027, administered orally once daily, in outpatients with chronic hepatitis C virus (HCV) infection.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 87
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• 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 HCV infection

• Unsuccessful HCV treatment defined as one or more of the following criteria:

1. Failure to achieve a virologic response during previous therapy, or

2. Failure to tolerate therapy, or

3. Failure to maintain a sustained virologic response, or

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

• Liver impairment, as defined by either aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels 1.5 - 7 x ULN on at least two occasions, seven or more days apart, during the baseline period

• Alpha-fetoprotein (AFP) <= 50 ng/mL

• Hemoglobin >= 10 g/dL, platelet count >= 75 x 109/L, and white blood cell count >= 1.5 x 109/L

• Willingness to utilize adequate contraception (if female, evidenced by being postmenopausal for at least 6 months or using contraceptive pill; for both females and males, being surgically sterile, or using two forms of barrier contraception) from screening to at least one month after the completion of the trial.

Exclusion Criteria:

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

1. Prior liver biopsy showing cirrhosis

2. Prior liver biopsy showing bridging fibrosis (Metavir >2 or Ishak >3) more than 2 years ago in the absence of newer liver biopsy results

3. Prothrombin time: 3 seconds > control

4. Total bilirubin >= 1.5 x Upper limit of the normal range (ULN), or > 3 x ULN for unconjugated bilirubin

5. Serum albumin below normal limits

6. AST or ALT > 7 x ULN during baseline period

7. Evidence of portal hypertension including:

• Splenomegaly or evidence of portal hypertension (i.e., enlarged portal vein and varices) on ultrasound,

• Varices in esophagogastroduodenoscopy (EGD); or

• Ascites

• 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 or urine pregnancy test

• Last baseline AST and ALT level prior to Day 1 of < 1.5 x ULN

• Renal impairment (creatinine > 1.5 x ULN) or hepatorenal syndrome

• Pancreatitis

• Hospitalization for liver disease within 60 days of screening

• Use of concomitant or prior drug therapy for HCV at screening, including the use of:

1. drugs with presumed anti-HCV activity in the prior three months

2. corticosteroids in the past 30 days

3. potentially hepatotoxic drugs in the past 30 days (including alpha methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin)

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

• History of alcohol abuse 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 Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C Virus Infection
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Virus Diseases

Intervention

Drug:
• CTS-1027
Eligible patients were randomized to one of four doses of CTS-1027 (2.5 mg, 5 mg, 10 mg, or 30 mg) or placebo qd (quaque die, once daily).

Other:
• Placebo
Eligible patients were randomized to one of four doses of CTS-1027 (2.5 mg, 5 mg, 10 mg, or 30 mg) or placebo qd.

Locations

Country	Name	City	State
United States	Digestive Healthcare of Georgia	Atlanta	Georgia
United States	University of Colorado Denver	Aurora	Colorado
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Bronx VA Medical Center	Bronx	New York
United States	Consultants of Clinical Research	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Advanced Liver Therapies - Baylor College of Medicine	Houston	Texas
United States	VAMC - Baylor College of Medicine	Houston	Texas
United States	Scripps Clinic	La Jolla	California
United States	University of Miami	Miami	Florida
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Mt. Sinai School of Medicine	New York	New York
United States	McGuire Hospital DVAMC	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Kaiser Permanente	San Diego	California
United States	California Pacific Medical Center	San Francisco	California
United States	Henry Ford Health System	West Bloomfield	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Conatus Pharmaceuticals Inc.	FGK Clinical Research GmbH

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of adverse events at each dose level		4 to 24 weeks	Yes
Primary	Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) levels at each dose		4-24 Weeks	Yes
Secondary	Peak and trough levels of CTS-1027 in plasma		4 to 24 weeks	Yes