Study of CTS-1027 in Hepatitis C Patients

Phase 2

Completed

• Conditions: Chronic Hepatitis C Virus Infection
• Interventions: Drug: CTS-1027; Other: Placebo

• Registration Number: NCT00570336
• Lead Sponsor: Conatus Pharmaceuticals Inc.

Brief Summary

The purpose of this study is to determine if CTS-1027 can lower elevated liver enzymes in patients with chronic HCV infection.

Detailed 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.

Study Timeline

• Study Start: 2007-12
• Study First Submitted: 2007-12-06
• Study First Submitted QC: 2007-12-06
• Study First Posted: 2007-12-10
• Primary Completion: 2009-07
• Study Completion: 2009-07
• Disposition First Submitted: 2010-08-31
• Status Verified: 2010-09
• Disposition First Submitted QC: 2010-09-09
• Disposition First Posted: 2010-09-13
• Last Update Submitted: 2010-09-14
• Last Update Posted: 2010-09-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 87

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
10 mg CTS-1027	CTS-1027	10 mg CTS-1027
30 mg CTS-1027	CTS-1027	30 mg CTS-1027
Placebo	Placebo	Placebo
2.5 milligram (mg) CTS-1027	CTS-1027	2.5 mg CTS-1027
5 mg CTS-1027	CTS-1027	5 mg CTS-1027

Primary Outcome Measures

Name	Time	Method
Number of adverse events at each dose level	4 to 24 weeks
Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) levels at each dose	4-24 Weeks

Secondary Outcome Measures

Name	Time	Method
Peak and trough levels of CTS-1027 in plasma	4 to 24 weeks

Trial Locations

Locations (19)

Kaiser Permanente; 🇺🇸 San Diego, California, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of Colorado Denver; 🇺🇸 Aurora, Colorado, United States

Scripps Clinic; 🇺🇸 La Jolla, California, United States

University of Miami; 🇺🇸 Miami, Florida, United States

California Pacific Medical Center; 🇺🇸 San Francisco, California, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Henry Ford Health System; 🇺🇸 West Bloomfield, Michigan, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Consultants of Clinical Research; 🇺🇸 Cincinnati, Ohio, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Bronx VA Medical Center; 🇺🇸 Bronx, New York, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Mt. Sinai School of Medicine; 🇺🇸 New York, New York, United States

McGuire Hospital DVAMC; 🇺🇸 Richmond, Virginia, United States

VAMC - Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Advanced Liver Therapies - Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Tulane University Health Sciences Center; 🇺🇸 New Orleans, Louisiana, United States

Digestive Healthcare of Georgia; 🇺🇸 Atlanta, Georgia, United States