Study of CTS-1027 in Hepatitis C Patients

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

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

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C Virus Infection
• Intervention / Treatment: Drug: CTS-1027; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic
    • San Diego, California, United States, 92154
      • Kaiser Permanente
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Digestive Healthcare of Georgia
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • West Bloomfield, Michigan, United States, 48322
      • Henry Ford Health System
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • Bronx, New York, United States, 10468
      • Bronx VA Medical Center
    • New York, New York, United States, 10019
      • Mt. Sinai School of Medicine
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Consultants of Clinical Research
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Texas
    • Houston, Texas, United States, 77030
      • Advanced Liver Therapies - Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • VAMC - Baylor College of Medicine
  • Virginia
    • Richmond, Virginia, United States, 23249
      • McGuire Hospital DVAMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	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.
Experimental: 2.5 milligram (mg) CTS-1027; 2.5 mg CTS-1027	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).
Experimental: 5 mg CTS-1027	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).
Experimental: 10 mg CTS-1027	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).
Experimental: 30 mg CTS-1027	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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
Peak and trough levels of CTS-1027 in plasma	4 to 24 weeks

Collaborators and Investigators

• Sponsor: Conatus Pharmaceuticals Inc.
• Collaborators: FGK Clinical Research GmbH
• Investigators: Study Director: William Frank, MD, Conatus Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: December 6, 2007
• First Submitted That Met QC Criteria: December 6, 2007
• First Posted (Estimate): December 10, 2007

Study Record Updates

• Last Update Posted (Estimate): September 16, 2010
• Last Update Submitted That Met QC Criteria: September 14, 2010
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: HCV; HCV treatment failure; Elevated aminotransferases
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic
• Other Study ID Numbers: CTS-1027-01