Study of CTS-1027 in Combination With Pegylated Interferon and Ribavirin in Hepatitis C Virus (HCV) Null-Responders (CTS-1027-04)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Conatus Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT01051921
First received: January 18, 2010
Last updated: April 10, 2012
Last verified: April 2012
  Purpose

The purpose of this study is to determine if the combination treatment of CTS-1027, pegylated interferon and ribavirin can improve the response rates in HCV patients who did not previously respond to pegylated interferon and ribavirin therapy.


Condition Intervention Phase
Hepatitis C
Drug: CTS-1027
Drug: Pegylated interferon
Drug: Ribavirin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Trial of Pegylated Interferon Plus Ribavirin in Combination With CTS-1027 in HCV Null-Responders

Resource links provided by NLM:


Further study details as provided by Conatus Pharmaceuticals Inc.:

Primary Outcome Measures:
  • Early Virologic Response (EVR) [ Time Frame: Baseline and Study week 12 ] [ Designated as safety issue: No ]
    Early Virologic Response (EVR) is defined as the percent of patients who experienced a drop in HCV-RNA (Hepatitis C Ribonucleic acid, also known as "viral load") levels of more that 2 log from before treatment (baseline) through 12 Weeks of treatment.


Secondary Outcome Measures:
  • > 2 Log Decline in Hepatitis C Virus Ribonucleic Acid (HCV-RNA) at 24 Weeks [ Time Frame: Baseline and Study week 24 ] [ Designated as safety issue: No ]
    Percent of patients experiencing a drop in HCV-RNA Hepatitis C virus ribonucleic acid, also known as "viral load") levels in the blood equal to, or greater than, 2 log from before treatment (baseline) through 24 weeks of treatment.


Enrollment: 67
Study Start Date: January 2010
Study Completion Date: December 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CTS-1027, Peg IFN, Ribavirin

Study drug (CTS-1027) plus Standard of Care treatment (pegylated interferon and ribavirin).

CTS-1027, 15 mg taken twice daily. Pegylated interferon, 180 μg injected once a week. Ribavirin, 1000 mg or 1200 mg daily (depending on patient weight), taken in two divided doses.

Drug: CTS-1027
CTS-1027 supplied in 5 and 10 mg tablets, 15 mg taken twice daily, for up to 48 weeks
Drug: Pegylated interferon
Pegylated interferon, 180 micrograms in 0.5 ml of solution injected subcutaneously (SQ) once per week, for up to 48 weeks. Packaged in single use syringes.
Other Name: Pegasys
Drug: Ribavirin
Ribavirin, 200 mg capsules taken in two divided daily doses totaling 1000 mg (5 capsules) for patients weighing 75 kg or less, or 1200 mg (6 capsules) for patients weighing more than 75 kg for up to 48 weeks.
Other Name: Copegus

Detailed Description:

A subset of non-responders to standard of care treatments (pegylated interferon and ribavrin) is termed null responders. Null responders are the most treatment refractory population. Treatment for null responders is currently limited: retreatment with SOC results in approximately 5% sustained virologic response (SVR).

CTS-1027 may facilitate the activity of interferon by preventing MMP-induced cleavage and deactivation in both phases of clinical response to therapy. In addition, CTS-1027, like ribavirin, alone does not significantly affect viral replication, but both CTS-1027 and ribavirin are likely to impact response to therapy during the second and slower phase of the clinical response.

The potential of MMP inhibition to facilitate the action of interferon, together with ribavirin-driven up-regulation of interferon stimulated genes, has the potential to yield a potent host immune response in this highly resistant null-responder patient population. Again, since MMP inhibition is thought to target the second slower phase kinetics, the initial treatment duration in this trial will be 24 weeks.

This trial will evaluate the safety and efficacy of CTS-1027 combined with SOC in patients who did not previously respond to SOC therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  • HCV genotype 1 infected null responders to prior therapy comprised of pegylated interferon and ribavirin (standard of care, SOC) defined as:

    • Failure to achieve an early virologic response (< 2 log decline in HCV-RNA by Week 12), or
    • If Week 12 HCV-RNA was not obtained but Week 24 was obtained, Week 24 response was < 2 log decline
  • Alpha-fetoprotein (AFP) <= 50 ng/mL
  • Hemoglobin ≥ 12 g/dL, platelet count ≥ 125 x 10^9/L, and white blood cell count ≥ 1.5 x 10^9/L
  • In the opinion of the Principal Investigator, the patient met the 80%/80%/80% rule during the previous pegylated interferon and ribavirin therapy (i.e., received at least 80% of the pegylated interferon and ribavirin doses, at least 80% of the dose size, for at least 80% of the treatment duration)
  • 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:

  • < 2 log decline in HCV-RNA at Week 12 but > 2 log decline at any time from Week 12 to Week 24 during prior therapy with pegylated interferon and ribavirin (prior standard of care therapy)
  • Decompensated or severe liver disease defined by one or more of the following criteria:

    • Prothrombin time 3 seconds > control
    • Direct bilirubin ≥ 1.5 x ULN
    • Serum albumin below normal limits
    • AST or ALT > 7 x ULN at screening
  • Evidence of portal hypertension including:

    • Varices on esophagogastroduodenoscopy (EGD) with or without a history of gastrointestinal bleeding; or
    • Ascites
  • Cirrhosis defined by one or both of the following criteria:

    • Liver biopsy showing cirrhosis
    • Other clinical signs and symptoms suggestive of cirrhosis
  • Hepatocellular carcinoma (HCC) or suspicion of HCC clinically or on ultrasound (or other imaging techniques)
  • Clinically significant ocular findings such as retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or other abnormality
  • 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
  • Male partners of women who are currently pregnant
  • Renal impairment (creatinine > 1.5 x ULN), creatinine clearance < 50 mL/min, or hepatorenal syndrome with ascites
  • Hospitalization for liver disease within 60 days of screening
  • History of alcohol abuse (> 50 g per day) within the past year
  • History of severe psychiatric disease, especially depression, characterized by:

    • Suicide attempt
    • Hospitalization for psychiatric disease
    • Period of disability as a result of psychiatric disease
  • Prior exposure to CTS-1027
  • Prior triple treatment comprised of pegylated interferon, ribavirin, and protease and/or polymerase inhibitors
  • History or presence of clinically concerning cardiac arrhythmias or prolongation of pre-dose 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01051921

Locations
United States, California
Scripps Clinic
La Jolla, California, United States, 92037
VA Medical Center, San Diego
San Diego, California, United States, 92161
United States, Colorado
University of Colorado Health Science Center
Denver, Colorado, United States, 80262
South Denver Gastroenterology
Englewood, Colorado, United States, 80113
United States, Georgia
Digestive Healthcare of Georgia
Atlanta, Georgia, United States, 30309
United States, Louisiana
Tulane University Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Michigan
Henry Ford Medical Center-Columbus
Novi, Michigan, United States, 48377
United States, Minnesota
MN Clinical Research Center
Plymouth, Minnesota, United States, 55446
United States, Missouri
St. Louis University
St. Louis, Missouri, United States, 63104
United States, Ohio
Consultants of Clinical Research, Ohio GI and Liver Institute
Cincinnati, Ohio, United States, 45219
United States, Texas
Advanced Liver Therapies - Baylor College of Medicine
Houston, Texas, United States, 77030
VA Medical Center, Houston
Houston, Texas, United States, 77030
United States, Utah
University of Utah Health Science Center
Salt Lake City, Utah, United States, 84132
United States, Virginia
Liver Institute of Virginia
Newport News, Virginia, United States, 23602
Puerto Rico
Fundacion de Investigacion de Diego
Santurce, Puerto Rico, 00909
Sponsors and Collaborators
Conatus Pharmaceuticals Inc.
Investigators
Study Chair: Erin Castelloe, MD Conatus Pharmaceuticals
  More Information

No publications provided

Responsible Party: Conatus Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT01051921     History of Changes
Other Study ID Numbers: CTS-1027-04
Study First Received: January 18, 2010
Results First Received: March 13, 2012
Last Updated: April 10, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Conatus Pharmaceuticals Inc.:
HCV
Null Responder

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferons
Ribavirin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014