Study Stopped
Risk-benefit ratio
Standard of Care (SOC) With or Without CTS-1027 in Hepatitis C (HCV) Null-Responders
A Placebo-Controlled, Multicenter, Double-Blind, Randomized Trial of Pegylated Interferon Plus Ribavirin With or Without CTS-1027 in HCV Null-Responders
1 other identifier
interventional
114
1 country
45
Brief Summary
Placebo controlled, double-blind, multicenter study utilizing standard of care (SOC) treatment (ribavirin plus pegylated interferon) in combination with CTS-1027 in genotype 1 chronic Hepatitis C (HCV) patients who were null-responders to previous SOC therapy(ies). Null-responders are defined as patients who failed to achieve a greater than 2 log drop in HCV-RNA (Hepatitis C Ribonucleic acid, also known as "viral load") levels after 12 weeks of treatment (know as an "early virologic response", or EVR) during previous SOC therapy. If, during previous SOC treatment, a patient had a less than 2 log decline in HCV-RNA at Week 12 but greater than 2 log decline in HCV-RNA at any time from Week 12 to Week 24, that patient is not a null-responder, and is excluded from study participation. If, during previous SOC treatment, a Week 12 HCV-RNA was not obtained, the post Week 12 response must have been \< 2 log decline (and still HCV-RNA positive) in order for the patient to be defined as a null-responder. Patients will be screened and have up to 4 weeks to qualify for study entry. During this screening period, clinical and laboratory tests will be performed. At Week 0/Day 1, patients will undergo centralized, stratified (based on ethnicity), randomization to one of four treatment arms: SOC + one of three doses of CTS-1027 or SOC + placebo. Study treatment will last 24, 48, or 60 weeks, based on each patient's response to study treatment. SOC + placebo patients who do not show a virologic response after 12 weeks of therapy will be rolled onto SOC + 15mg CTS-1027, while maintaining the study blind.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jan 2011
Shorter than P25 for phase_2
45 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 21, 2010
CompletedStudy Start
First participant enrolled
January 1, 2011
CompletedFirst Posted
Study publicly available on registry
January 10, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2011
CompletedResults Posted
Study results publicly available
May 30, 2012
CompletedJune 11, 2012
June 1, 2012
8 months
December 21, 2010
March 29, 2012
June 4, 2012
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Sustained Virologic Response
Percent of patients that achieve a sustained virologic response (SVR) at Week 72 defined as HCV-RNA (Hepatitis C virus ribonucleic acid, also known as 'viral load') level below the quantification limit (BQL) at Week 72.
Baseline and 24 weeks after the end of treatment (Week 72)
Secondary Outcomes (1)
Greater Than 2 Log Decline in HCV-RNA at Study Weeks 12, 24 and 48
Baseline, and Study Weeks 12, 24, and 48
Study Arms (4)
CTS-1027 60 mg + ribavirin + peglyated interferon
EXPERIMENTALStandard of Care (ribavirin plus pegylated interferon) plus CTS-1027, 60 mg (supplied in a blinded kit containing two bottles of 30 mg tablets). One tablet from each of the CTS bottles is taken twice daily, for a total daily dose of 120 mg.
CTS-1027 30 mg + ribavirin + pegylated interferon
EXPERIMENTALStandard of Care (ribavirin plus pegylated interferon) plus CTS-1027 30 mg, supplied in a blinded kit containing one bottle of 30 mg tablets, and one bottle of placebo tablets (in order to maintain blind). One tablet from each of the bottles is taken twice daily, for a total daily dose of 60 mg of CTS-1027.
CTS-1027 15 mg + ribavirin + pegylated interferon
EXPERIMENTALStandard of Care (ribavirin plus pegylated interferon) plus CTS-1027 15 mg (supplied in a blinded kit containing one bottle each of of 5 mg and 10 mg tablets). One tablet from each of the CTS bottles is taken twice daily, for a total daily dose of 30 mg.
placebo + ribavirin + pegylated interferon
ACTIVE COMPARATORStandard of Care (ribavirin plus pegylated interferon) plus placebo (supplied in a blinded kit containing two bottles of placebo tablets). One tablet is taken from each of the placebo bottles twice daily, for a total daily dose of 4 tablets.
Interventions
Supplied in 30mg, 10mg, or 5mg tablets (depending on dose arm) taken twice daily for up to 48 weeks.
180 micrograms in 0.5 ml of solution subcutaneously (SQ), delivered in single use syringes administered once per week, for up to 48 weeks.
200 mg capsules of ribavirn 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
Tablets identical in appearance to CTS-1027 containing inactive ingredients. Placebo arm patients: Two tablets taken twice daily, for a total daily dose of four tablets. 30 mg CTS-1027 patients: One tablet taken twice daily, for a total daily dose of two tablets. One bottle of placebo is added to the 30mg kits in order to maintain the study blind (all patients recieve two-bottle kits of CTS-1027 and/or placebo).
Eligibility Criteria
You may qualify if:
- 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 study
- 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, post Week 12 HCV-RNA response was \< 2 log decline
- Screening HCV-RNA viral load of \> 5.0 log (i.e., \>100,000 IU/mL)
- alpha-fetoprotein (AFP) less than or equal to 100 ng/mL
- Hemoglobin greater than or equal to 12 g/dL for women and greater than or equal to 13 g/dL for men, hemoglobin A1c less than or equal to 7.5 %, platelet count greater than or equal to 90 x 10\^9/L, and white blood cell count greater than or equal to 1.5 x 10\^9/L
- Thyroid Stimulating Hormone (TSH) within normal limits
- 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 study.
You may not qualify if:
- \< 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 4 seconds \> control or INR (international normalized ratio) \> 1.2
- Total bilirubin ≥ 1.5 mg/dL or direct bilirubin ≥ 1 mg/dL
- Serum albumin below normal limits
- aspartate aminotransferase (AST) or alanine aminotransferase (ALT)\> 5 x upper limit of normal (ULN) at screening
- Presence of ascites
- Hepatic encephalopathy
- 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 \> 1.2 x ULN), serum creatinine clearance \< 50 mL/min, or hepatorenal syndrome with ascites
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (45)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Southern California Liver Centers
Coronado, California, 92118, United States
Scripps Clinic
La Jolla, California, 92037, United States
Loma Linda University MC
Loma Linda, California, 92354, United States
Huntington Medical Research Institute
Pasadena, California, 91105, United States
Medical Associates Research Group
San Diego, California, 92123, United States
UCSD
San Diego, California, 92161, United States
University of Colorado Denver
Aurora, Colorado, 80045, United States
Yale University School of Medicine
New Haven, Connecticut, 06520, United States
University of Miami
Miami, Florida, 33136, United States
Atlanta Medical Center, Inc.
Atlanta, Georgia, 30309, United States
Liver Center of Atlanta
Atlanta, Georgia, 30309, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
Loyola University
Maywood, Illinois, 60153, United States
Indiana University School of Medicine
Indianapolis, Indiana, 46201, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
University of Louisville
Louisville, Kentucky, 40202, United States
Tulane University Health Sciences Center
New Orleans, Louisiana, 70112, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, 01655, United States
Henry Ford Hospital
Detroit, Michigan, 48202-2689, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
St. Louis University
St Louis, Missouri, 63104, United States
Concorde Medical Group
New York, New York, 10016, United States
New York University
New York, New York, 10016, United States
Weill Medical College of Cornell
New York, New York, 10021, United States
Columbia Presbyterian Medical Center
New York, New York, 10032, United States
Einstein College of Medicine (Jacobi Medical Center)
The Bronx, New York, 10461, United States
New York Medical College
Valhalla, New York, 10595, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Consultants for Clinical Research
Cincinnati, Ohio, 45219, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Albert Einstein Medical Center
Philadelphia, Pennsylvania, 19141, United States
Baylor All Saints Medical Center
Fort Worth, Texas, 76104, United States
University of Texas Medical Branch at Galveston
Galveston, Texas, 77555, United States
Research Specialists of Texas
Houston, Texas, 77030, United States
St. Luke's Episcopal Hospital
Houston, Texas, 77030, United States
University of Texas HSC at Houston
Houston, Texas, 77030, United States
VAMC Houston
Houston, Texas, 77030, United States
University of Utah
Salt Lake City, Utah, 84132, United States
Metropolitan Research Group Washington DC
Fairfax, Virginia, 22031, United States
Liver Institute of Virginia
Newport News, Virginia, 23602, United States
Virginia Commonwealth University (VCU)
Richmond, Virginia, 23298, United States
Benaroya Research Institute at Virginia Mason
Seattle, Washington, 98101, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
This study was terminated early after 3 reports of hyperbilirubinemia occurred(2 on 60mg bid and 1 on 30mg bid of CTS 1027). Two incidents were reported as part of an SAE. The risk/benefit ratio did not warrant further continuation of the study.
Results Point of Contact
- Title
- MiRa Huyghe, Vice President, Clinical Development
- Organization
- Conatus Pharmaceuticals Inc.
Study Officials
- STUDY CHAIR
Erin Castelloe, MD
Conatus Pharmaceuticals Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 21, 2010
First Posted
January 10, 2011
Study Start
January 1, 2011
Primary Completion
September 1, 2011
Study Completion
October 1, 2011
Last Updated
June 11, 2012
Results First Posted
May 30, 2012
Record last verified: 2012-06