Standard of Care (SOC) With or Without CTS-1027 in Hepatitis C (HCV) Null-Responders
NCT ID: NCT01273064
Last Updated: 2012-06-11
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE2
114 participants
INTERVENTIONAL
2011-01-31
2011-10-31
Brief Summary
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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.
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Detailed Description
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Null-responders are defined as patients who failed to achieve a greater than 2 log drop in HCV-RNA 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 \< 2 log decline in HCV-RNA at Week 12 but \> 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.
The Principal Investigators, other site personnel, and patients will be blinded to the HCV-RNA results for the first 12 weeks of therapy.
At Week 12, the study treatment blind will be broken by the study's Interactive Web Randomization System (IWRS). However, the Principal Investigators, other investigative site personnel, patients, and Sponsor will remain blinded to treatment allocation until Week 24 (see below). The patients on the SOC + placebo arm will continue treatment as follows:
* Patients on SOC + placebo who do not achieve at least a 2 log decline in their HCV-RNA at Week 12 will be automatically rolled-over into the SOC + 15 mg CTS-1027 twice a day (BID) arm. The treatment duration for these patients will be 60 weeks (i.e., 12 weeks on SOC + placebo, followed by 48 weeks on SOC + 15 mg BID).
* Those patients on SOC + placebo who achieve ≥ 2 log decline at Week 12 will continue on SOC therapy until Week 48.
Patients in the SOC + CTS-1027 arms will continue with the same treatment regimen for the initial 24 weeks regardless of HCV-RNA changes.
At Week 24, the study blind will be formally broken. Patients will continue the study as follows:
* Patients in the SOC + CTS-1027 arms who achieve ≥ 2 log HCV-RNA decline by Week 24 will continue with the same treatment regimen they were assigned during the Double-Blind Phase for an additional 24 weeks.
* Patients in the SOC + CTS-1027 15 mg BID and the SOC + CTS-1027 30 mg BID arms who achieve a \<2 log HCV-RNA decline by Week 24 will escalate to the next higher dose of CTS-1027 for an additional 24 weeks.
* Patients in the SOC + CTS-1027 60 mg BID arm who do not achieve at least a 2 log HCV-RNA decline by Week 24 will be discontinued from the study.
All patients will be seen 4 and 12 weeks (Follow-Up Period) after the end of treatment. If a patient's HCV-RNA is undetectable at the end of treatment, he/she will be seen for an additional follow-up visit 24 weeks after the end of treatment.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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CTS-1027 60 mg + ribavirin + peglyated interferon
Standard 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
Supplied in 30mg, 10mg, or 5mg tablets (depending on dose arm) taken twice daily for up to 48 weeks.
pegylated interferon
180 micrograms in 0.5 ml of solution subcutaneously (SQ), delivered in single use syringes administered once per week, for up to 48 weeks.
Ribavirin
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
CTS-1027 30 mg + ribavirin + pegylated interferon
Standard 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
Supplied in 30mg, 10mg, or 5mg tablets (depending on dose arm) taken twice daily for up to 48 weeks.
pegylated interferon
180 micrograms in 0.5 ml of solution subcutaneously (SQ), delivered in single use syringes administered once per week, for up to 48 weeks.
Ribavirin
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
Placebo
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).
CTS-1027 15 mg + ribavirin + pegylated interferon
Standard 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.
CTS-1027
Supplied in 30mg, 10mg, or 5mg tablets (depending on dose arm) taken twice daily for up to 48 weeks.
pegylated interferon
180 micrograms in 0.5 ml of solution subcutaneously (SQ), delivered in single use syringes administered once per week, for up to 48 weeks.
Ribavirin
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
placebo + ribavirin + pegylated interferon
Standard 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.
pegylated interferon
180 micrograms in 0.5 ml of solution subcutaneously (SQ), delivered in single use syringes administered once per week, for up to 48 weeks.
Ribavirin
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
Placebo
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).
Interventions
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CTS-1027
Supplied in 30mg, 10mg, or 5mg tablets (depending on dose arm) taken twice daily for up to 48 weeks.
pegylated interferon
180 micrograms in 0.5 ml of solution subcutaneously (SQ), delivered in single use syringes administered once per week, for up to 48 weeks.
Ribavirin
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
Placebo
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).
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. 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
3. Screening HCV-RNA viral load of \> 5.0 log (i.e., \>100,000 IU/mL)
4. alpha-fetoprotein (AFP) less than or equal to 100 ng/mL
5. 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
6. Thyroid Stimulating Hormone (TSH) within normal limits
7. 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)
8. 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.
Exclusion Criteria
2. 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
3. Hepatic encephalopathy
4. Hepatocellular carcinoma (HCC) or suspicion of HCC clinically or on ultrasound (or other imaging techniques)
5. Clinically significant ocular findings such as retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or other abnormality
6. Known history or presence of human immunodeficiency virus (HIV) infection
7. Co-infection with hepatitis B virus (HBV)
8. If female: pregnant, lactating, or positive serum or urine pregnancy test
9. Male partners of women who are currently pregnant
10. Renal impairment (creatinine \> 1.2 x ULN), serum creatinine clearance \< 50 mL/min, or hepatorenal syndrome with ascites
11. Hospitalization for liver disease within 60 days of screening
12. History of alcohol abuse (\> 50 g per day) within the past year
13. History of severe psychiatric disease, especially depression, characterized by:
* Suicide attempt
* Hospitalization for psychiatric disease
* Period of disability as a result of psychiatric disease
14. Prior exposure to CTS-1027
15. Patients who qualify as a null-responder based on treatment(s) other than pegylated interferon and ribavirin
16. History or presence of clinically concerning cardiac arrhythmias or prolongation of pre-dose corrected Q-T interval (QTc) of \> 450 milliseconds
17. History of or current autoimmune disease
18. Diagnosis of or symptoms suggestive of fibromyalgia
19. Currently on liver transplantation waiting list or recipient of any organ transplant
20. 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 five or more years
21. Exposure to any other investigational treatment for any aspect of disease associated with HCV during the past 6 months
22. Exposure to any investigational drug or device within 30 days of dosing, or scheduled receipt of another investigational drug or device during the course of this study.
18 Years
ALL
No
Sponsors
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Conatus Pharmaceuticals Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Erin Castelloe, MD
Role: STUDY_CHAIR
Conatus Pharmaceuticals Inc.
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Southern California Liver Centers
Coronado, California, United States
Scripps Clinic
La Jolla, California, United States
Loma Linda University MC
Loma Linda, California, United States
Huntington Medical Research Institute
Pasadena, California, United States
Medical Associates Research Group
San Diego, California, United States
UCSD
San Diego, California, United States
University of Colorado Denver
Aurora, Colorado, United States
Yale University School of Medicine
New Haven, Connecticut, United States
University of Miami
Miami, Florida, United States
Atlanta Medical Center, Inc.
Atlanta, Georgia, United States
Liver Center of Atlanta
Atlanta, Georgia, United States
Rush University Medical Center
Chicago, Illinois, United States
Loyola University
Maywood, Illinois, United States
Indiana University School of Medicine
Indianapolis, Indiana, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
University of Louisville
Louisville, Kentucky, United States
Tulane University Health Sciences Center
New Orleans, Louisiana, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, United States
Henry Ford Hospital
Detroit, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
St. Louis University
St Louis, Missouri, United States
Concorde Medical Group
New York, New York, United States
New York University
New York, New York, United States
Weill Medical College of Cornell
New York, New York, United States
Columbia Presbyterian Medical Center
New York, New York, United States
Einstein College of Medicine (Jacobi Medical Center)
The Bronx, New York, United States
New York Medical College
Valhalla, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
Consultants for Clinical Research
Cincinnati, Ohio, United States
Cleveland Clinic
Cleveland, Ohio, United States
Albert Einstein Medical Center
Philadelphia, Pennsylvania, United States
Baylor All Saints Medical Center
Fort Worth, Texas, United States
University of Texas Medical Branch at Galveston
Galveston, Texas, United States
Research Specialists of Texas
Houston, Texas, United States
St. Luke's Episcopal Hospital
Houston, Texas, United States
University of Texas HSC at Houston
Houston, Texas, United States
VAMC Houston
Houston, Texas, United States
University of Utah
Salt Lake City, Utah, United States
Metropolitan Research Group Washington DC
Fairfax, Virginia, United States
Liver Institute of Virginia
Newport News, Virginia, United States
Virginia Commonwealth University (VCU)
Richmond, Virginia, United States
Benaroya Research Institute at Virginia Mason
Seattle, Washington, United States
Countries
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Other Identifiers
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CTS-1027-05
Identifier Type: -
Identifier Source: org_study_id
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