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

Primary Purpose

Hepatitis C

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
CTS-1027
Pegylated interferon
Ribavirin
Sponsored by
Conatus Pharmaceuticals Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C focused on measuring HCV, Null Responder

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Scripps Clinic
  • VA Medical Center, San Diego
  • University of Colorado Health Science Center
  • South Denver Gastroenterology
  • Digestive Healthcare of Georgia
  • Tulane University Health Sciences Center
  • Henry Ford Medical Center-Columbus
  • MN Clinical Research Center
  • St. Louis University
  • Consultants of Clinical Research, Ohio GI and Liver Institute
  • Advanced Liver Therapies - Baylor College of Medicine
  • VA Medical Center, Houston
  • University of Utah Health Science Center
  • Liver Institute of Virginia
  • Fundacion de Investigacion de Diego

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CTS-1027, Peg IFN, Ribavirin

Arm Description

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.

Outcomes

Primary Outcome Measures

Early Virologic Response (EVR)
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
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.

Full Information

First Posted
January 18, 2010
Last Updated
April 10, 2012
Sponsor
Conatus Pharmaceuticals Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01051921
Brief Title
Study of CTS-1027 in Combination With Pegylated Interferon and Ribavirin in Hepatitis C Virus (HCV) Null-Responders
Acronym
CTS-1027-04
Official Title
An Open-Label Trial of Pegylated Interferon Plus Ribavirin in Combination With CTS-1027 in HCV Null-Responders
Study Type
Interventional

2. Study Status

Record Verification Date
April 2012
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Conatus Pharmaceuticals Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C
Keywords
HCV, Null Responder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
67 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CTS-1027, Peg IFN, Ribavirin
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
CTS-1027
Intervention Description
CTS-1027 supplied in 5 and 10 mg tablets, 15 mg taken twice daily, for up to 48 weeks
Intervention Type
Drug
Intervention Name(s)
Pegylated interferon
Other Intervention Name(s)
Pegasys
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Other Intervention Name(s)
Copegus
Intervention Description
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.
Primary Outcome Measure Information:
Title
Early Virologic Response (EVR)
Description
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.
Time Frame
Baseline and Study week 12
Secondary Outcome Measure Information:
Title
> 2 Log Decline in Hepatitis C Virus Ribonucleic Acid (HCV-RNA) at 24 Weeks
Description
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.
Time Frame
Baseline and Study week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Erin Castelloe, MD
Organizational Affiliation
Conatus Pharmaceuticals
Official's Role
Study Chair
Facility Information:
Facility Name
Scripps Clinic
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
VA Medical Center, San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92161
Country
United States
Facility Name
University of Colorado Health Science Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
South Denver Gastroenterology
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
Facility Name
Digestive Healthcare of Georgia
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Tulane University Health Sciences Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Henry Ford Medical Center-Columbus
City
Novi
State/Province
Michigan
ZIP/Postal Code
48377
Country
United States
Facility Name
MN Clinical Research Center
City
Plymouth
State/Province
Minnesota
ZIP/Postal Code
55446
Country
United States
Facility Name
St. Louis University
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Consultants of Clinical Research, Ohio GI and Liver Institute
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Advanced Liver Therapies - Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
VA Medical Center, Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah Health Science Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Liver Institute of Virginia
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23602
Country
United States
Facility Name
Fundacion de Investigacion de Diego
City
Santurce
ZIP/Postal Code
00909
Country
Puerto Rico

12. IPD Sharing Statement

Learn more about this trial

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

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