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

Information source: Conatus Pharmaceuticals Inc.
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Hepatitis C

Intervention: CTS-1027 (Drug); Pegylated interferon (Drug); Ribavirin (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Conatus Pharmaceuticals Inc.

Official(s) and/or principal investigator(s):
Erin Castelloe, MD, Study Chair, Affiliation: Conatus Pharmaceuticals

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.

Clinical Details

Official title: An Open-Label Trial of Pegylated Interferon Plus Ribavirin in Combination With CTS-1027 in HCV Null-Responders

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Early Virologic Response (EVR)

Secondary outcome: > 2 Log Decline in Hepatitis C Virus Ribonucleic Acid (HCV-RNA) at 24 Weeks

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Locations and Contacts

Fundacion de Investigacion de Diego, Santurce 00909, Puerto Rico

Scripps Clinic, La Jolla, California 92037, United States

VA Medical Center, San Diego, San Diego, California 92161, United States

University of Colorado Health Science Center, Denver, Colorado 80262, United States

South Denver Gastroenterology, Englewood, Colorado 80113, United States

Digestive Healthcare of Georgia, Atlanta, Georgia 30309, United States

Tulane University Health Sciences Center, New Orleans, Louisiana 70112, United States

Henry Ford Medical Center-Columbus, Novi, Michigan 48377, United States

MN Clinical Research Center, Plymouth, Minnesota 55446, United States

St. Louis University, St. Louis, Missouri 63104, United States

Consultants of Clinical Research, Ohio GI and Liver Institute, Cincinnati, Ohio 45219, United States

Advanced Liver Therapies - Baylor College of Medicine, Houston, Texas 77030, United States

VA Medical Center, Houston, Houston, Texas 77030, United States

University of Utah Health Science Center, Salt Lake City, Utah 84132, United States

Liver Institute of Virginia, Newport News, Virginia 23602, United States

Additional Information

Starting date: January 2010
Last updated: April 10, 2012

Page last updated: August 23, 2015

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