CTS-1027 in Interferon-Naive Hepatitis C Patients

Study Overview
=================
Brief Summary
-----------------
The study is intended to determine whether CTS-1027 either alone or in combination with ribavirin is safe and effective in Hepatitis C patients who have not previously been treated with interferon.

Detailed Description
-----------------
There are approximately 1 million Hepatitis C (HCV) patients in the US who have failed to respond to, or cannot tolerate, interferon or interferon plus ribavirin therapy. Significant adverse effects of interferon therapy include bone marrow depression (with reduced white blood cell and platelet counts) and major psychiatric disorders (especially depression). Ribavirin is associated with hemolytic anemia in a minority of patients who are treated with it. Patients with chronic HCV infection have a very low incidence of spontaneous viral clearance, have progressive disease, and have a continuing medical need for more efficacious and safer therapy. There is a significant unmet medical need for therapy in HCV patients who cannot (or will not) tolerate interferon-based treatment. This trial will evaluate the effects of CTS-1027 with or without ribavirin in patients who are previously untreated with interferon including patients with major psychiatric disorders, uncontrolled autoimmune disease, and patients who simply decline treatment.

Official Title
-----------------
A Trial of CTS-1027 in Interferon-Naive Hepatitis C Patients

Conditions
-----------------
Hepatitis C

Intervention / Treatment
-----------------
* Drug: ribavirin
* Drug: CTS-1027
* Drug: Placebo for ribavirin


Participation Criteria
=================
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 A history of chronic (> 6 months duration) genotype 1 Hepatitis C (HCV) infection Unsuitable for interferon-based HCV treatment, defined as at least one of the following three criteria: Contra-indicated for interferon treatment due to current or prior psychiatric disorders Patient's decision to not pursue interferon-based therapy In the opinion of the Principal Investigator, the patient is not a suitable candidate for interferon-based therapy a-fetoprotein (AFP) <= 50 ng/mL Hemoglobin ≥ 12 g/dL, platelet count ≥ 100 x 109/L, and white blood cell count ≥ 1.5 x 109/L 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: Decompensated or severe liver disease defined by one or more of the following criteria: Prothrombin time 3 seconds > control Direct bilirubin ≥ 1.5 x upper limit of normal range (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 Prior therapy for HCV with an interferon-based regimen Hepatocellular carcinoma (HCC) or suspicion of HCC clinically or on ultrasound (or other imaging techniques) Known history or presence of human immunodeficiency virus (HIV) infection Co-infection with hepatitis B virus (HBV) If female: pregnant, lactating, or positive serum pregnancy test Renal impairment (creatinine > 1.5 x ULN), creatinine clearance < 50 mL/min, or hepatorenal syndrome Hospitalization for liver disease within 60 days of screening Use of concomitant or prior drug therapy for HCV three months prior to screening Use of drugs of abuse in the prior three months (allowed if medically prescribed or indicated) History of alcohol abuse (> 50 g per day) within the past year History or presence of clinically concerning cardiac arrhythmias or prolongation of pre-dose QT or 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CTS-1027 + ribavirin<br>Study drug plus ribavirin | Drug: ribavirin<br>* 200 mg capsules, either 1000 or 1200 mg taken twice daily for up to 24 weeks<br>* Other names: Copegus;Drug: CTS-1027<br>* 5 and 10 mg tablets, 15 mg taken twice daily, for up to 24 weeks<br>|
| Experimental: CTS-1027 + placebo<br>Study drug plus placebo for ribavirin | Drug: CTS-1027<br>* 5 and 10 mg tablets, 15 mg taken twice daily, for up to 24 weeks<br>Drug: Placebo for ribavirin<br>* Capsules identical to ribavirin in appearance containing inactive ingredients<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in HCV-RNA (Hepatitis C Virus Ribonucleic Acid) Levels From Baseline Through 24 Weeks of Treatment | Measure the mean absolute changes in HCV-RNA (Hepatitis C virus ribonucleic acid, also known as viral load) levels in the blood from before treatment (baseline) through 24 weeks of treatment. Mean Absolute Change in HCV-RNA (log) = log10(HCV-RNA Week 24) - log10(HCV-RNA Baseline) | Baseline and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Aminotransferases From Baseline to 24 Weeks of Treatment | Mean absolute changes in ALT (alanine aminotransferase)in the blood from before treatment (baseline)through 24 weeks of treatment are presented. Mean absolute change in ALT (IU/ml)= ALT(Week 24) - ALT(baseline) | Baseline and 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HCV, interferon-naive