Pharmacokinetics of Multiple Ascending Doses of VCH-222 in Subjects With Chronic Hepatitis C Infection

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess antiviral activity when administered alone for 3 days or in combination with peginterferon and ribavirin for 12 weeks. This study will also evaluate the safety and tolerability of treatment with VCH-222 when given alone or in combination with peginterferon and ribavirin. The study will also evaluate the pharmacokinetic profile of VCH-222 in HCV infected subjects.

Official Title
-----------------
A Phase l b/II a, Multicenter, Randomized, Double-Blinded, and Placebo-Controlled Study of the Antiviral Activity, Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of VCH-222 in Subjects With Chronic Hepatitis C-Infection

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

Intervention / Treatment
-----------------
* Drug: VCH-222 or matching placebo
* Drug: VCH-222 or matching placebo
* Biological: peginterferon alfa-2a
* Drug: ribavirin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and Female subjects, 18-65 years of age (females non-child bearing potential in Part B) Have laboratory evidence of HCV infection for 6 months, defined by (1) presence of anti-HCV antibody (Genotype 1a and 1b infection), or (2)documented HCV RNA presence by a sensitive and specific assay and (3 histologic evidence of CHC (Fibrosis on a standardized histological grading system) Plasma HCV RNA of 100,000 IU/ml HIV 1 and HIV2 ab seronegative Body Mass Index (BMI) ≤ 35 kg/m2 BMI Treatment Naive subjects Exclusion Criteria: Contraindications to peginterferon or ribavirin therapy Have evidence of liver cirrhosis, decompensated liver disease, and Child-Pugh score > 5 Have hemoglobinopathies, unstable cardiac disease, history of organ transplant, active malignant disease or uncontrolled Type I or II diabetes

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A<br>This will be a 4 dose escalation study comparing VCH-222 to placebo treatment. | Drug: VCH-222 or matching placebo<br>* capsule, oral, 4 doses once daily or twice daily, 3 days<br>* Other names: VCH-222 is also known as VX-222;|
| Experimental: Part B<br>VCH-222 + peginterferon alfa-2a + ribavirin (12 weeks) followed by peginterferon alfa-2a + ribavirin for 36 weeks | Drug: VCH-222 or matching placebo<br>* capsule, oral, 400 mg twice daily or 750 mg twice daily, 12 weeks<br>* Other names: VCH-222 is also known as VX-222;Biological: peginterferon alfa-2a<br>* subcutaneous injection, 180 μg, once weekly, 48 weeks<br>Drug: ribavirin<br>* tablet, oral, 1000-1200 mg daily based on body weight, 48 weeks<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the antiviral activity of VCH-222, in subjects with genotype 1 hepatitis C virus (HCV) infection after once (QD) or twice (b.i.d.) daily dosing for 3 days (Part A) |  | Daily for the first 3 days and at each study visit | 
| To assess the antiviral activity of VCH-222, in subjects with genotype 1 HCV infection after b.i.d. daily dosing for 12 weeks in combination with Peg-interferon-alfa-2a and ribavirin (Part B) |  | Week 4 and Week 12 | 
| Assess the safety and tolerability of VCH-222 when administered in combination with Peg-IFN-alfa-2a/RBV for 12 weeks (Part B) |  | Study visits throughout part B | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability of VCH-222 when administered for 3 days in monotherapy (Part A) |  | Study visits throughout Part A | 
| To evaluate the pharmacokinetic (PK) profile of VCH-222 in HCV infected subjects (Part B) |  | Time points through Part B | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
VX-222