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
Overview
- Phase
- Phase 1
- Intervention
- VCH-222 or matching placebo
- Conditions
- Hepatitis C
- Sponsor
- Vertex Pharmaceuticals Incorporated
- Enrollment
- 49
- Locations
- 10
- Primary Endpoint
- 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)
- Status
- Completed
- Last Updated
- 12 years ago
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.
Investigators
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
Arms & Interventions
Part A
This will be a 4 dose escalation study comparing VCH-222 to placebo treatment.
Intervention: VCH-222 or matching placebo
Part B
VCH-222 + peginterferon alfa-2a + ribavirin (12 weeks) followed by peginterferon alfa-2a + ribavirin for 36 weeks
Intervention: VCH-222 or matching placebo
Part B
VCH-222 + peginterferon alfa-2a + ribavirin (12 weeks) followed by peginterferon alfa-2a + ribavirin for 36 weeks
Intervention: peginterferon alfa-2a
Part B
VCH-222 + peginterferon alfa-2a + ribavirin (12 weeks) followed by peginterferon alfa-2a + ribavirin for 36 weeks
Intervention: ribavirin
Outcomes
Primary Outcomes
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)
Time Frame: 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)
Time Frame: 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)
Time Frame: Study visits throughout part B
Secondary Outcomes
- 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)