Clinical trial NCT00911963: Pharmacokinetics of Multiple Ascending Doses of VCH-222 in Subjects With Chronic Hepatitis C Infection
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hepatitis C
Keywords: VX-222
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
Collaborators: name: ViroChem Pharma
First posted: 2009-06-03
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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)
timeFrame: Daily for the first 3 days and at each study visit
measure: 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)
timeFrame: Week 4 and Week 12
measure: Assess the safety and tolerability of VCH-222 when administered in combination with Peg-IFN-alfa-2a/RBV for 12 weeks (Part B)
timeFrame: Study visits throughout part B
Secondary outcomes:
measure: To assess the safety and tolerability of VCH-222 when administered for 3 days in monotherapy (Part A)
timeFrame: Study visits throughout Part A
measure: To evaluate the pharmacokinetic (PK) profile of VCH-222 in HCV infected subjects (Part B)
timeFrame: Time points through Part B
Other outcomes:
Locations:
city: Marietta
country: United States
facility: Gastrointestinal Specialists of Georgia PC
state: Georgia
city: Detroit
country: United States
facility: Henry Ford Health Sytem
state: Michigan
city: Dallas
country: United States
facility: The liver institute at Methodist hospital
state: Texas
city: San Antonio
country: United States
facility: Alamo Medical Research
state: Texas
city: Buenos Aires
country: Argentina
facility: ACLIRES Argentina SRL
city: Buenos Aires
country: Argentina
facility: Hospital Universitario Austral
city: Vancouver
country: Canada
facility: Downtown ID Clinic/University of British Columbia
state: British Columbia
city: Winnipeg
country: Canada
facility: John Buhler Research Centre
state: Manitoba
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Santurce
country: Puerto Rico
facility: Fundacion de Investigation de Diego
Study officials:
affiliation: Vertex Pharmaceuticals Incorporated
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Jiang M, Zhang EZ, Ardzinski A, Tigges A, Davis A, Sullivan JC, Nelson M, Spanks J, Dorrian J, Nicolas O, Bartels DJ, Rao BG, Rijnbrand R, Kieffer TL. Genotypic and phenotypic analyses of hepatitis C virus variants observed in clinical studies of VX-222, a nonnucleoside NS5B polymerase inhibitor. Antimicrob Agents Chemother. 2014 Sep;58(9):5456-65. doi: 10.1128/AAC.03052-14. Epub 2014 Jun 30.