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

NCT00911963 | Completed Phase 1 DMC

• 1 other identifier: VCH-222-102
• Study Type: interventional
• Target: 49
• Locations: 4 countries
• Sites: 10

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.

Conditions

Hepatitis C

Keywords

VX-222

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• 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

Study Arms (2)

Part A

EXPERIMENTAL

This will be a 4 dose escalation study comparing VCH-222 to placebo treatment.

Drug: VCH-222 or matching placebo

Part B

EXPERIMENTAL

VCH-222 + peginterferon alfa-2a + ribavirin (12 weeks) followed by peginterferon alfa-2a + ribavirin for 36 weeks

Drug: VCH-222 or matching placebo; Biological: peginterferon alfa-2a; Drug: ribavirin

Interventions

VCH-222 or matching placebo DRUG

capsule, oral, 4 doses once daily or twice daily, 3 days

Also known as: VCH-222 is also known as VX-222

Part A

peginterferon alfa-2a BIOLOGICAL

subcutaneous injection, 180 μg, once weekly, 48 weeks

Part B

ribavirin DRUG

tablet, oral, 1000-1200 mg daily based on body weight, 48 weeks

Part B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead
• ViroChem Pharma: collaborator

Study Sites (10)

Gastrointestinal Specialists of Georgia PC

Marietta, Georgia, 30060, United States

Location

Henry Ford Health Sytem

Detroit, Michigan, 48202, United States

Location

The liver institute at Methodist hospital

Dallas, Texas, 75203, United States

Location

Alamo Medical Research

San Antonio, Texas, 78215, United States

Location

ACLIRES Argentina SRL

Buenos Aires, Argentina

Location

Hospital Universitario Austral

Buenos Aires, Argentina

Location

Downtown ID Clinic/University of British Columbia

Vancouver, British Columbia, V6Z 2C7, Canada

Location

John Buhler Research Centre

Winnipeg, Manitoba, R3E 3P4, Canada

Location

Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Fundacion de Investigation de Diego

Santurce, Puerto Rico

Location

Related Publications (1)

• 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.

  PMID: 24982088 DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

lomibuvir; peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Medical Monitor

  Vertex Pharmaceuticals Incorporated

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2009
• First Posted: June 3, 2009
• Study Start: April 1, 2009
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: March 10, 2014

Record last verified: 2014-02

Locations

CA (3); PR (1); US (4); AR (2)