Safety,Tolerability and Pharmacokinetics of Multiple Ascending Doses of VCH 916 in Subjects With Chronic Hep C Infection

A Phase 1B, Multicentre, Randomized, Double-Blinded, and PLacebo-Controlled Study of the Antiviral Activity, Safety, Tolerability, and PK of Multiple Ascending Doses of VCH-916 in the Treatment Naive or Experienced Subjects With Chronic Hep C-Infection.

The purpose of this study is to determine whether a 3-day course of therapy with orally administered VCH-916 given at different dosages can effectively reduce the amount of circulating virus (i.e., viral load) in patients with early-stage chronic hepatitis C-infection. This study will also evaluate the safety and tolerability of treatment with VCH-916. Blood samples will also be taken to measure the levels of VCH-916 present in plasma at various time points during the treatment period.

Study Overview

• Status: Completed
• Conditions: HCV Infection
• Intervention / Treatment: Drug: VCH 916; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital - General Campus
  • Quebec
    • Montréal, Quebec, Canada, H3A 1A1
      • Royal Victoria Hospital
• Puerto Rico
  • Santurce, Puerto Rico, 00909
    • Fundacion de Investigacion de Diego
• United States
  • Texas
    • Dallas, Texas, United States, 75208
      • The Liver Institute At Methodist Dallas
    • San Antonio, Texas, United States, 78215
      • Alamo Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females 18 to 60 years of age
• No evidence of cirrhosis or have liver fibrosis corresponding to Metavir Stages 0 to 3
• Subject's liver disease is stable with ALT values < 5 X ULN
• Serologic evidence of detectable plasma HCV-RNA of ≥ 100,000 IU/ml at screening
• Documented HCV Genotype 1 chronic hepatitis C.
• Judged to be in good health on the basis of medical history and physical examination
• All other hematology and clinical chemistry must be within normal limits or show no clinically significant abnormalities.
• Be treatment-naïve or experienced.
• For female subjects, must not be pregnant or breastfeeding and must be postmenopausal, surgically sterile, abstinent, or using two proven methods of birth control.
• Sexually active male subjects, must be practicing acceptable methods of contraception during the treatment period
• Female subjects of childbearing potential must have a negative serum ß-HCG pregnancy test at screening and a negative urine pregnancy test on Day 1 before the first dose of study drugs.
• Agree not to participate in other clinical trials for the duration of his/her participation in this clinical trial.

Exclusion Criteria:

• Be participating in any other clinical studies or have participated in another clinical trial within the last 30 days before study drug administration, or participation in more than 2 drug studies in the last 12 months (exclusive of the current study).
• Be actively taking hard illicit drugs within 12 months prior to the screening visit or alcohol.
• Have a Child-Pugh score > than 5.
• Have evidence of liver cirrhosis including histological evidence of hepatic cirrhosis on any liver biopsy.
• Have any cause of liver disease other than chronic hepatitis C-infection
• Active or malignant disease or suspicion or history of malignant disease within five previous years (except for adequately treated basal cell carcinoma).
• Have clinically significant electrocardiogram abnormalities and/or cardiovascular dysfunction within the previous 6 months
• Have significant renal, pulmonary, gastrointestinal absorption, or neurological diseases, or neoplasia.
• Have a history of psychiatric disorders determined by the investigator to contraindicate therapy.
• Have uncontrolled Type 1 or Type II diabetes.
• Antinuclear antibody titer ≥1:320.
• Coinfection with hepatitis B and/or HIV 1 or HIV 2.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; VCH-916 100 mg three times a day (t.i.d.)	Drug: VCH 916; Dose escalation study with a full review of all safety data following each cohort.; Drug: Placebo; Dose escalation study with a full review of all safety data following each cohort.
Experimental: Cohort 2; VCH-916 200 mg (t.i.d.)	Drug: VCH 916; Dose escalation study with a full review of all safety data following each cohort.; Drug: Placebo; Dose escalation study with a full review of all safety data following each cohort.
Experimental: Cohort 3; VCH-916 300 mg twice daily for three days	Drug: VCH 916; Dose escalation study with a full review of all safety data following each cohort.; Drug: Placebo; Dose escalation study with a full review of all safety data following each cohort.
Experimental: cohort 4; VCH-916 400 mg twice daily for three days	Drug: VCH 916; Dose escalation study with a full review of all safety data following each cohort.; Drug: Placebo; Dose escalation study with a full review of all safety data following each cohort.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary objective of this trial is to assess the antiviral activity, safety, and tolerability of VCH-916 monotherapy in adult subjects with chronic HCV-infection.	Day 1 to Day 17 visits

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the pharmacokinetic (PK) profile of VCH-916 in HCV-infected adults.	Day 1 visit
To establish the relationship between VCH-916 plasma levels and corresponding HCV RNA reduction with the administered dosages of VCH-916 in adults.	Day 1 to Day 4 visits
To study the kinetics of plasma HCV RNA following treatment for up to three(3) days with VCH-916.	Day 1 to Day 4 visits

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated
• Collaborators: Duke Clinical Research Institute; ViroChem Pharma
• Investigators: Principal Investigator: John McHutchison, MD, Duke Clinical Research Institute

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: February 14, 2008
• First Submitted That Met QC Criteria: February 25, 2008
• First Posted (Estimate): February 26, 2008

Study Record Updates

• Last Update Posted (Estimate): April 4, 2014
• Last Update Submitted That Met QC Criteria: April 2, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Infections; Communicable Diseases; Hepatitis C
• Other Study ID Numbers: VCH 916-103