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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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HCV Infection

Intervention / Treatment
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* Drug: VCH 916
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |