Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Voxilaprevir in Adults With Chronic Hepatitis C Virus Infection

Phase 1

Completed

• Conditions: Hepatitis C Virus Infection
• Interventions: Drug: Voxilaprevir; Drug: Placebo to match voxilaprevir; Drug: SOF/VEL

• Registration Number: NCT02185794
• Lead Sponsor: Gilead Sciences

Brief Summary

The primary objective of the study is to evaluate the safety and tolerability of voxilaprevir (formerly GS-9857) alone or with sofosbuvir (SOF)/velpatasvir (VEL) fixed dose combination (FDC) and antiviral activity of voxilaprevir in adults with genotype 1, 2, 3, 4 hepatitis C virus (HCV) infection. All participants will be monitored for up to 48 weeks after the last dose.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-06-13
• Study First Submitted: 2014-07-07
• Study First Submitted QC: 2014-07-07
• Study First Posted: 2014-07-10
• Primary Completion: 2014-12-22
• Study Completion: 2015-09-28
• Status Verified: 2020-08
• Results First Submitted: 2020-08-06
• Results First Submitted QC: 2020-08-06
• Results First Posted: 2020-08-21
• Last Update Submitted: 2020-08-28
• Last Update Posted: 2020-09-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 101

Inclusion Criteria

• Chronic genotype 1-4 HCV infection
• For Cohorts 1-9, HCV RNA ≥ 100,000 IU/mL at screening (no HCV RNA restriction for Cohort 10)
• Screening laboratory values within defined thresholds
• Use of two effective contraception methods if female of childbearing potential or sexually active male

Key

Exclusion Criteria

• Pregnant or nursing female or male with pregnant female partner
• Presence of cirrhosis
• Prior exposure to approved or experimental HCV Protease Inhibitors
• Co-infection with HIV or hepatitis B virus (HBV)
• Current or prior history of clinical hepatic decompensation
• Chronic use of systemic immunosuppressive agents
• History of clinically significant illness or any other medical disorder that may interfere with participant's treatment, assessment or compliance with the protocol

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Voxilaprevir 100 mg (GT 1b, Cohort 5)	Voxilaprevir	Participants with GT 1b HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.
Voxilaprevir 100 mg Fed (GT 3a, Cohort 6)	Voxilaprevir	Participants with GT 3a HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fed conditions.
Placebo (GT 1a, Cohort 1)	Placebo to match voxilaprevir	Participants with genotype (GT) 1a HCV infection will receive placebo once daily for 3 days under fasted conditions.
Voxilaprevir 50 mg (GT 1a, Cohort 1)	Voxilaprevir	Participants with GT 1a HCV infection will receive voxilaprevir 50 mg once daily for 3 days under fasted conditions.
Voxilaprevir 100 mg (GT 1a, Cohort 1)	Voxilaprevir	Participants with GT 1a HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.
Placebo (GT 3, Cohort 2)	Placebo to match voxilaprevir	Participants with GT 3 HCV infection will receive placebo once daily for 3 days under fasted conditions.
Placebo (GT 2, Cohort 3)	Placebo to match voxilaprevir	Participants with GT 2 HCV infection will receive placebo once daily for 3 days under fasted conditions.
Voxilaprevir 600 mg (Cohorts 7-9)	Voxilaprevir	Participants with genotypes 1a, 1b, 2, 3, or 4 HCV infection will receive voxilaprevir up to 600 mg under fasted or fed conditions for 3 days.
Voxilaprevir 100 mg + SOF/VEL 400/100 mg (Group 1, Cohort 10)	Voxilaprevir	Participants with any GT HCV infection received voxilaprevir 100 mg on Day 1 after moderate fat meal and voxilaprevir 100 mg plus sofosbuvir (SOF)/velpatasvir (VEL) (400/100 mg) fixed-dose combination (FDC)on Days 2 and 3 after either a light or moderate-fat meal.
Voxilaprevir 100 mg + SOF/VEL 400/100 mg (Group 1, Cohort 10)	SOF/VEL	Participants with any GT HCV infection received voxilaprevir 100 mg on Day 1 after moderate fat meal and voxilaprevir 100 mg plus sofosbuvir (SOF)/velpatasvir (VEL) (400/100 mg) fixed-dose combination (FDC)on Days 2 and 3 after either a light or moderate-fat meal.
Voxilaprevir 100 mg + SOF/VEL 400/100 mg (Group 2, Cohort 10)	Voxilaprevir	Participants with any GT HCV infection received voxilaprevir 100 mg on Day 1 and voxilaprevir 100 mg plus SOF/VEL (400/100 mg) FDC on Days 2 and 3 after moderate fat meal.
Voxilaprevir 100 mg + SOF/VEL 400/100 mg (Group 2, Cohort 10)	SOF/VEL	Participants with any GT HCV infection received voxilaprevir 100 mg on Day 1 and voxilaprevir 100 mg plus SOF/VEL (400/100 mg) FDC on Days 2 and 3 after moderate fat meal.
Voxilaprevir 300 mg (GT 1a, Cohort 1)	Voxilaprevir	Participants with GT 1a HCV infection will receive voxilaprevir 300 mg once daily for 3 days under fasted conditions.
Voxilaprevir 50 mg (GT 3, Cohort 2)	Voxilaprevir	Participants with GT 3 HCV infection will receive voxilaprevir 50 mg once daily for 3 days under fasted conditions.
Voxilaprevir 300 mg (GT 3, Cohort 2)	Voxilaprevir	Participants with GT 3 HCV infection will receive voxilaprevir 300 mg once daily for 3 days under fasted conditions.
Voxilaprevir 100 mg (GT 3, Cohort 2)	Voxilaprevir	Participants with GT 3 HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.
Voxilaprevir 100 mg (GT 2, Cohort 3)	Voxilaprevir	Participants with GT 2 HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.
Voxilaprevir 100 mg (GT 4, Cohort 4)	Voxilaprevir	Participants with GT 4 HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing Treatment Emergent Adverse Events	First dose date up to Day 3 plus 30 days
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities	First dose date up to Day 3 plus 30 days	Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The severity of laboratory abnormalities was assessed as Grade 0, 1 (mild), 2 (moderate), 3 (severe), or 4 (potentially life threatening) using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. The most severe graded abnormality from all tests was counted for each participant.
Antiviral Activity of Voxilaprevir as Measured by Change From Baseline in Plasma HCV RNA	Baseline; Days 4, 5, 6, 7, 8, 10, and Week 48	The outcome measure was assessed to evaluate antiviral activity of voxilaprevir only (cohorts 1 through 6). Data are summarized by treatment/cohort and placebo.

Secondary Outcome Measures

Name	Time	Method
Antiviral Activity of Voxilaprevir as Measured by Number of Participants Achieving Reductions From Baseline in HCV RNA	Baseline; Days 4, 5, 6, 7, 8, 10, and Week 48	Categorical declines from baseline were summarized by the number of participants with a \< 1, ≥ 1 to \<2, ≥ 2 to \<3, or ≥ 3 log10 IU/mL decrease in HCV RNA from baseline to each postdose assessment up to Week 48 by treatment/cohort and placebo. The outcome measure was assessed to evaluate antiviral activity of voxilaprevir only (cohorts 1 through 6).
Percentage of Participants Who Have HCV RNA < Lower Limit of Quantitation (LLOQ) Detected, and < LLOQ Target Not Detected (TND)	Days 4, 5, 6, 7, 8, 10, and Week 48	The lower limit of quantitation (LLOQ) detection for HCV RNA levels was 15 IU/mL. HCV detected means calculated HCV RNA level is below LLOQ of the assay. The outcome measure was assessed to evaluate antiviral activity of voxilaprevir only (cohorts 1 through 6).
Antiviral Activity of Voxilaprevir as Measured by Absolute HCV RNA Level Through Week 48	Baseline (Pre Day 1 Dose); Days 4, 5, 6, 7, 8, 10, and Week 48	The outcome measure was assessed to evaluate antiviral activity of voxilaprevir only (cohorts 1 through 6).