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

August 28, 2020 updated by: Gilead Sciences

Phase 1b, Randomized, Double-Blind, Multiple-Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of GS-9857 in Subjects With Chronic Hepatitis C Virus Infection

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

101

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico
  • United States
    • California
      • Costa Mesa, California, United States
    • Florida
      • DeLand, Florida, United States
      • Orlando, Florida, United States
    • Missouri
      • Kansas City, Missouri, United States
      • Saint Louis, Missouri, United States
    • New Jersey
      • Berlin, New Jersey, United States
      • Marlton, New Jersey, United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
    • Tennessee
      • Knoxville, Tennessee, United States
    • Texas
      • San Antonio, Texas, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo (GT 1a, Cohort 1)
Participants with genotype (GT) 1a HCV infection will receive placebo once daily for 3 days under fasted conditions.
Drug: Placebo to match voxilaprevir
Placebo to match voxilaprevir tablets administered orally once daily
Experimental: Voxilaprevir 50 mg (GT 1a, Cohort 1)
Participants with GT 1a HCV infection will receive voxilaprevir 50 mg once daily for 3 days under fasted conditions.
Drug: Voxilaprevir
Voxilaprevir tablets administered orally once daily
Other Names:
  • GS-9857
Experimental: Voxilaprevir 100 mg (GT 1a, Cohort 1)
Participants with GT 1a HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.
Drug: Voxilaprevir
Voxilaprevir tablets administered orally once daily
Other Names:
  • GS-9857
Experimental: Voxilaprevir 300 mg (GT 1a, Cohort 1)
Participants with GT 1a HCV infection will receive voxilaprevir 300 mg once daily for 3 days under fasted conditions.
Drug: Voxilaprevir
Voxilaprevir tablets administered orally once daily
Other Names:
  • GS-9857
Placebo Comparator: Placebo (GT 3, Cohort 2)
Participants with GT 3 HCV infection will receive placebo once daily for 3 days under fasted conditions.
Drug: Placebo to match voxilaprevir
Placebo to match voxilaprevir tablets administered orally once daily
Experimental: Voxilaprevir 50 mg (GT 3, Cohort 2)
Participants with GT 3 HCV infection will receive voxilaprevir 50 mg once daily for 3 days under fasted conditions.
Drug: Voxilaprevir
Voxilaprevir tablets administered orally once daily
Other Names:
  • GS-9857
Experimental: Voxilaprevir 100 mg (GT 3, Cohort 2)
Participants with GT 3 HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.
Drug: Voxilaprevir
Voxilaprevir tablets administered orally once daily
Other Names:
  • GS-9857
Experimental: Voxilaprevir 300 mg (GT 3, Cohort 2)
Participants with GT 3 HCV infection will receive voxilaprevir 300 mg once daily for 3 days under fasted conditions.
Drug: Voxilaprevir
Voxilaprevir tablets administered orally once daily
Other Names:
  • GS-9857
Placebo Comparator: Placebo (GT 2, Cohort 3)
Participants with GT 2 HCV infection will receive placebo once daily for 3 days under fasted conditions.
Drug: Placebo to match voxilaprevir
Placebo to match voxilaprevir tablets administered orally once daily
Experimental: Voxilaprevir 100 mg (GT 2, Cohort 3)
Participants with GT 2 HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.
Drug: Voxilaprevir
Voxilaprevir tablets administered orally once daily
Other Names:
  • GS-9857
Experimental: Voxilaprevir 100 mg (GT 4, Cohort 4)
Participants with GT 4 HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.
Drug: Voxilaprevir
Voxilaprevir tablets administered orally once daily
Other Names:
  • GS-9857
Experimental: Voxilaprevir 100 mg (GT 1b, Cohort 5)
Participants with GT 1b HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.
Drug: Voxilaprevir
Voxilaprevir tablets administered orally once daily
Other Names:
  • GS-9857
Experimental: Voxilaprevir 100 mg Fed (GT 3a, Cohort 6)
Participants with GT 3a HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fed conditions.
Drug: Voxilaprevir
Voxilaprevir tablets administered orally once daily
Other Names:
  • GS-9857
Experimental: Voxilaprevir 600 mg (Cohorts 7-9)
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.
Drug: Voxilaprevir
Voxilaprevir tablets administered orally once daily
Other Names:
  • GS-9857
Experimental: Voxilaprevir 100 mg + SOF/VEL 400/100 mg (Group 1, Cohort 10)
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.
Drug: Voxilaprevir
Voxilaprevir tablets administered orally once daily
Other Names:
  • GS-9857
Drug: SOF/VEL
400 mg/100 mg FDC tablet administered orally once daily
Experimental: Voxilaprevir 100 mg + SOF/VEL 400/100 mg (Group 2, Cohort 10)
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.
Drug: Voxilaprevir
Voxilaprevir tablets administered orally once daily
Other Names:
  • GS-9857
Drug: SOF/VEL
400 mg/100 mg FDC tablet administered orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Experiencing Treatment Emergent Adverse Events
Time Frame: First dose date up to Day 3 plus 30 days
First dose date up to Day 3 plus 30 days
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
Time Frame: 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.
First dose date up to Day 3 plus 30 days
Antiviral Activity of Voxilaprevir as Measured by Change From Baseline in Plasma HCV RNA
Time Frame: 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.
Baseline; Days 4, 5, 6, 7, 8, 10, and Week 48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Antiviral Activity of Voxilaprevir as Measured by Absolute HCV RNA Level Through Week 48
Time Frame: 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).
Baseline (Pre Day 1 Dose); Days 4, 5, 6, 7, 8, 10, and Week 48
Antiviral Activity of Voxilaprevir as Measured by Number of Participants Achieving Reductions From Baseline in HCV RNA
Time Frame: 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).
Baseline; Days 4, 5, 6, 7, 8, 10, and Week 48
Percentage of Participants Who Have HCV RNA < Lower Limit of Quantitation (LLOQ) Detected, and < LLOQ Target Not Detected (TND)
Time Frame: 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).
Days 4, 5, 6, 7, 8, 10, and Week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 13, 2014

Primary Completion (Actual)

December 22, 2014

Study Completion (Actual)

September 28, 2015

Study Registration Dates

First Submitted

July 7, 2014

First Submitted That Met QC Criteria

July 7, 2014

First Posted (Estimate)

July 10, 2014

Study Record Updates

Last Update Posted (Actual)

September 17, 2020

Last Update Submitted That Met QC Criteria

August 28, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-338-1121

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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