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

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ClinicalTrials.gov Identifier: NCT02185794
Recruitment Status : Completed
First Posted : July 10, 2014
Results First Posted : August 21, 2020
Last Update Posted : September 17, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Description
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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.

Condition or disease Intervention/treatment Phase
Hepatitis C Virus Infection Drug: Voxilaprevir Drug: Placebo to match voxilaprevir Drug: SOF/VEL Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 101 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 13, 2014
Actual Primary Completion Date : December 22, 2014
Actual Study Completion Date : September 28, 2015

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: GS-9857

Drug: SOF/VEL
400 mg/100 mg FDC tablet administered orally once daily


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants Experiencing Treatment Emergent Adverse Events [ Time Frame: First dose date up to Day 3 plus 30 days ]
  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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).

  3. 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).


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02185794


Locations
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United States, California
Costa Mesa, California, United States
United States, Florida
DeLand, Florida, United States
Orlando, Florida, United States
United States, Missouri
Kansas City, Missouri, United States
Saint Louis, Missouri, United States
United States, New Jersey
Berlin, New Jersey, United States
Marlton, New Jersey, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Tennessee
Knoxville, Tennessee, United States
United States, Texas
San Antonio, Texas, United States
Puerto Rico
San Juan, Puerto Rico
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
More Information
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Publications of Results:
Rodriguez-Torres M, Glass S, Hill J, Freilich B, Hassman D, Di Bisceglie A, Taylor J, Kirby B, Yang J, An D, Stamm L, Brainard D, Kim S, Krefetz D, Smith W, Marbury T, Lawitz E. The Pangenotypic NS3/4A Protease Inhibitor GS-9857 Demonstrates Potent Antiviral Activity in Patients Infected With HCV Genotype 1, 2, 3, or 4 in a 3-Day Monotherapy Study [Poster P0901]. Presented at the European Association for the Study of the Liver (EASL) 50th International Liver Congress 2015, April 22-26, 2015, Vienna, Austria.

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02185794    
Other Study ID Numbers: GS-US-338-1121
First Posted: July 10, 2014    Key Record Dates
Results First Posted: August 21, 2020
Last Update Posted: September 17, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gilead Sciences:
Sustained Virologic Response
Direct Acting Antiviral
Combination Therapy
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
 RNA Virus Infections
Flaviviridae Infections
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Additional relevant MeSH terms:
Layout table for MeSH terms
Infections
Communicable Diseases
Hepatitis A
Virus Diseases
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Disease Attributes
Pathologic Processes
 Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Blood-Borne Infections
Flaviviridae Infections
Hepatitis, Chronic