NCT02185794

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
101

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jun 2014

Geographic Reach
2 countries

11 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 13, 2014

Completed
24 days until next milestone

First Submitted

Initial submission to the registry

July 7, 2014

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 10, 2014

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 22, 2014

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 28, 2015

Completed
4.9 years until next milestone

Results Posted

Study results publicly available

August 21, 2020

Completed
Last Updated

September 17, 2020

Status Verified

August 1, 2020

Enrollment Period

6 months

First QC Date

July 7, 2014

Results QC Date

August 6, 2020

Last Update Submit

August 28, 2020

Conditions

Keywords

Sustained Virologic ResponseDirect Acting AntiviralCombination TherapyLiver DiseasesDigestive System DiseasesHepatitis, Viral, HumanEnterovirus InfectionsPicornaviridae InfectionsRNA Virus InfectionsFlaviviridae InfectionsAntiviral AgentsAnti-Infective AgentsTherapeutic UsesPharmacologic ActionsAntimetabolitesMolecular Mechanisms of Pharmacological Action

Outcome Measures

Primary Outcomes (3)

  • 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

    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

    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 Outcomes (3)

  • 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

  • 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

  • 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

Study Arms (16)

Placebo (GT 1a, Cohort 1)

PLACEBO COMPARATOR

Participants with genotype (GT) 1a HCV infection will receive placebo once daily for 3 days under fasted conditions.

Drug: Placebo to match voxilaprevir

Voxilaprevir 50 mg (GT 1a, Cohort 1)

EXPERIMENTAL

Participants with GT 1a HCV infection will receive voxilaprevir 50 mg once daily for 3 days under fasted conditions.

Drug: Voxilaprevir

Voxilaprevir 100 mg (GT 1a, Cohort 1)

EXPERIMENTAL

Participants with GT 1a HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.

Drug: Voxilaprevir

Voxilaprevir 300 mg (GT 1a, Cohort 1)

EXPERIMENTAL

Participants with GT 1a HCV infection will receive voxilaprevir 300 mg once daily for 3 days under fasted conditions.

Drug: Voxilaprevir

Placebo (GT 3, Cohort 2)

PLACEBO COMPARATOR

Participants with GT 3 HCV infection will receive placebo once daily for 3 days under fasted conditions.

Drug: Placebo to match voxilaprevir

Voxilaprevir 50 mg (GT 3, Cohort 2)

EXPERIMENTAL

Participants with GT 3 HCV infection will receive voxilaprevir 50 mg once daily for 3 days under fasted conditions.

Drug: Voxilaprevir

Voxilaprevir 100 mg (GT 3, Cohort 2)

EXPERIMENTAL

Participants with GT 3 HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.

Drug: Voxilaprevir

Voxilaprevir 300 mg (GT 3, Cohort 2)

EXPERIMENTAL

Participants with GT 3 HCV infection will receive voxilaprevir 300 mg once daily for 3 days under fasted conditions.

Drug: Voxilaprevir

Placebo (GT 2, Cohort 3)

PLACEBO COMPARATOR

Participants with GT 2 HCV infection will receive placebo once daily for 3 days under fasted conditions.

Drug: Placebo to match voxilaprevir

Voxilaprevir 100 mg (GT 2, Cohort 3)

EXPERIMENTAL

Participants with GT 2 HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.

Drug: Voxilaprevir

Voxilaprevir 100 mg (GT 4, Cohort 4)

EXPERIMENTAL

Participants with GT 4 HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.

Drug: Voxilaprevir

Voxilaprevir 100 mg (GT 1b, Cohort 5)

EXPERIMENTAL

Participants with GT 1b HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.

Drug: Voxilaprevir

Voxilaprevir 100 mg Fed (GT 3a, Cohort 6)

EXPERIMENTAL

Participants with GT 3a HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fed conditions.

Drug: Voxilaprevir

Voxilaprevir 600 mg (Cohorts 7-9)

EXPERIMENTAL

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 100 mg + SOF/VEL 400/100 mg (Group 1, Cohort 10)

EXPERIMENTAL

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: VoxilaprevirDrug: SOF/VEL

Voxilaprevir 100 mg + SOF/VEL 400/100 mg (Group 2, Cohort 10)

EXPERIMENTAL

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: VoxilaprevirDrug: SOF/VEL

Interventions

Voxilaprevir tablets administered orally once daily

Also known as: GS-9857
Voxilaprevir 100 mg (GT 1a, Cohort 1)Voxilaprevir 100 mg (GT 1b, Cohort 5)Voxilaprevir 100 mg (GT 2, Cohort 3)Voxilaprevir 100 mg (GT 3, Cohort 2)Voxilaprevir 100 mg (GT 4, Cohort 4)Voxilaprevir 100 mg + SOF/VEL 400/100 mg (Group 1, Cohort 10)Voxilaprevir 100 mg + SOF/VEL 400/100 mg (Group 2, Cohort 10)Voxilaprevir 100 mg Fed (GT 3a, Cohort 6)Voxilaprevir 300 mg (GT 1a, Cohort 1)Voxilaprevir 300 mg (GT 3, Cohort 2)Voxilaprevir 50 mg (GT 1a, Cohort 1)Voxilaprevir 50 mg (GT 3, Cohort 2)Voxilaprevir 600 mg (Cohorts 7-9)

Placebo to match voxilaprevir tablets administered orally once daily

Placebo (GT 1a, Cohort 1)Placebo (GT 2, Cohort 3)Placebo (GT 3, Cohort 2)

400 mg/100 mg FDC tablet administered orally once daily

Voxilaprevir 100 mg + SOF/VEL 400/100 mg (Group 1, Cohort 10)Voxilaprevir 100 mg + SOF/VEL 400/100 mg (Group 2, Cohort 10)

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Unknown Facility

Costa Mesa, California, United States

Location

Unknown Facility

DeLand, Florida, United States

Location

Unknown Facility

Orlando, Florida, United States

Location

Unknown Facility

Kansas City, Missouri, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Berlin, New Jersey, United States

Location

Unknown Facility

Marlton, New Jersey, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Knoxville, Tennessee, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

Unknown Facility

San Juan, Puerto Rico

Location

Related Publications (2)

  • 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.

    RESULT
  • Lawitz E, Yang JC, Stamm LM, Taylor JG, Cheng G, Brainard DM, Miller MD, Mo H, Dvory-Sobol H. Characterization of HCV resistance from a 3-day monotherapy study of voxilaprevir, a novel pangenotypic NS3/4A protease inhibitor. Antivir Ther. 2018;23(4):325-334. doi: 10.3851/IMP3202.

MeSH Terms

Conditions

Hepatitis CLiver DiseasesDigestive System DiseasesHepatitis, Viral, HumanEnterovirus InfectionsPicornaviridae InfectionsRNA Virus InfectionsFlaviviridae Infections

Interventions

voxilaprevir

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsVirus DiseasesHepatitis

Results Point of Contact

Title
Gilead Clinical Study Information Center
Organization
Gilead Sciences

Study Officials

  • Gilead Study Director

    Gilead Sciences

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 7, 2014

First Posted

July 10, 2014

Study Start

June 13, 2014

Primary Completion

December 22, 2014

Study Completion

September 28, 2015

Last Updated

September 17, 2020

Results First Posted

August 21, 2020

Record last verified: 2020-08

Locations