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

Primary Purpose

Hepatitis C Virus Infection

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Voxilaprevir

Placebo to match voxilaprevir

SOF/VEL

About this trial

This is an interventional treatment trial for Hepatitis C Virus Infection focused on measuring 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

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm Type

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Arm Label

Placebo (GT 1a, Cohort 1)

Voxilaprevir 50 mg (GT 1a, Cohort 1)

Voxilaprevir 100 mg (GT 1a, Cohort 1)

Voxilaprevir 300 mg (GT 1a, Cohort 1)

Placebo (GT 3, Cohort 2)

Voxilaprevir 50 mg (GT 3, Cohort 2)

Voxilaprevir 100 mg (GT 3, Cohort 2)

Voxilaprevir 300 mg (GT 3, Cohort 2)

Placebo (GT 2, Cohort 3)

Voxilaprevir 100 mg (GT 2, Cohort 3)

Voxilaprevir 100 mg (GT 4, Cohort 4)

Voxilaprevir 100 mg (GT 1b, Cohort 5)

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

Voxilaprevir 600 mg (Cohorts 7-9)

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

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

Arm Description

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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.

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.

Outcomes

Primary Outcome Measures

Percentage of Participants Experiencing Treatment Emergent Adverse Events

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.

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.

Secondary Outcome Measures

Antiviral Activity of Voxilaprevir as Measured by Absolute HCV RNA Level Through Week 48

The outcome measure was assessed to evaluate antiviral activity of voxilaprevir only (cohorts 1 through 6).

Antiviral Activity of Voxilaprevir as Measured by Number of Participants Achieving Reductions From Baseline in HCV RNA

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)

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).

Full Information

NCT ID

NCT02185794

First Posted

July 7, 2014

Last Updated

August 28, 2020

Sponsor

Gilead Sciences

1. Study Identification

Unique Protocol Identification Number

NCT02185794

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2020

Overall Recruitment Status

Completed

Study Start Date

June 13, 2014 (Actual)

Primary Completion Date

December 22, 2014 (Actual)

Study Completion Date

September 28, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis C Virus Infection

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

101 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo (GT 1a, Cohort 1)

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Voxilaprevir 50 mg (GT 1a, Cohort 1)

Arm Type

Experimental

Arm Description

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

Arm Title

Voxilaprevir 100 mg (GT 1a, Cohort 1)

Arm Type

Experimental

Arm Description

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

Arm Title

Voxilaprevir 300 mg (GT 1a, Cohort 1)

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo (GT 3, Cohort 2)

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Voxilaprevir 50 mg (GT 3, Cohort 2)

Arm Type

Experimental

Arm Description

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

Arm Title

Voxilaprevir 100 mg (GT 3, Cohort 2)

Arm Type

Experimental

Arm Description

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

Arm Title

Voxilaprevir 300 mg (GT 3, Cohort 2)

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo (GT 2, Cohort 3)

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Voxilaprevir 100 mg (GT 2, Cohort 3)

Arm Type

Experimental

Arm Description

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

Arm Title

Voxilaprevir 100 mg (GT 4, Cohort 4)

Arm Type

Experimental

Arm Description

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

Arm Title

Voxilaprevir 100 mg (GT 1b, Cohort 5)

Arm Type

Experimental

Arm Description

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

Arm Title

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

Arm Type

Experimental

Arm Description

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

Arm Title

Voxilaprevir 600 mg (Cohorts 7-9)

Arm Type

Experimental

Arm Description

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.

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Voxilaprevir

Other Intervention Name(s)

GS-9857

Intervention Description

Voxilaprevir tablets administered orally once daily

Intervention Type

Drug

Intervention Name(s)

Placebo to match voxilaprevir

Intervention Description

Placebo to match voxilaprevir tablets administered orally once daily

Intervention Type

Drug

Intervention Name(s)

SOF/VEL

Intervention Description

400 mg/100 mg FDC tablet administered orally once daily

Primary Outcome Measure Information:

Title

Percentage of Participants Experiencing Treatment Emergent Adverse Events

Time Frame

First dose date up to Day 3 plus 30 days

Title

Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities

Description

Time Frame

First dose date up to Day 3 plus 30 days

Title

Antiviral Activity of Voxilaprevir as Measured by Change From Baseline in Plasma HCV RNA

Description

The outcome measure was assessed to evaluate antiviral activity of voxilaprevir only (cohorts 1 through 6). Data are summarized by treatment/cohort and placebo.

Time Frame

Baseline; Days 4, 5, 6, 7, 8, 10, and Week 48

Secondary Outcome Measure Information:

Title

Antiviral Activity of Voxilaprevir as Measured by Absolute HCV RNA Level Through Week 48

Description

The outcome measure was assessed to evaluate antiviral activity of voxilaprevir only (cohorts 1 through 6).

Time Frame

Baseline (Pre Day 1 Dose); Days 4, 5, 6, 7, 8, 10, and Week 48

Title

Antiviral Activity of Voxilaprevir as Measured by Number of Participants Achieving Reductions From Baseline in HCV RNA

Description

Time Frame

Baseline; Days 4, 5, 6, 7, 8, 10, and Week 48

Title

Percentage of Participants Who Have HCV RNA < Lower Limit of Quantitation (LLOQ) Detected, and < LLOQ Target Not Detected (TND)

Description

Time Frame

Days 4, 5, 6, 7, 8, 10, and Week 48

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gilead Study Director

Organizational Affiliation

Gilead Sciences

Official's Role

Study Director

Facility Information:

City

Costa Mesa

State/Province

California

Country

United States

City

DeLand

State/Province

Florida

Country

United States

City

Orlando

State/Province

Florida

Country

United States

City

Kansas City

State/Province

Missouri

Country

United States

City

Saint Louis

State/Province

Missouri

Country

United States

City

Berlin

State/Province

New Jersey

Country

United States

City

Marlton

State/Province

New Jersey

Country

United States

City

Philadelphia

State/Province

Pennsylvania

Country

United States

City

Knoxville

State/Province

Tennessee

Country

United States

City

San Antonio

State/Province

Texas

Country

United States

City

San Juan

Country

Puerto Rico

12. IPD Sharing Statement

Citations:

Citation

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.

Results Reference

result

PubMed Identifier

29063860

Citation

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.

Results Reference

result

Learn more about this trial

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

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