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

Hepatitis C Virus Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02185794
• Other study ID #: GS-US-338-1121
• Status: Completed
• Phase: Phase 1
• Start date: June 13, 2014
• Est. completion date: September 28, 2015

Study information

• Verified date: August 2020
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: September 28, 2015
• Est. primary completion date: December 22, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus Infection
• Hepatitis C, Chronic
• Infection
• Virus Diseases

Intervention

Drug:
• Voxilaprevir
Voxilaprevir tablets administered orally once daily
• Placebo to match voxilaprevir
Placebo to match voxilaprevir tablets administered orally once daily
• SOF/VEL
400 mg/100 mg FDC tablet administered orally once daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (2)

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):325-3 — View 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 Antivi

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Experiencing Treatment Emergent Adverse Events		First dose date up to Day 3 plus 30 days
Primary	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
Primary	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	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).	Baseline (Pre Day 1 Dose); Days 4, 5, 6, 7, 8, 10, and Week 48
Secondary	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).	Baseline; Days 4, 5, 6, 7, 8, 10, and Week 48
Secondary	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).	Days 4, 5, 6, 7, 8, 10, and Week 48