Clinical trial NCT02185794: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-07-10
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment Emergent Adverse Events
timeFrame: First dose date up to Day 3 plus 30 days
measure: Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
timeFrame: First dose date up to Day 3 plus 30 days
measure: Antiviral Activity of Voxilaprevir as Measured by Change From Baseline in Plasma HCV RNA
timeFrame: Baseline; Days 4, 5, 6, 7, 8, 10, and Week 48
Secondary outcomes:
measure: Antiviral Activity of Voxilaprevir as Measured by Absolute HCV RNA Level Through Week 48
timeFrame: Baseline (Pre Day 1 Dose); Days 4, 5, 6, 7, 8, 10, and Week 48
measure: Antiviral Activity of Voxilaprevir as Measured by Number of Participants Achieving Reductions From Baseline in HCV RNA
timeFrame: Baseline; Days 4, 5, 6, 7, 8, 10, and Week 48
measure: Percentage of Participants Who Have HCV RNA < Lower Limit of Quantitation (LLOQ) Detected, and < LLOQ Target Not Detected (TND)
timeFrame: Days 4, 5, 6, 7, 8, 10, and Week 48
Other outcomes:
Locations:
city: Costa Mesa
country: United States
state: California
city: DeLand
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Kansas City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Berlin
country: United States
state: New Jersey
city: Marlton
country: United States
state: New Jersey
city: Philadelphia
country: United States
state: Pennsylvania
city: Knoxville
country: United States
state: Tennessee
city: San Antonio
country: United States
state: Texas
city: San Juan
country: Puerto Rico
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
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.
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.