Clinical trial NCT01740791: Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Velpatasvir in Participants With Chronic HCV Infection
Official title: Phase 1b, Randomized, Double-Blind, Multiple-Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of GS-5816 in Subjects With Chronic Hepatitis C Virus Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Hepatitis C Virus
Keywords: Hepatitis C
HCV
Genotype 1
Genotype 2
Genotype 3
Genotype 4
Genotype 5
Genotype 6
Liver Disease
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2012-12-04
Enrollment: 103
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, tolerability, and antiviral activity of velpatasvir (formerly GS-5816) in HCV treatment naive participants with genotypes 1-6.


Eligibility criteria: Key Inclusion Criteria:

* HCV treatment-naive adult participants (18-65 years of age) with chronic HCV infection and plasma HCV RNA ≥ 5 log10 IU/mL at screening
* Agree to use protocol defined precautions against pregnancy

Key Exclusion Criteria:

* Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, α1 antitrypsin deficiency, cholangitis)
* Evidence of cirrhosis
* Evidence of current drug abuse
* Screening laboratory results outside the protocol specified requirements

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 17 + 2 (Day 19 if Day 17 visit missing)
measure: Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
timeFrame: First dose date up to Day 17 + 2 (Day 19 if Day 17 visit missing)
measure: Antiviral Activity of Velpatasvir as Measured by Change in Plasma HCV RNA From Baseline
timeFrame: Baseline; Days 4, 5, 6, 7, 8, 10, and 17
Secondary outcomes:
measure: Absolute HCV RNA Level
timeFrame: Baseline; Days 4, 5, 6, 7, 8, 10, and 17
measure: Number of Participants Achieving Reductions From Baseline in HCV RNA
timeFrame: Baseline; Days 4, 5, 6, 7, 8, 10, and 17
measure: Number of Participants Who Have HCV RNA < Lower Limit of Quantitation (LLOQ) Detected
timeFrame: Days 4, 5, 6, 7, and 8
measure: Plasma HCV RNA Levels by Treatment and IL28B Genotype
timeFrame: Days 4, 5, 6, 7, 8, 10, and 17
measure: Pharmacokinetic (PK) Parameter of Velpatasvir: AUCinf
timeFrame: 0 (predose), 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose at Day 1
measure: PK Parameter of Velpatasvir: AUCtau
timeFrame: 0 (predose), 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose at Day 3
measure: PK Parameter of Velpatasvir: Cmax
timeFrame: 0 (predose), 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose at Day 1 for single dose and Day 3 for multiple dose.
measure: PK Parameter of Velpatasvir: CL/F
timeFrame: 0 (predose), 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose at Day 1 for single dose and Day 3 for multiple dose
measure: PK Parameter of Velpatasvir: Ctau
timeFrame: 0 (predose), 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose at Day 3
measure: Number of Participants With Nonstructural Protein 5A (NS5A) Resistance Associated Variants (RAVs) at Pretreatment or Postbaseline Timepoints
timeFrame: First dose date up to Day 17
Other outcomes:
Locations:
city: Costa Mesa
country: United States
facility: West Coast Clinical Trials, LLC
state: California
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Kansas City
country: United States
facility: Kansas City Gastroenterology and Hepatology
state: Missouri
city: Marlton
country: United States
facility: CRI Worldwide, LLC
state: New Jersey
city: Philadelphia
country: United States
facility: CRI Worldwide, LLC
state: Pennsylvania
city: Knoxville
country: United States
facility: New Orleans Center for Clinical Research-Knoxville
state: Tennessee
city: San Antonio
country: United States
facility: Alamo Medical Research
state: Texas
city: Tacoma
country: United States
facility: Charles River Clinical Services Northwest, Inc.
state: Washington
city: San Juan
country: Puerto Rico
facility: Fundacion De Investigacion De Diego
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Hebner C, Gontcharova V, Chodavarapu RK, Rodriguez-Torres M, Lawitz E, Yang C, et al. Deep Sequencing of HCV NS5A From a 3-Day Study of GS-5816 Monotherapy Confirms the Potency of GS-5816 Against Pre-Existing Genotype 1-3 NS5A Resistance-Associated Variants [Abstract 470]. The Liver Meeting The 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2013 November 1-5; Washington, D.C.
citation: Lawitz E, Glass SJ, Gruener D, Freilich B, Hill JM, Link JO, et al. GS-5816, a Once-Daily NS5A Inhibitor, Demonstrates Potent Antiviral Activity in Patients with Genotype 1, 2, 3, or 4 HCV Infection in a 3-Day Monotherapy Study [Abstract 1082]. The Liver Meeting The 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2013 November 1-5; Washington, D.C.
citation: Lawitz EJ, Dvory-Sobol H, Doehle BP, Worth AS, McNally J, Brainard DM, Link JO, Miller MD, Mo H. Clinical Resistance to Velpatasvir (GS-5816), a Novel Pan-Genotypic Inhibitor of the Hepatitis C Virus NS5A Protein. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5368-78. doi: 10.1128/AAC.00763-16. Print 2016 Sep.
citation: Lawitz E, Freilich B, Link J, German P, Mo H, Han L, Brainard DM, McNally J, Marbury T, Rodriguez-Torres M. A phase 1, randomized, dose-ranging study of GS-5816, a once-daily NS5A inhibitor, in patients with genotype 1-4 hepatitis C virus. J Viral Hepat. 2015 Dec;22(12):1011-9. doi: 10.1111/jvh.12435. Epub 2015 Jul 16.