Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Velpatasvir in Participants With Chronic HCV Infection

Chronic Hepatitis C Virus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01740791
• Other study ID #: GS-US-281-0102
• Status: Completed
• Phase: Phase 1
• Start date: November 6, 2012
• Est. completion date: January 24, 2014

Study information

• Verified date: December 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, tolerability, and antiviral activity of velpatasvir (formerly GS-5816) in HCV treatment naive participants with genotypes 1-6.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: January 24, 2014
• Est. primary completion date: March 15, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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, a1 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.

Related Conditions & MeSH terms

• Chronic Hepatitis C Virus
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Velpatasvir
Tablets administered orally
• Placebo
Tablets administered orally

Locations

Country	Name	City	State
Puerto Rico	Fundacion De Investigacion De Diego	San Juan
United States	West Coast Clinical Trials, LLC	Costa Mesa	California
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	Kansas City Gastroenterology and Hepatology	Kansas City	Missouri
United States	New Orleans Center for Clinical Research-Knoxville	Knoxville	Tennessee
United States	CRI Worldwide, LLC	Marlton	New Jersey
United States	Orlando Clinical Research Center	Orlando	Florida
United States	CRI Worldwide, LLC	Philadelphia	Pennsylvania
United States	Alamo Medical Research	San Antonio	Texas
United States	Charles River Clinical Services Northwest, Inc.	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (2)

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 Varian

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Experiencing Treatment Emergent Adverse Events	Treatment-emergent adverse events were defined as any new or worsening adverse event that began on or after the date of the first dose of study drug until the Day 17 study visit date + 2 (Day 19 if Day 17 visit missing).	First dose date up to Day 17 + 2 (Day 19 if Day 17 visit missing)
Primary	Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities	A treatment-emergent laboratory abnormality was defined as an increase of at least 1 abnormality grade from baseline at any postbaseline visit up to the Day 17 visit date + 2 days (or Day 19 if Day 17 visit was missing). The criteria used to grade laboratory results were as follows: Grade 1 (mild), Grade 2 (moderate), or Grade 3 (severe). Graded laboratory abnormalities were defined using the grading scheme defined in protocol (Gilead Sciences, Inc. Grading Scale for Severity of Adverse Events and Laboratory Abnormalities) for analysis purpose.	First dose date up to Day 17 + 2 (Day 19 if Day 17 visit missing)
Primary	Antiviral Activity of Velpatasvir as Measured by Change in Plasma HCV RNA From Baseline	Participants who were genotyped incorrectly but received appropriate treatment for that genotype were included in that treatment group for the efficacy analysis. Data were summarized by treatment and placebo.	Baseline; Days 4, 5, 6, 7, 8, 10, and 17
Secondary	Absolute HCV RNA Level		Baseline; Days 4, 5, 6, 7, 8, 10, and 17
Secondary	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 by treatment (velpatasvir dose/HCV genotype) and placebo at each collection time point through Day 17.	Baseline; Days 4, 5, 6, 7, 8, 10, and 17
Secondary	Number of Participants Who Have HCV RNA < Lower Limit of Quantitation (LLOQ) Detected	The lower limit of quantitation (LLOQ) detection for HCV RNA levels was 25 IU/mL. HCV detected means calculated HCV RNA level is below LLOQ of the assay.	Days 4, 5, 6, 7, and 8
Secondary	Plasma HCV RNA Levels by Treatment and IL28B Genotype		Days 4, 5, 6, 7, 8, 10, and 17
Secondary	Pharmacokinetic (PK) Parameter of Velpatasvir: AUCinf	AUCinf is defined as the concentration of drug extrapolated to infinite time.	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
Secondary	PK Parameter of Velpatasvir: AUCtau	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).	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
Secondary	PK Parameter of Velpatasvir: Cmax	Cmax is defined as the maximum observed plasma concentration of drug.	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.
Secondary	PK Parameter of Velpatasvir: CL/F	CL/F is defined as the apparent oral clearance following administration of the drug.	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
Secondary	PK Parameter of Velpatasvir: Ctau	Ctau is defined as the observed drug concentration at the end of the dosing interval.	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
Secondary	Number of Participants With Nonstructural Protein 5A (NS5A) Resistance Associated Variants (RAVs) at Pretreatment or Postbaseline Timepoints	The full-length NS5A coding region was analyzed pretreatment (baseline) by deep sequencing using MiSeq for all 70 participants who received velpatasvir and for 8 of 17 participants who received placebo prior to and up to 2 weeks (Day 17) after dosing with velpatasvir. Participants were categorized by velpatasvir dose/HCV genotype and presence or absence of NS5A RAVs.	First dose date up to Day 17