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

Primary Purpose

Chronic Hepatitis C Virus

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Velpatasvir
Placebo
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis C Virus focused on measuring Hepatitis C, HCV, Genotype 1, Genotype 2, Genotype 3, Genotype 4, Genotype 5, Genotype 6, Liver Disease

Eligibility Criteria

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

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.

Sites / Locations

  • West Coast Clinical Trials, LLC
  • Avail Clinical Research, LLC
  • Orlando Clinical Research Center
  • Kansas City Gastroenterology and Hepatology
  • CRI Worldwide, LLC
  • CRI Worldwide, LLC
  • New Orleans Center for Clinical Research-Knoxville
  • Alamo Medical Research
  • Charles River Clinical Services Northwest, Inc.
  • Fundacion De Investigacion De Diego

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 Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Velpatasvir 5 mg (GT 1a)

Velpatasvir 25 mg (GT 1a)

Velpatasvir 50 mg (GT 1a)

Velpatasvir 100 mg (GT 1a)

Velpatasvir 150 mg (GT 1a)

Velpatasvir 150 mg (GT 1b)

Velpatasvir 150 mg (GT 2)

Velpatasvir 25 mg (GT 3)

Velpatasvir 50 mg (GT 3)

Velpatasvir 150 mg (GT 3)

Velpatasvir 150 mg (GT 4)

Velpatasvir up to 400 mg (GT 2)

Arm Description

Participants with genotype (GT) 1a HCV infection will receive velpatasvir 5 mg or placebo once daily for 3 days under fasted conditions.

Participants with GT 1a HCV infection will receive velpatasvir 25 mg or placebo once daily for 3 days under fasted conditions.

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

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

Participants with GT 1a HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.

Participants with GT 1b HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.

Participants with GT 2 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.

Participants with GT 3 HCV infection will receive velpatasvir 25 mg or placebo once daily for 3 days under fasted conditions.

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

Participants with GT 3 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.

Participants with GT 4 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.

Participants with GT 2 HCV infection will receive velpatasvir up to 400 mg or placebo once daily for 3 days under fasted conditions.

Outcomes

Primary Outcome Measures

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).
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.
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.

Secondary Outcome Measures

Absolute HCV RNA Level
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.
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.
Plasma HCV RNA Levels by Treatment and IL28B Genotype
Pharmacokinetic (PK) Parameter of Velpatasvir: AUCinf
AUCinf is defined as the concentration of drug extrapolated to infinite time.
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).
PK Parameter of Velpatasvir: Cmax
Cmax is defined as the maximum observed plasma concentration of drug.
PK Parameter of Velpatasvir: CL/F
CL/F is defined as the apparent oral clearance following administration of the drug.
PK Parameter of Velpatasvir: Ctau
Ctau is defined as the observed drug concentration at the end of the dosing interval.
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.

Full Information

First Posted
November 26, 2012
Last Updated
December 11, 2020
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT01740791
Brief Title
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

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
November 6, 2012 (Actual)
Primary Completion Date
March 15, 2013 (Actual)
Study Completion Date
January 24, 2014 (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
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis C Virus
Keywords
Hepatitis C, HCV, Genotype 1, Genotype 2, Genotype 3, Genotype 4, Genotype 5, Genotype 6, Liver Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
103 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Velpatasvir 5 mg (GT 1a)
Arm Type
Experimental
Arm Description
Participants with genotype (GT) 1a HCV infection will receive velpatasvir 5 mg or placebo once daily for 3 days under fasted conditions.
Arm Title
Velpatasvir 25 mg (GT 1a)
Arm Type
Experimental
Arm Description
Participants with GT 1a HCV infection will receive velpatasvir 25 mg or placebo once daily for 3 days under fasted conditions.
Arm Title
Velpatasvir 50 mg (GT 1a)
Arm Type
Experimental
Arm Description
Participants with GT 1a HCV infection will receive velpatasvir 50 mg or placebo once daily for 3 days under fasted conditions.
Arm Title
Velpatasvir 100 mg (GT 1a)
Arm Type
Experimental
Arm Description
Participants with GT 1a HCV infection will receive velpatasvir 100 mg or placebo once daily for 3 days under fasted conditions.
Arm Title
Velpatasvir 150 mg (GT 1a)
Arm Type
Experimental
Arm Description
Participants with GT 1a HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.
Arm Title
Velpatasvir 150 mg (GT 1b)
Arm Type
Experimental
Arm Description
Participants with GT 1b HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.
Arm Title
Velpatasvir 150 mg (GT 2)
Arm Type
Experimental
Arm Description
Participants with GT 2 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.
Arm Title
Velpatasvir 25 mg (GT 3)
Arm Type
Experimental
Arm Description
Participants with GT 3 HCV infection will receive velpatasvir 25 mg or placebo once daily for 3 days under fasted conditions.
Arm Title
Velpatasvir 50 mg (GT 3)
Arm Type
Experimental
Arm Description
Participants with GT 3 HCV infection will receive velpatasvir 50 mg or placebo once daily for 3 days under fasted conditions.
Arm Title
Velpatasvir 150 mg (GT 3)
Arm Type
Experimental
Arm Description
Participants with GT 3 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.
Arm Title
Velpatasvir 150 mg (GT 4)
Arm Type
Experimental
Arm Description
Participants with GT 4 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.
Arm Title
Velpatasvir up to 400 mg (GT 2)
Arm Type
Experimental
Arm Description
Participants with GT 2 HCV infection will receive velpatasvir up to 400 mg or placebo once daily for 3 days under fasted conditions.
Intervention Type
Drug
Intervention Name(s)
Velpatasvir
Other Intervention Name(s)
GS-5816
Intervention Description
Tablets administered orally
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Tablets administered orally
Primary Outcome Measure Information:
Title
Percentage of Participants Experiencing Treatment Emergent Adverse Events
Description
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).
Time Frame
First dose date up to Day 17 + 2 (Day 19 if Day 17 visit missing)
Title
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
Description
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.
Time Frame
First dose date up to Day 17 + 2 (Day 19 if Day 17 visit missing)
Title
Antiviral Activity of Velpatasvir as Measured by Change in Plasma HCV RNA From Baseline
Description
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.
Time Frame
Baseline; Days 4, 5, 6, 7, 8, 10, and 17
Secondary Outcome Measure Information:
Title
Absolute HCV RNA Level
Time Frame
Baseline; Days 4, 5, 6, 7, 8, 10, and 17
Title
Number of Participants Achieving Reductions From Baseline in HCV RNA
Description
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.
Time Frame
Baseline; Days 4, 5, 6, 7, 8, 10, and 17
Title
Number of Participants Who Have HCV RNA < Lower Limit of Quantitation (LLOQ) Detected
Description
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.
Time Frame
Days 4, 5, 6, 7, and 8
Title
Plasma HCV RNA Levels by Treatment and IL28B Genotype
Time Frame
Days 4, 5, 6, 7, 8, 10, and 17
Title
Pharmacokinetic (PK) Parameter of Velpatasvir: AUCinf
Description
AUCinf is defined as the concentration of drug extrapolated to infinite time.
Time Frame
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
Title
PK Parameter of Velpatasvir: AUCtau
Description
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time Frame
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
Title
PK Parameter of Velpatasvir: Cmax
Description
Cmax is defined as the maximum observed plasma concentration of drug.
Time Frame
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.
Title
PK Parameter of Velpatasvir: CL/F
Description
CL/F is defined as the apparent oral clearance following administration of the drug.
Time Frame
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
Title
PK Parameter of Velpatasvir: Ctau
Description
Ctau is defined as the observed drug concentration at the end of the dosing interval.
Time Frame
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
Title
Number of Participants With Nonstructural Protein 5A (NS5A) Resistance Associated Variants (RAVs) at Pretreatment or Postbaseline Timepoints
Description
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.
Time Frame
First dose date up to Day 17

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
West Coast Clinical Trials, LLC
City
Costa Mesa
State/Province
California
ZIP/Postal Code
92626
Country
United States
Facility Name
Avail Clinical Research, LLC
City
DeLand
State/Province
Florida
ZIP/Postal Code
32720
Country
United States
Facility Name
Orlando Clinical Research Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
Facility Name
Kansas City Gastroenterology and Hepatology
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64131
Country
United States
Facility Name
CRI Worldwide, LLC
City
Marlton
State/Province
New Jersey
ZIP/Postal Code
08053
Country
United States
Facility Name
CRI Worldwide, LLC
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19139
Country
United States
Facility Name
New Orleans Center for Clinical Research-Knoxville
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Facility Name
Alamo Medical Research
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Charles River Clinical Services Northwest, Inc.
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98418
Country
United States
Facility Name
Fundacion De Investigacion De Diego
City
San Juan
ZIP/Postal Code
00927
Country
Puerto Rico

12. IPD Sharing Statement

Citations:
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.
Results Reference
result
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.
Results Reference
result
PubMed Identifier
27353271
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.
Results Reference
derived
PubMed Identifier
26183611
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.
Results Reference
derived

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

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