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Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination (FDC) With and Without Ribavirin for the Treatment of HCV

Primary Purpose

Chronic Hepatitis C Virus

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
LDV/SOF
RBV
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 HCV genotype 1 (GT-1), HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, GS-7977, GS-5885, Ribavirin, Open Label, Sofosbuvir, Additional relevant MeSH terms:, Hepatitis, Hepatitis, Chronic, Hepatitis C, Hepatitis C, Chronic, Liver Diseases, Digestive System Diseases, Hepatitis, Viral, Human, Virus Diseases, Enterovirus Infections, Picornaviridae Infections, RNA Virus Infections, Flaviviridae Infections, Antiviral Agents, Anti-Infective Agents, Therapeutic Uses, Pharmacologic Actions, Antimetabolites, Molecular Mechanisms of Pharmacological Action

Eligibility Criteria

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

Inclusion Criteria:

  • Age ≥ 18, with chronic genotype 1 HCV infection
  • HCV treatment-naive
  • HCV RNA > 10,000 IU/mL at screening
  • Cirrhosis determination; a liver biopsy may be required
  • Screening laboratory values within defined thresholds
  • Use of two effective contraception methods if female of childbearing potential or sexually active male

Exclusion Criteria:

  • Pregnant or nursing female or male with pregnant female partner
  • Co-infection with HIV or hepatitis B virus (HBV)
  • Current or prior history of clinical hepatic decompensation
  • Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers)
  • Chronic use of systemic immunosuppressive agents
  • History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

LDV/SOF 12 weeks

LDV/SOF+RBV 12 weeks

LDV/SOF 24 weeks

LDV/SOF+RBV 24 weeks

Arm Description

LDV/SOF administered for 12 weeks

LDV/SOF+RBV administered for 12 weeks.

LDV/SOF administered for 24 weeks

LDV/SOF+RBV administered for 24 weeks.

Outcomes

Primary Outcome Measures

Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Study Drug (SVR12)
SVR12 was defined as HCV RNA level < the lower limit of quantification (LLOQ, ie, < 25 copies/mL) 12 weeks after last dose of study drug.
Incidence of Adverse Events Leading to Permanent Discontinuation From Any Study Drug
The percentage of participants who experienced an adverse event leading to permanent discontinuation from any study drug was summarized.

Secondary Outcome Measures

Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Study Drug
SVR4 and SVR24 were defined as HCV RNA level < LLOQ at 4 and 24 weeks after discontinuation of study drug, respectively.
Percentage of Participants With HCV RNA < LLOQ at Week 2
Percentage of Participants With HCV RNA < LLOQ at Week 4
Percentage of Participants With HCV RNA < LLOQ at Week 8
Change From Baseline in HCV RNA at Week 2
Change From Baseline in HCV RNA at Week 4
Change From Baseline in HCV RNA at Week 8
Percentage of Participants With Virologic Failure
On-treatment virologic failure was defined as: Breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, confirmed with 2 consecutive values (second confirmation value could have been posttreatment), or last available on-treatment measurement with no subsequent follow- up values, OR Rebound: > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (second confirmation value could have been posttreatment), or last available on-treatment measurement with no subsequent follow-up values, OR Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment Virologic relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement

Full Information

First Posted
October 2, 2012
Last Updated
October 19, 2018
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT01701401
Brief Title
Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination (FDC) With and Without Ribavirin for the Treatment of HCV
Official Title
A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/GS-5885 Fixed-Dose Combination (FDC) +/- Ribavirin for 12 and 24 Weeks in Treatment-Naive Subjects With Chronic Genotype 1 HCV Infection.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir (LDV)/sofosbuvir (SOF) fixed-dose combination (FDC) tablets with or without ribavirin (RBV) administered for 12 and 24 weeks in treatment-naive subjects with chronic genotype 1 HCV infection.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis C Virus
Keywords
HCV genotype 1 (GT-1), HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, GS-7977, GS-5885, Ribavirin, Open Label, Sofosbuvir, Additional relevant MeSH terms:, Hepatitis, Hepatitis, Chronic, Hepatitis C, Hepatitis C, Chronic, Liver Diseases, Digestive System Diseases, Hepatitis, Viral, Human, Virus Diseases, Enterovirus Infections, Picornaviridae Infections, RNA Virus Infections, Flaviviridae Infections, Antiviral Agents, Anti-Infective Agents, Therapeutic Uses, Pharmacologic Actions, Antimetabolites, Molecular Mechanisms of Pharmacological Action

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
870 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LDV/SOF 12 weeks
Arm Type
Experimental
Arm Description
LDV/SOF administered for 12 weeks
Arm Title
LDV/SOF+RBV 12 weeks
Arm Type
Experimental
Arm Description
LDV/SOF+RBV administered for 12 weeks.
Arm Title
LDV/SOF 24 weeks
Arm Type
Experimental
Arm Description
LDV/SOF administered for 24 weeks
Arm Title
LDV/SOF+RBV 24 weeks
Arm Type
Experimental
Arm Description
LDV/SOF+RBV administered for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
LDV/SOF
Other Intervention Name(s)
Harvoni®, GS-5885/GS-7977
Intervention Description
LDV/SOF 90/400 mg FDC tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
RBV
Intervention Description
RBV tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
Primary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Study Drug (SVR12)
Description
SVR12 was defined as HCV RNA level < the lower limit of quantification (LLOQ, ie, < 25 copies/mL) 12 weeks after last dose of study drug.
Time Frame
Posttreatment Week 12
Title
Incidence of Adverse Events Leading to Permanent Discontinuation From Any Study Drug
Description
The percentage of participants who experienced an adverse event leading to permanent discontinuation from any study drug was summarized.
Time Frame
Up to 24 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Study Drug
Description
SVR4 and SVR24 were defined as HCV RNA level < LLOQ at 4 and 24 weeks after discontinuation of study drug, respectively.
Time Frame
Posttreatment Weeks 4 and 24
Title
Percentage of Participants With HCV RNA < LLOQ at Week 2
Time Frame
Week 2
Title
Percentage of Participants With HCV RNA < LLOQ at Week 4
Time Frame
Week 4
Title
Percentage of Participants With HCV RNA < LLOQ at Week 8
Time Frame
Week 8
Title
Change From Baseline in HCV RNA at Week 2
Time Frame
Baseline; Week 2
Title
Change From Baseline in HCV RNA at Week 4
Time Frame
Baseline; Week 4
Title
Change From Baseline in HCV RNA at Week 8
Time Frame
Baseline; Week 8
Title
Percentage of Participants With Virologic Failure
Description
On-treatment virologic failure was defined as: Breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, confirmed with 2 consecutive values (second confirmation value could have been posttreatment), or last available on-treatment measurement with no subsequent follow- up values, OR Rebound: > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (second confirmation value could have been posttreatment), or last available on-treatment measurement with no subsequent follow-up values, OR Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment Virologic relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement
Time Frame
Baseline to posttreatment Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18, with chronic genotype 1 HCV infection HCV treatment-naive HCV RNA > 10,000 IU/mL at screening Cirrhosis determination; a liver biopsy may be required Screening laboratory values within defined thresholds Use of two effective contraception methods if female of childbearing potential or sexually active male Exclusion Criteria: Pregnant or nursing female or male with pregnant female partner Co-infection with HIV or hepatitis B virus (HBV) Current or prior history of clinical hepatic decompensation Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers) Chronic use of systemic immunosuppressive agents History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jenny Yang, Pharm D
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
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United States
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La Jolla
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California
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United States
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Long Beach
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Los Angeles
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Palo Alto
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Sacramento
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San Diego
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Aurora
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Englewood
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Miami
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Orlando
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Tampa
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Wellington
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Atlanta
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Decatur
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Marietta
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Chicago
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Indianapolis
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Lutherville
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Boston
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Detroit
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Rochester
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Saint Paul
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Kansas City
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Saint Louis
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Hillsborough
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Albuquerque
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Santa Fe
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Bronx
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Manhasset
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New York
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New York
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Asheville
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Chapel Hill
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Durham
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Fayetteville
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Statesville
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Winston-Salem
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Cincinnati
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Philadelphia
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Germantown
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Nashville
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Arlington
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Houston
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San Antonio
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Fairfax
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Falls Church
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Norfolk
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Richmond
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Seattle
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CHRU Lille
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France
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Clichy
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France
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Creteil
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France
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La Tronche
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France
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Lyon
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France
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Marseille
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France
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Nice
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France
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Paris
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France
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Berlin
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Germany
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Dusseldorf
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Germany
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Essen
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Germany
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Frankfurt
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Germany
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Freiburg
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Germany
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Hamburg
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Germany
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Hannover
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Germany
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Koln
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Germany
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Mainz
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Germany
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Bologna
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Italy
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Brescia
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Italy
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Milan
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Italy
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Padova
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Italy
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Palermo
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Italy
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Roma
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Italy
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San Giovanni Rotondo
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Italy
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Torino
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San Juan
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Puerto Rico
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Barcelona
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Madrid
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Malaga
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Santander
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Spain
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Sevilla
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Spain
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Birmingham
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Wstmid
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
City
Plymouth
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
IPD Sharing Time Frame
18 months after study completion
IPD Sharing Access Criteria
A secured external environment with username, password, and RSA code.
IPD Sharing URL
http://www.gilead.com/research/disclosure-and-transparency
Citations:
PubMed Identifier
27553375
Citation
Grebely J, Mauss S, Brown A, Bronowicki JP, Puoti M, Wyles D, Natha M, Zhu Y, Yang J, Kreter B, Brainard DM, Yun C, Carr V, Dore GJ. Efficacy and Safety of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic HCV Genotype 1 Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ION Trials. Clin Infect Dis. 2016 Dec 1;63(11):1405-1411. doi: 10.1093/cid/ciw580. Epub 2016 Aug 23.
Results Reference
derived
PubMed Identifier
26280786
Citation
Younossi ZM, Elsheikh E, Stepanova M, Gerber L, Nader F, Stamm LM, Brainard DM, McHutchinson JG. Ledipasvir/sofosbuvir treatment of hepatitis C virus is associated with reduction in serum apolipoprotein levels. J Viral Hepat. 2015 Dec;22(12):977-82. doi: 10.1111/jvh.12448. Epub 2015 Aug 17.
Results Reference
derived
PubMed Identifier
24725239
Citation
Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, Romero-Gomez M, Zarski JP, Agarwal K, Buggisch P, Foster GR, Brau N, Buti M, Jacobson IM, Subramanian GM, Ding X, Mo H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Mangia A, Marcellin P; ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014 May 15;370(20):1889-98. doi: 10.1056/NEJMoa1402454. Epub 2014 Apr 11.
Results Reference
derived

Learn more about this trial

Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination (FDC) With and Without Ribavirin for the Treatment of HCV

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