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Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination ± Ribavirin for the Treatment of HCV (ION-3)

Primary Purpose

Chronic Hepatitis C Virus

Status
Completed
Phase
Phase 3
Locations
United States
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
  • 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
  • Presence of cirrhosis
  • Coinfection 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 subject treatment, assessment or compliance with the protocol

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

LDV/SOF 8 Week

LDV/SOF+RBV 8 Week

LDV/SOF 12 Week

Arm Description

Participants will receive LDV/SOF FDC for 8 weeks.

Participants will receive LDV/SOF FDC plus RBV for 8 weeks.

Participants will receive LDV/SOF FDC for 12 weeks.

Outcomes

Primary Outcome Measures

Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)
SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) 12 weeks following the 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 Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose 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 Experiencing Virologic Failure
Virologic failure was defined as on-treatment virologic failure or virologic relapse. On-Treatment Virologic Failure was defined as Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment) Virologic relapse was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.

Full Information

First Posted
May 3, 2013
Last Updated
October 19, 2018
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT01851330
Brief Title
Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination ± Ribavirin for the Treatment of HCV (ION-3)
Official Title
A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination ± Ribavirin for 8 Weeks and Sofosbuvir/Ledipasvir Fixed-Dose Combination for 12 Weeks in Treatment-Naive Subjects With Chronic Genotype 1 HCV Infection
Study Type
Interventional

2. Study Status

Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
May 2013 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
March 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
This study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) with or without ribavirin (RBV) administered for 8 or 12 weeks in treatment-naive participants 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
647 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LDV/SOF 8 Week
Arm Type
Experimental
Arm Description
Participants will receive LDV/SOF FDC for 8 weeks.
Arm Title
LDV/SOF+RBV 8 Week
Arm Type
Experimental
Arm Description
Participants will receive LDV/SOF FDC plus RBV for 8 weeks.
Arm Title
LDV/SOF 12 Week
Arm Type
Experimental
Arm Description
Participants will receive LDV/SOF FDC for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
LDV/SOF
Other Intervention Name(s)
Harvoni®, GS-5885/GS-7977
Intervention Description
LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
RBV
Intervention Description
Ribavirin (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 12 Weeks After Discontinuation of Therapy (SVR12)
Description
SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) 12 weeks following the 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 12 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
Description
SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose 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 Experiencing Virologic Failure
Description
Virologic failure was defined as on-treatment virologic failure or virologic relapse. On-Treatment Virologic Failure was defined as Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment) Virologic relapse was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.
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 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 Presence of cirrhosis Coinfection 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 subject treatment, assessment or compliance with the protocol
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert H. Hyland, DPhil
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
Country
United States
City
La Jolla
State/Province
California
Country
United States
City
Los Angeles
State/Province
California
Country
United States
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Palo Alto
State/Province
California
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United States
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Sacramento
State/Province
California
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United States
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San Diego
State/Province
California
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United States
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San Francisco
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California
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United States
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Aurora
State/Province
Colorado
Country
United States
City
Englewood
State/Province
Colorado
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United States
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Washington
State/Province
District of Columbia
Country
United States
City
Gainesville
State/Province
Florida
Country
United States
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Jacksonville
State/Province
Florida
Country
United States
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Miami
State/Province
Florida
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United States
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Orlando
State/Province
Florida
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United States
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Wellington
State/Province
Florida
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United States
City
Atlanta
State/Province
Georgia
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United States
City
Decatur
State/Province
Georgia
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United States
City
Marietta
State/Province
Georgia
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United States
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Chicago
State/Province
Illinois
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United States
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Indianapolis
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Indiana
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United States
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Bowling Green
State/Province
Kentucky
Country
United States
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Baton Rouge
State/Province
Louisiana
Country
United States
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Baltimore
State/Province
Maryland
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United States
City
Lutherville
State/Province
Maryland
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United States
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Boston
State/Province
Massachusetts
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United States
City
Novi
State/Province
Michigan
Country
United States
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Kansas City
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Missouri
Country
United States
City
Saint Louis
State/Province
Missouri
Country
United States
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Albuquerque
State/Province
New Jersey
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United States
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Berlin
State/Province
New Jersey
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United States
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Hillsborough
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New Jersey
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United States
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Santa Fe
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New Mexico
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United States
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Binghamton
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New York
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United States
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Manhasset
State/Province
New York
Country
United States
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New York
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New York
Country
United States
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Chapel Hill
State/Province
North Carolina
Country
United States
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Fayetteville
State/Province
North Carolina
Country
United States
City
Statesville
State/Province
North Carolina
Country
United States
City
Winston-Salem
State/Province
North Carolina
Country
United States
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Philadelphia
State/Province
Pennsylvania
Country
United States
City
Providence
State/Province
Rhode Island
Country
United States
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Germantown
State/Province
Tennessee
Country
United States
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Nashville
State/Province
Tennessee
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United States
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Arlington
State/Province
Texas
Country
United States
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Houston
State/Province
Texas
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United States
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San Antonio
State/Province
Texas
Country
United States
City
Fairfax
State/Province
Virginia
Country
United States
City
Falls Church
State/Province
Virginia
Country
United States
City
Newport News
State/Province
Virginia
Country
United States
City
Norfolk
State/Province
Virginia
Country
United States
City
Richmond
State/Province
Virginia
Country
United States
City
Seattle
State/Province
Washington
Country
United States

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
24720702
Citation
Kowdley KV, Gordon SC, Reddy KR, Rossaro L, Bernstein DE, Lawitz E, Shiffman ML, Schiff E, Ghalib R, Ryan M, Rustgi V, Chojkier M, Herring R, Di Bisceglie AM, Pockros PJ, Subramanian GM, An D, Svarovskaia E, Hyland RH, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Pound D, Fried MW; ION-3 Investigators. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014 May 15;370(20):1879-88. doi: 10.1056/NEJMoa1402355. Epub 2014 Apr 10.
Results Reference
derived

Learn more about this trial

Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination ± Ribavirin for the Treatment of HCV (ION-3)

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