Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 Weeks in Subjects With Chronic Genotype 1 or 4 HCV and HIV-1 Co-infection

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ClinicalTrials.gov Identifier: NCT02073656

Recruitment Status : Completed

First Posted : February 27, 2014

Results First Posted : October 21, 2016

Last Update Posted : November 16, 2018

Sponsor:

Information provided by (Responsible Party):

Gilead Sciences

Study Description

Brief Summary:

This study will evaluate the antiviral efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) administered for 12 weeks in hepatitis C virus (HCV) treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic genotype 1 or 4 HCV infection who are co-infected with HIV-1.

Participants who experience confirmed post-treatment virologic failure (relapse) at or before Posttreatment Week 24 may be eligible to be enrolled in the Retreatment Substudy to receive LDV/SOF plus ribavirin (RBV) for 24 weeks.

Condition or disease	Intervention/treatment	Phase
Hepatitis C Virus HIV	Drug: LDV/SOF Drug: RBV	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	335 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 3, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination for 12 Weeks in Subjects With Chronic Genotype 1 or 4 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV)-1 Co-infection
Study Start Date :	February 2014
Actual Primary Completion Date :	November 2014
Actual Study Completion Date :	December 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS Hepatitis Hepatitis C

Drug Information available for: Sofosbuvir

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: LDV/SOF 12 Weeks LDV/SOF for 12 weeks	Drug: LDV/SOF 90/400 mg FDC tablet administered orally once daily Other Names: Harvoni® GS-5885/GS-7977
Experimental: Retreatment Substudy LDV/SOF plus RBV for 24 weeks	Drug: LDV/SOF 90/400 mg FDC tablet administered orally once daily Other Names: Harvoni® GS-5885/GS-7977 Drug: 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)

Outcome Measures

Primary Outcome Measures :

Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]
SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event [ Time Frame: Up to 12 weeks ]

Secondary Outcome Measures :

Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) [ Time Frame: Posttreatment Weeks 4 and 24 ]
SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 [ Time Frame: Weeks 1, 2, 4, 6, 8, 10, and 12 ]
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, and 8 [ Time Frame: Baseline; Weeks 1, 2, 4, 6, and 8 ]
Percentage of Participants With Virologic Failure [ Time Frame: Up to Posttreatment Week 24 ]
Virologic failure was defined as:
- On-treatment virologic failure:
  - 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:
  - Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.
Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment [ Time Frame: Weeks 4, 8, and 12 ]
Change From Baseline in Serum Creatinine at the End of Treatment (Week 12) and at Posttreatment Weeks 12 and 24 [ Time Frame: Baseline; Week 12, Posttreatment Weeks 12 and 24 ]
For Participants in the Retreatment Substudy, Percentage of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24) [ Time Frame: Posttreatment Weeks 4, 12, and 24 of Retreatment Substudy ]
SVR4, SVR12, and SVR 24 were defined as HCV RNA < LLOQ at 4, 12, and 24 weeks after stopping study treatment, respectively.
For Participants in the Retreatment Substudy, Percentage of Participants With HCV RNA < LLOQ at Retreatment Weeks 2, 4, 8, 12, 16, 20, and 24 [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, and 24 of the Retreatment Substudy ]
For Participants in the Retreatment Substudy, Change From Baseline in HCV RNA at Retreatment Weeks 2, 4, and 8 [ Time Frame: Baseline; Weeks 2, 4, and 8 of Retreatment Substudy ]
For Participants in the Retreatment Substudy, Percentage of Participants With Virologic Failure [ Time Frame: Up to Posttreatment Week 24 of Retreatment Substudy ]
Virologic failure was defined as:
- On-treatment virologic failure:
  - 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:
  - Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HCV RNA ≥ 10,000 IU/mL at screening
HCV genotype 1 or 4
HIV-1 infection
Cirrhosis determination, a fibroscan or liver biopsy may be required
Screening laboratory values within defined thresholds
Use of protocol specified method(s) of contraception if female of childbearing potential or sexually active male

Exclusion Criteria:

Clinically-significant illness (other than HCV or HIV) or any other major medical disorder that may interfere with subject treatment, assessment, or compliance with the protocol
Current or prior history of clinical hepatic decompensation, hepatocellular carcinoma (HCC), or other malignancy (with the exception of certain resolved skin cancers)
Hepatitis B virus (HBV) infection
Pregnant or nursing female
Chronic use of systemically administered immunosuppressive agents

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02073656

Locations

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United States, Alabama

Birmingham, Alabama, United States, 35294-2170
United States, California

Los Angeles, California, United States, 90027

Newport Beach, California, United States, 92663

Palo Alto, California, United States, 94304-5350

Sacramento, California, United States, 95817

San Diego, California, United States, 92103

San Francisco, California, United States, 94110

Torrance, California, United States, 90502
United States, Colorado

Denver, Colorado, United States, 80209
United States, District of Columbia

Washington, District of Columbia, United States, 20815
United States, Florida

Bradenton, Florida, United States, 34209

Miami, Florida, United States, 33136

Orlando, Florida, United States, 32803

Tampa, Florida, United States, 33614
United States, Georgia

Atlanta, Georgia, United States, 30312

Decatur, Georgia, United States, 30033
United States, Illinois

Chicago, Illinois, United States, 60612
United States, Maryland

Lutherville, Maryland, United States, 21093
United States, Massachusetts

Boston, Massachusetts, United States, 02115
United States, Missouri

Kansas City, Missouri, United States, 64111
United States, New Mexico

Santa Fe, New Mexico, United States, 87505
United States, New York

Bronx, New York, United States, 10468

New York, New York, United States, 10065
United States, North Carolina

Chapel Hill, North Carolina, United States, 27599

Durham, North Carolina, United States, 27710
United States, Ohio

Cincinnati, Ohio, United States, 45267-0595
United States, Pennsylvania

Allentown, Pennsylvania, United States, 18102

Philadelphia, Pennsylvania, United States, 19107
United States, Rhode Island

Providence, Rhode Island, United States, 02906
United States, Texas

Dallas, Texas, United States, 75235

Houston, Texas, United States, 77004
United States, Virginia

Annandale, Virginia, United States, 22003

Richmond, Virginia, United States, 23298-0341
United States, Washington

Seattle, Washington, United States, 98104
Canada, British Columbia

Vancouver, British Columbia, Canada, V6Z 1Y6
Canada, Ontario

Ottawa, Ontario, Canada, K1H 8L6

Toronto, Ontario, Canada, M5G 2N2
Canada, Quebec

Montreal, Quebec, Canada, H2L 5B1
New Zealand

Auckland, New Zealand, 1142

Christchurch, New Zealand, 8011
Puerto Rico

San Juan, Puerto Rico, 00936-5607

Sponsors and Collaborators

Gilead Sciences

Investigators

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Study Director:	Jenny Yang, PharmD	Gilead Sciences

More Information

Publications of Results:

Cooper C, Naggie S, Saag M, Yang JC, Stamm LM, Dvory-Sobol H, et al. Retreatment of Patients Who Failed 12 Weeks of Ledipasvir/Sofosbuvir-Based Regimens with Ledipasvir/Sofosbuvir with Ribavirin for 24 Weeks [Poster Presentation]. 23nd Conference on Retroviruses and Opportunistic Infections (CROI); 2016 February 22-25; Boston, MA.

Naggie S, Cooper C, Saag M, Workowski K, Ruane P, Towner WJ, Marks K, Luetkemeyer A, Baden RP, Sax PE, Gane E, Santana-Bagur J, Stamm LM, Yang JC, German P, Dvory-Sobol H, Ni L, Pang PS, McHutchison JG, Stedman CA, Morales-Ramirez JO, Bräu N, Jayaweera D, Colson AE, Tebas P, Wong DK, Dieterich D, Sulkowski M; ION-4 Investigators. Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med. 2015 Aug 20;373(8):705-13. doi: 10.1056/NEJMoa1501315. Epub 2015 Jul 21.

Naggie S, Cooper C, Saag M, Stamm LM, Yang JC, Pang PS, et al. Ledipasvir/Sofosbuvir for 12 Weeks in Patients Coinfected With HCV and HIV-1 [Oral Presentation]. 22nd Conference on Retroviruses and Opportunistic Infections (CROI); 2015 February 23-26; Seattle, WA.

Cooper C, Naggie S, Saag M, Yang JC, Stamm LM, Dvory-Sobol H, Han L, Pang PS, McHutchison JG, Dieterich D, Sulkowski M. Successful Re-treatment of Hepatitis C Virus in Patients Coinfected With HIV Who Relapsed After 12 Weeks of Ledipasvir/Sofosbuvir. Clin Infect Dis. 2016 Aug 15;63(4):528-31. doi: 10.1093/cid/ciw349. Epub 2016 May 25.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Saeed S, Strumpf EC, Walmsley SL, Rollet-Kurhajec K, Pick N, Martel-Laferrière V, Hull M, Gill MJ, Cox J, Cooper C, Klein MB; Canadian Co-Infection Cohort Study, Cohen J, Conway B, Cooper C, Côté P, Cox J, Gill J, Haider S, Harris M, Haase D, Hull M, Montaner J, Moodie E, Pick N, Rachlis A, Rouleau D, Sandre R, Tyndall JM, Vachon ML, Walmsley S, Wong D. How Generalizable Are the Results From Trials of Direct Antiviral Agents to People Coinfected With HIV/HCV in the Real World? Clin Infect Dis. 2016 Apr 1;62(7):919-926. doi: 10.1093/cid/civ1222. Epub 2016 Jan 6.

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Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT02073656
Other Study ID Numbers:	GS-US-337-0115
First Posted:	February 27, 2014 Key Record Dates
Results First Posted:	October 21, 2016
Last Update Posted:	November 16, 2018
Last Verified:	August 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
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.
Supporting Materials:	Study Protocol Statistical Analysis Plan (SAP)
Time Frame:	18 months after study completion
Access Criteria:	A secured external environment with username, password, and RSA code.
URL:	http://www.gilead.com/research/disclosure-and-transparency

Keywords provided by Gilead Sciences:


genotype 1 genotype 4 HIV

Additional relevant MeSH terms:

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Hepatitis C Coinfection Hepatitis Infections Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases RNA Virus Infections	Blood-Borne Infections Communicable Diseases Flaviviridae Infections Sofosbuvir Ledipasvir, sofosbuvir drug combination Ledipasvir Antiviral Agents Anti-Infective Agents

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