Clinical trial NCT02073656: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C Virus
HIV
Keywords: genotype 1
genotype 4
HIV
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-02-27
Enrollment: 335
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
timeFrame: Posttreatment Week 12
measure: Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
timeFrame: Up to 12 weeks
Secondary outcomes:
measure: Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
timeFrame: Posttreatment Weeks 4 and 24
measure: Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12
timeFrame: Weeks 1, 2, 4, 6, 8, 10, and 12
measure: Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, and 8
timeFrame: Baseline; Weeks 1, 2, 4, 6, and 8
measure: Percentage of Participants With Virologic Failure
timeFrame: Up to Posttreatment Week 24
measure: Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment
timeFrame: Weeks 4, 8, and 12
measure: Change From Baseline in Serum Creatinine at the End of Treatment (Week 12) and at Posttreatment Weeks 12 and 24
timeFrame: Baseline; Week 12, Posttreatment Weeks 12 and 24
measure: 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)
timeFrame: Posttreatment Weeks 4, 12, and 24 of Retreatment Substudy
measure: For Participants in the Retreatment Substudy, Percentage of Participants With HCV RNA < LLOQ at Retreatment Weeks 2, 4, 8, 12, 16, 20, and 24
timeFrame: Weeks 2, 4, 8, 12, 16, 20, and 24 of the Retreatment Substudy
measure: For Participants in the Retreatment Substudy, Change From Baseline in HCV RNA at Retreatment Weeks 2, 4, and 8
timeFrame: Baseline; Weeks 2, 4, and 8 of Retreatment Substudy
measure: For Participants in the Retreatment Substudy, Percentage of Participants With Virologic Failure
timeFrame: Up to Posttreatment Week 24 of Retreatment Substudy
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Los Angeles
country: United States
state: California
city: Newport Beach
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Torrance
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Bradenton
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Decatur
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Lutherville
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Kansas City
country: United States
state: Missouri
city: Santa Fe
country: United States
state: New Mexico
city: Bronx
country: United States
state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Allentown
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Providence
country: United States
state: Rhode Island
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Annandale
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Vancouver
country: Canada
state: British Columbia
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: San Juan
country: Puerto Rico
Study officials:
affiliation: Gilead Sciences
name: Jenny Yang, PharmD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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, Brau 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.
citation: 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.
citation: 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.
citation: Saeed S, Strumpf EC, Walmsley SL, Rollet-Kurhajec K, Pick N, Martel-Laferriere V, Hull M, Gill MJ, Cox J, Cooper C, Klein MB; Canadian Co-Infection Cohort Study; Cohen J, Conway B, Cooper C, Cote 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.