Clinical trial NCT01768286: Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination ± Ribavirin in Treatment-Experienced Subjects With Genotype 1 HCV Infection
Official title: A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/GS-5885 Fixed-Dose Combination ± Ribavirin for 12 and 24 Weeks in Treatment-Experienced Subjects With Chronic Genotype 1 HCV Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: 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
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2013-01-15
Enrollment: 441
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir/sofosbuvir fixed dose combination (FDC) with or without ribavirin (RBV) administered for 12 or 24 weeks in treatment-experienced subjects with chronic genotype 1 hepatitis C virus (HCV) infection.


Eligibility criteria: Inclusion Criteria:

* Age \> 18, with chronic genotype 1 HCV infection
* HCV treatment-experienced, including patients who have previously failed a nonstructural protein (NS)3/4A protease inhibitor plus pegylated interferon (PEG)/RBV regimen
* 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
* Coinfection with HIV or hepatitis B virus
* Current or prior history of clinical hepatic decompensation
* Hepatocellular carcinoma 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

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
timeFrame: Posttreatment Week 12
measure: Incidence of Adverse Events Leading to Permanent Discontinuation From Any Study Drug
timeFrame: Up to 24 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 Week 1
timeFrame: Week 1
measure: Percentage of Participants With HCV RNA < LLOQ at Week 2
timeFrame: Week 2
measure: Percentage of Participants With HCV RNA < LLOQ at Week 4
timeFrame: Week 4
measure: Percentage of Participants With HCV RNA < LLOQ at Week 8
timeFrame: Week 8
measure: Percentage of Participants With HCV RNA < LLOQ at Week 12
timeFrame: Week 12
measure: Percentage of Participants With HCV RNA < LLOQ at Week 24
timeFrame: Week 24
measure: Change From Baseline in HCV RNA at Week 1
timeFrame: Baseline; Week 1
measure: Change From Baseline in HCV RNA at Week 2
timeFrame: Baseline; Week 2
measure: Change From Baseline in HCV RNA at Week 4
timeFrame: Baseline; Week 4
measure: Change From Baseline in HCV RNA at Week 8
timeFrame: Baseline; Week 8
measure: Percentage of Participants With Virologic Failure
timeFrame: Baseline to posttreatment Week 24
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Englewood
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Gainesville
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Bowling Green
country: United States
state: Kentucky
city: Baton Rouge
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Lutherville
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Springfield
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Rochester
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Minnesota
city: Saint Paul
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: Berlin
country: United States
state: New Jersey
city: Hillsborough
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Santa Fe
country: United States
state: New Mexico
city: Binghamton
country: United States
state: New York
city: Manhasset
country: United States
state: New York
city: New York
country: United States
state: New York
city: Asheville
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Fayetteville
country: United States
state: North Carolina
city: Statesville
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Providence
country: United States
state: Rhode Island
city: Germantown
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Fairfax
country: United States
state: Virginia
city: Newport News
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
Study officials:
affiliation: Gilead Sciences
name: Jenny Yang, PharmD
role: STUDY_DIRECTOR
References:
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.
citation: Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, Nahass R, Ghalib R, Gitlin N, Herring R, Lalezari J, Younes ZH, Pockros PJ, Di Bisceglie AM, Arora S, Subramanian GM, Zhu Y, Dvory-Sobol H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Sulkowski M, Kwo P; ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014 Apr 17;370(16):1483-93. doi: 10.1056/NEJMoa1316366. Epub 2014 Apr 11.