Clinical trial NCT01701401: 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
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: 2012-10-05
Enrollment: 870
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: 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.


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

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Study Drug (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 Study Drug
timeFrame: Posttreatment Weeks 4 and 24
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: 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: Birmingham
country: United States
state: Alabama
city: La Jolla
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
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: 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: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Wellington
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Decatur
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: Baltimore
country: United States
state: Maryland
city: Lutherville
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Rochester
country: United States
state: Minnesota
city: Saint Paul
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
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: Bronx
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: Chapel Hill
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: Cincinnati
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
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: Falls Church
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: CHRU Lille
country: France
city: Clichy
country: France
city: Creteil
country: France
city: La Tronche
country: France
city: Lyon
country: France
city: Marseille
country: France
city: Nice
country: France
city: Paris
country: France
city: Berlin
country: Germany
city: Dusseldorf
country: Germany
city: Essen
country: Germany
city: Frankfurt
country: Germany
city: Freiburg
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Koln
country: Germany
city: Mainz
country: Germany
city: Bologna
country: Italy
city: Brescia
country: Italy
city: Milan
country: Italy
city: Padova
country: Italy
city: Palermo
country: Italy
city: Roma
country: Italy
city: San Giovanni Rotondo
country: Italy
city: Torino
country: Italy
city: San Juan
country: Puerto Rico
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: Santander
country: Spain
city: Sevilla
country: Spain
city: Birmingham
country: United Kingdom
state: Wstmid
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Plymouth
country: United Kingdom
Study officials:
affiliation: Gilead Sciences
name: Jenny Yang, Pharm D
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: 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.
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.