Clinical trial NCT01667731: Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2 and 3 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) Co-infected Adults
Official title: A Phase 3, Open-label Study to Investigate the Efficacy and Safety of GS-7977 Plus Ribavirin in Chronic Genotype 1, 2 and 3 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) Co-infected Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C
Human Immunodeficiency Virus
Keywords: Hepatitis C
Chronic
HCV
HIV
Human Immunodeficiency Virus
Co-Infected
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2012-08-17
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy, safety, and tolerability of sofosbuvir (SOF; GS-7977) plus ribavirin (RBV) in adults with chronic genotypes 1, 2, and 3 HCV infection who are coinfected with HIV-1.


Eligibility criteria: Inclusion Criteria:

* Willing and able to provide written informed consent
* Male or female, age ≥ 18 years with chronic HCV and HIV-1 infection
* HCV RNA \> 1 x 10\^4 IU/mL at screening
* Infection with HCV genotype 1, 2 or 3 as determined at screening
* HIV-1 infection confirmed with positive ELISA or Western blot at screening
* Medical records must be sufficient to be categorized on interferon (IFN) eligibility or prior treatment history with PEG/RBV.
* Confirmation of chronic HCV infection
* Ability to determine presence/absence of cirrhosis.
* HIV antiretroviral therapy (ARV) criteria of one of the following:

  * ARV untreated with a CD4 T-cell count \> 500 cells/mm\^3
  * On a stable, protocol-approved, ARV for \> 8 weeks prior to screening with a CD4 T-cell count \> 200 cells/mm\^3 and a documented undetectable plasma HIV-1 RNA level for ≥ 8 weeks preceding the screening visit
* Approved HIV antiretroviral medications based on drug interaction studies
* Not been treated with any investigational drug or device within 30 days of the screening visit
* Females if confirmed that she is not pregnant or nursing of non-childbearing potential or of childbearing potential but has a negative serum pregnancy test at screening and agrees to use protocol approved method of birth control from screening through 6 months after the last dose of RBV
* Males who agree to consistently and correctly use a condom while their female partner agrees to use protocol approved method of birth control from screening through 7 months after the last dose of RBV
* Must be of generally good health as determined by the investigator.
* Liver imaging within 6 months of baseline/Day 1 is required in cirrhotic patients only, to exclude hepatocellular carcinoma (HCC)

Exclusion Criteria:

* Non-genotype 1/2/3 or mixed genotype at screening
* Genotype 1 with prior treatment for HCV
* Poor control with ARV regimen
* Prior exposure to a direct-acting antiviral targeting the HCV nonstructural protein (NS)5B polymerase
* Chronic liver disease of a non-HCV etiology (eg, hemochromatosis, Wilson's disease, α1 antitrypsin deficiency, cholangitis)
* A new AIDS-defining condition diagnosed within 30 days prior to screening
* Active, serious infection (other than HIV or HCV) requiring parenteral antibiotics, antivirals or antifungals within 30 days prior to baseline
* Infection with hepatitis B virus (HBV)
* Contraindication to RBV therapy
* Chronic use of systemically administered immunosuppressive agents (eg, prednisone equivalent \> 10 mg/day)
* History of solid organ transplantation or malignancy diagnosed or treated within 5 years
* Current or prior history of clinical hepatic decompensation or other significant gastrointestinal disorder

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)
timeFrame: Posttreatment Week 12
measure: Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
timeFrame: Posttreatment Weeks 4 and 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 6
timeFrame: Baseline; Week 6
measure: Change From Baseline in HCV RNA at Week 8
timeFrame: Baseline; Week 8
measure: Percentage of Participants Experiencing On-treatment Virologic Failure
timeFrame: Up to 24 weeks
measure: Percentage of Participants Experiencing Viral Relapse
timeFrame: Up to Posttreatment Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Coronado
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Lutherville
country: United States
state: California
city: Oakland
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Torrance
country: United States
state: California
city: Washington DC
country: United States
state: District of Columbia
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Springfield
country: United States
state: Massachusetts
city: Kansas City
country: United States
state: Missouri
city: Hillsborough
country: United States
state: New Jersey
city: Santa Fe
country: United States
state: New Mexico
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: 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: Seattle
country: United States
state: Washington
city: San Juan
country: Puerto Rico
Study officials:
affiliation: Gilead Sciences
name: Anuj Gaggar, MD, PhD
role: STUDY_DIRECTOR
References:
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.
citation: Younossi ZM, Stepanova M, Sulkowski M, Naggie S, Puoti M, Orkin C, Hunt SL. Sofosbuvir and Ribavirin for Treatment of Chronic Hepatitis C in Patients Coinfected With Hepatitis C Virus and HIV: The Impact on Patient-Reported Outcomes. J Infect Dis. 2015 Aug 1;212(3):367-77. doi: 10.1093/infdis/jiv005. Epub 2015 Jan 12.
citation: Sulkowski MS, Naggie S, Lalezari J, Fessel WJ, Mounzer K, Shuhart M, Luetkemeyer AF, Asmuth D, Gaggar A, Ni L, Svarovskaia E, Brainard DM, Symonds WT, Subramanian GM, McHutchison JG, Rodriguez-Torres M, Dieterich D; PHOTON-1 Investigators. Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection. JAMA. 2014 Jul 23-30;312(4):353-61. doi: 10.1001/jama.2014.7734.