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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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01667731
First received: August 9, 2012
Last updated: November 14, 2014
Last verified: November 2014

August 9, 2012
November 14, 2014
July 2012
November 2013   (final data collection date for primary outcome measure)
  • Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ] [ Designated as safety issue: No ]
    SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
  • Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
    The percentage of participants discontinuing any study drug due to an adverse event was summarized.
  • Efficacy of GS-7977 + Ribavirin (RBV) [ Time Frame: 12 or 24 weeks + 12 wk follow up ] [ Designated as safety issue: No ]
    To determine the efficacy of treatment with GS-7977 + ribavirin (RBV) by proportion of subjects with sustained viral response 12 or 24 weeks (SVR 12 or 24) after discontinuation of therapy
  • Safety and Tolerability of GS-7977 + Ribavirin (RBV) measured by review of accumulated safety data. [ Time Frame: 12 or 24 wk + 30 days ] [ Designated as safety issue: Yes ]
    To evaluate the safety and tolerability of GS-7977 + Ribavirin(RBV) as assessed by review of the accumulated safety data
Complete list of historical versions of study NCT01667731 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) [ Time Frame: Posttreatment Weeks 4 and 24 ] [ Designated as safety issue: No ]
    SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
  • Change From Baseline in HCV RNA at Week 1 [ Time Frame: Baseline; Week 1 ] [ Designated as safety issue: No ]
  • Change From Baseline in HCV RNA at Week 2 [ Time Frame: Baseline; Week 2 ] [ Designated as safety issue: No ]
  • Change From Baseline in HCV RNA at Week 4 [ Time Frame: Baseline; Week 4 ] [ Designated as safety issue: No ]
  • Change From Baseline in HCV RNA at Week 6 [ Time Frame: Baseline; Week 6 ] [ Designated as safety issue: No ]
  • Change From Baseline in HCV RNA at Week 8 [ Time Frame: Baseline; Week 8 ] [ Designated as safety issue: No ]
  • Percentage of Participants Experiencing On-treatment Virologic Failure [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]

    On-treatment virologic failure was defined as:

    1. Viral breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values, or
    2. Viral rebound: > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values, or
    3. Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment
  • Percentage of Participants Experiencing Viral Relapse [ Time Frame: Up to Posttreatment Week 24 ] [ Designated as safety issue: No ]
    Viral relapse was defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) at end of treatment, but did not achieve an SVR.
  • Sustained Viral Response at 4 weeks and 24 weeks (SVR4 and SVR 24) [ Time Frame: 12 or 24 weeks + 4 or 24 wk follow up ] [ Designated as safety issue: No ]
    To determine the proportion of subjects who attain sustained viral response (SVR) at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24)
  • Kinetics of Plasma Ribonucleic Acid (RNA) in Hepatitis C Virus (HCV) [ Time Frame: 12 or 24 weeks ] [ Designated as safety issue: No ]
    To evaluate the kinetics of plasma Ribonucleic Acid (RNA) in Hepatitis C Virus (HCV)during treatment and after treatment discontinuation
  • Emergence of Viral Resistance measured by patients with viral resistance. [ Time Frame: 12 or 24 weeks + 24 wk follow up ] [ Designated as safety issue: No ]
    To evaluate the emergence of viral resistance to GS-7977 during treatment and after treatment discontinuation
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hepatitis C
  • Human Immunodeficiency Virus
  • Drug: SOF
    Sofosbuvir (SOF) 400 mg tablet administered orally once daily
    Other Names:
    • GS-7977
    • PSI-7977
    • Sovaldi®
  • Drug: RBV
    Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg)
  • Experimental: SOF+RBV 12 Weeks (GT 2/3, TN)
    Treatment-naive (TN) participants coinfected with HIV-1 and genotype (GT) 2 or genotype 3 HCV infection will receive SOF+RBV for 12 weeks.
    Interventions:
    • Drug: SOF
    • Drug: RBV
  • Experimental: SOF+RBV 24 Weeks (GT 2/3, TE)
    Treatment-experienced (TE) participants coinfected with HIV-1 and genotype 2 or genotype 3 HCV infection will receive SOF+RBV for 24 weeks.
    Interventions:
    • Drug: SOF
    • Drug: RBV
  • Experimental: SOF+RBV 24 Weeks (GT 1, TN)
    Treatment-naive (TN) participants coinfected with HIV-1 and genotype 1 HCV infection will receive SOF+RBV for 24 weeks.
    Interventions:
    • Drug: SOF
    • Drug: RBV
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. Erratum in: JAMA. 2014 Nov 12;312(18):1932.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
224
February 2014
November 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Puerto Rico
 
NCT01667731
GS-US-334-0123
Yes
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Anuj Gaggar, MD, PhD Gilead Sciences
Gilead Sciences
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP