A Phase 3, Open-label Study to Investigate the 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 Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01667731
First received: August 9, 2012
Last updated: March 4, 2014
Last verified: March 2014

August 9, 2012
March 4, 2014
July 2012
November 2013   (final data collection date for primary outcome measure)
  • Proportion of participants with sustained virologic response 12 weeks after discontinuation of treatment (SVR12) [ Time Frame: Posttreatment Week 12 ] [ Designated as safety issue: No ]
    SVR12 is defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
  • Incidence of adverse events leading to permanent discontinuation of study drug(s) [ Time Frame: Baseline up to Week 24 ] [ Designated as safety issue: No ]
  • 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
  • Proportion of participants with sustained virologic response at 4 and 24 weeks after discontinuation of treatment (SVR4 and SVR24) [ Time Frame: Posttreatment Weeks 4 and 24 ] [ Designated as safety issue: No ]
    SVR4 and SVR24 is defined as HCV RNA < the lower limit of quantitation (LLOQ) 4 weeks and 24 weeks following the last dose of study drug, respectively.
  • Proportion of participants with on-treatment virologic failure [ Time Frame: Baseline up to Week 24 ] [ Designated as safety issue: No ]

    Virologic failure is defined as either:

    • Virologic breakthrough (participant achieved undetectable HCV RNA levels during treatment but subsequently had detectable HCV RNA while continuing treatment), or
    • Non-response (HCV RNA persistently ≥ 25 IU/mL through 8 weeks of treatment ), or
    • Virologic relapse (HCV RNA ≥ 25 IU/mL during the posttreatment period having achieved HCV RNA < 25 IU/mL at end of treatment), or
    • Rebound (> 1 log10IU/mLincrease in HCV RNA from nadir while on treatment).
  • HCV RNA change from baseline [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
  • 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
 
A Phase 3, Open-label Study to Investigate the 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 Subjects
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 (GS-7977) plus ribavirin (RBV) in adults with chronic genotypes 1, 2, and 3 HCV infection who are co-infected with HIV-1.

Not Provided
Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hepatitis C,
  • Human Immunodeficiency Virus
  • Drug: Sofosbuvir
    Sofosbuvir 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: Sofosbuvir+RBV 12 weeks TN
    Treatment naive (TN) participants coinfected with HIV-1 and genotypes 2 and 3 HCV infection will receive sofosbuvir plus RBV for 12 weeks.
    Interventions:
    • Drug: Sofosbuvir
    • Drug: RBV
  • Experimental: Sofosbuvir+RBV 24 weeks TE
    Treatment experienced (TE) participants coinfected with HIV-1 and genotypes 2 and 3 HCV infection will receive sofosbuvir plus RBV for 24 weeks.
    Interventions:
    • Drug: Sofosbuvir
    • Drug: RBV
  • Experimental: Sofosbuvir+RBV 24 weeks TN
    Treatment naive (TN) participants coinfected with HIV-1 and genotype 1 HCV infection will receive sofosbuvir plus RBV for 24 weeks.
    Interventions:
    • Drug: Sofosbuvir
    • 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.

*   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:

Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.

  1. Willing and able to provide written informed consent
  2. Male or female, age ≥ 18 years with chronic HCV and HIV-1 infection
  3. HCV RNA > 1 x 104 IU/mL at Screening
  4. Infection with HCV genotype 1, 2 or 3 as determined at Screening
  5. HIV-1 infection confirmed with positive ELISA or Western blot at Screening
  6. The subject's medical records must be sufficient to be categorized on IFN eligibility or prior treatment history with PEG/RBV.
  7. Confirmation of chronic HCV infection
  8. Ability to determine presence/absence of cirrhosis.
  9. HIV antiretroviral therapy (ARV) criteria of one of the following:

    • ARV untreated with a CD4 T-cell count >500 cells/mm3
    • On a stable, protocol-approved, ARV for >8 weeks prior to Screening with a CD4 T-cell count >200 cells/mm3 and a documented undetectable plasma HIV-1 RNA level for ≥ 8 weeks preceding the Screening visit
  10. Approved HIV antiretroviral medications based on drug interaction studies
  11. Subject has not been treated with any investigational drug or device within 30 days of the Screening visit
  12. 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
  13. Male subjects 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
  14. Subject must be of generally good health as determined by the Investigator.
  15. Liver imaging within 6 months of Baseline/Day 1 is required in cirrhotic patients only, to exclude hepatocellular carcinoma (HCC)

Exclusion Criteria:

Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.

  1. Non-genotype 1/2/3 or mixed genotype at Screening
  2. Genotype 1 with prior treatment for HCV
  3. Poor control with ARV regimen
  4. Prior exposure to a direct-acting antiviral targeting the HCV nonstructural protein (NS)5B polymerase
  5. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, α1 antitrypsin deficiency, cholangitis)
  6. A new AIDS-defining condition diagnosed within 30 days prior to screening
  7. Active, serious infection (other than HIV or HCV) requiring parenteral antibiotics, antivirals or antifungals within 30 days prior to Baseline
  8. Infection with hepatitis B virus (HBV)
  9. Contraindication to RBV therapy
  10. Chronic use of systemically administered immunosuppressive agents (e.g., prednisone equivalent > 10 mg/day)
  11. History of solid organ transplantation or malignancy diagnosed or treated within 5 years
  12. 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 Gilead Sciences
Gilead Sciences
March 2014

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