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
  Purpose

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.


Condition Intervention Phase
Hepatitis C,
Human Immunodeficiency Virus
Drug: Sofosbuvir
Drug: RBV
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 224
Study Start Date: July 2012
Study Completion Date: February 2014
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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 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.
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 24 weeks TN
Treatment naive (TN) participants coinfected with HIV-1 and genotype 1 HCV infection will receive sofosbuvir plus RBV for 24 weeks.
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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01667731

  Show 27 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Anuj Gaggar Gilead Sciences
  More Information

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01667731     History of Changes
Other Study ID Numbers: GS-US-334-0123
Study First Received: August 9, 2012
Last Updated: March 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Hepatitis C
Chronic
HCV
HIV
Human Immunodeficiency Virus
Co-Infected

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Hepatitis
Hepatitis A
Hepatitis C
HIV Infections
Immunologic Deficiency Syndromes
Virus Diseases
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Immune System Diseases
Lentivirus Infections
Liver Diseases
Picornaviridae Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 28, 2014