Part A: Drug Interaction Study of Sofosbuvir and Antiretroviral Therapy (ART) Combinations in HIV and Hepatitis C Virus (HCV) Co-infected Patients. Part B: Efficacy and Safety of Sofosbuvir for 12 Weeks in HIV/HCV Co-infected Patients.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01565889
First received: March 27, 2012
Last updated: December 20, 2013
Last verified: December 2013
  Purpose

This study consists of 2 parts, Part A and Part B. Part A, the Phase 1 drug interaction/early viral kinetic study, will evaluate the effect of selected antiretroviral therapies on the safety, viral kinetics, and pharmacokinetics of sofosbuvir (GS-7977; PSI-7977) and its metabolites in participants with HIV and hepatitis C virus (HCV) coinfection . Part B, the Phase 2 treatment study, will investigate the efficacy and safety of sofosbuvir, peginterferon alfa 2a (PEG) and Ribavirin (RBV) in participants with HIV/HCV coinfection.


Condition Intervention Phase
Hepatitis C
HIV
Drug: Sofosbuvir
Drug: EFV/FTC/TDF
Drug: EFV
Drug: ZDV/3TC
Drug: ATV
Drug: Ritonavir
Drug: FTC/TDF
Drug: DRV
Drug: RAL
Drug: PEG
Drug: RBV
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Part A: Drug Interaction Study Between GS-7977 and Antiretroviral Therapy (ARV) Combinations of Efavirenz, Tenofovir and Emtricitabine; Efavirenz, Zidovudine and Lamivudine; Atazanavir/Ritonavir, Tenofovir and Emtricitabine; Darunavir/Ritonavir, Tenofovir and Emtricitabine; Raltegravir, Tenofovir and Emtricitabine in Human Immunodeficiency Virus and Hepatitis C Virus (HIV/HCV) Co-infected Patients. Part B: A Phase 2, Open-Label Study to Investigate the Efficacy and Safety of GS-7977 With Peginterferon Alfa 2a and Ribavirin for 12 Weeks in Treatment-Naïve HIV/HCV Co-infected Patients.

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Part A: Evaluate whether Sofosbuvir will significantly influence the PK parameters of Antiretroviral Therapy (ART) in healthy HIV/HCV co-infected subjects. [ Time Frame: Part A: 7 days ] [ Designated as safety issue: No ]
    Part A: Evaluate whether sofosbuvir will significantly influence the PK parameters of Atazanavir/ritonavir (ATV/r), Efavirenz (EFV), Tenofovir (TDF), Emtricitabine(FTC),Zidovudine (ZDV), Lamivudine (3TC), Darunavir/ritonavir (DRV/r) or Raltegravir (RAL) in healthy HIV/HCV co-infected subjects.

  • Part B: Efficacy of Sofosbuvir + Peginterferon Alfa 2a (PEG) + Ribavirin (RBV) [ Time Frame: Part B: 12 weeks after discontinuation of therapy ] [ Designated as safety issue: No ]
    Part B: To determine the efficacy of treatment with Sofosbuvir + PEG + RBV as measured by the proportion of subjects with sustained viral response 12 weeks after discontinuation of therapy (SVR12).

  • Part B: To evaluate the safety and tolerability of Sofosbuvir + PEG + RBV as assessed by review of the accumulated safety data, including HIV-RNA and CD4 T-cell percent. [ Time Frame: Part B: Safety and Tolerability on treatment and 30 days post last dose ] [ Designated as safety issue: No ]

Enrollment: 52
Study Start Date: March 2012
Study Completion Date: November 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A: Cohort 1
Participants received sofosbuvir+EFV/TDF/FTC or sofosbuvir+EFV+FTC/FTD for 7 days, coadministered once daily in the evening under fasting conditions.
Drug: Sofosbuvir
Sofosbuvir 400 mg (1 × 400-mg tablet or 2 × 200-mg tablets) administered orally once daily
Other Names:
  • GS-7977
  • PSI-7977
Drug: EFV/FTC/TDF
Efavirenz (EFV) 600 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg fixed-dose combination (FDC) tablet administered orally once daily
Other Name: Atripla®
Experimental: Part A: Cohort 2
Participants received sofosbuvir+EFV+ZDV/3TC for 7 days. Sofosbuvir and EFV were administered once daily in the evening under fasting conditions; ZDV/3TC was administered twice daily, in the morning without regard to food and in the evening on an empty stomach.
Drug: Sofosbuvir
Sofosbuvir 400 mg (1 × 400-mg tablet or 2 × 200-mg tablets) administered orally once daily
Other Names:
  • GS-7977
  • PSI-7977
Drug: EFV
Efavirenz (EFV) 600 mg tablet administered orally once daily
Other Name: Sustiva®
Drug: ZDV/3TC
Zidovudine (ZDV) 300 mg/lamivudine (3TC) 150 mg FDC tablet administered orally twice daily
Other Name: Combivir®
Experimental: Part A: Cohort 3
Participants received sofosbuvir+ATV boosted with ritonavir (ATV/r)+FTC/TDF for 7 days coadministered once daily in the morning with food.
Drug: Sofosbuvir
Sofosbuvir 400 mg (1 × 400-mg tablet or 2 × 200-mg tablets) administered orally once daily
Other Names:
  • GS-7977
  • PSI-7977
Drug: ATV
Atazanavir 400 mg tablet administered orally once daily
Drug: Ritonavir
Ritonavir (RTV, /r) 100 mg tablet administered orally once daily
Drug: FTC/TDF
FTC/TDF FDC tablet administered orally once daily
Other Name: Truvada®
Experimental: Part A: Cohort 4
Participants received sofosbuvir+DRV boosted with ritonavir (DRV/R)+FTC/TDF for 7 days coadministered once daily in the morning with food.
Drug: Sofosbuvir
Sofosbuvir 400 mg (1 × 400-mg tablet or 2 × 200-mg tablets) administered orally once daily
Other Names:
  • GS-7977
  • PSI-7977
Drug: FTC/TDF
FTC/TDF FDC tablet administered orally once daily
Other Name: Truvada®
Drug: DRV
Darunavir (DRV) 800 mg (2 × 400 mg tablets) administered orally once daily
Experimental: Part A: Cohort 5
Participants received sofosbuvir+RAL+FTC/TDF for 7 days. Sofosbuvir and TFC/TDF were administered once daily in the morning with food; RAL was administered twice daily, in the morning without regard to food and in the evening without regard to food.
Drug: Sofosbuvir
Sofosbuvir 400 mg (1 × 400-mg tablet or 2 × 200-mg tablets) administered orally once daily
Other Names:
  • GS-7977
  • PSI-7977
Drug: FTC/TDF
FTC/TDF FDC tablet administered orally once daily
Other Name: Truvada®
Drug: RAL
Raltegravir (RAL) 400 mg administered administered orally twice daily
Experimental: Part B
Participants received sofosbuvir+PEG+RBV for 12 weeks and were monitored for up to 24 weeks following the last dose of study medication.
Drug: Sofosbuvir
Sofosbuvir 400 mg (1 × 400-mg tablet or 2 × 200-mg tablets) administered orally once daily
Other Names:
  • GS-7977
  • PSI-7977
Drug: PEG
Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection
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:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Healthy according to medical history and physical examination with exception of HCV and HIV diagnoses
  • Confirmation of Chronic HCV infection
  • Confirmation of Chronic HIV-1 infection
  • On a stable protocol approved HIV antiretroviral (ARV) regimen with undetectable HIV-RNA
  • Agree to use two forms of highly effective contraception for the duration of the study and 6 months after the last dose of study medication
  • Subjects must be naive to treatment for chronic HCV infection

Exclusion Criteria:

  • Known or suspected cirrhosis
  • History of any other clinically significant chronic liver disease
  • A history consistent with decompensated liver disease.
  • Use of any prohibited medications as defined by the protocol
  • Pregnant or nursing female or male with pregnant female partner
  • Contraindication to PEG or RBV therapy (for Part B)
  • Clinically relevant drug or alcohol abuse
  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: NCT01565889

Locations
Puerto Rico
Fundacion de Investigacion de Diego
San Juan, Puerto Rico, 00927
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Anuj Gaggar, MD/PhD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01565889     History of Changes
Other Study ID Numbers: P7977-1910
Study First Received: March 27, 2012
Last Updated: December 20, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Hepatitis
Hepatitis A
Hepatitis C
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
Flaviviridae Infections
Ritonavir
Tenofovir
Efavirenz
Peginterferon alfa-2a
Emtricitabine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 09, 2014