Back to resultsPart 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.
Primary Purpose
Hepatitis C, HIV
Status
Completed
Phase
Phase 1
Locations
Puerto Rico
Study Type
Interventional
Intervention
SOF
EFV/FTC/TDF
EFV
ZDV/3TC
ATV
Ritonavir
FTC/TDF
DRV
RAL
PEG
RBV
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C
Eligibility 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
Sites / Locations
- Fundacion de Investigacion de Diego
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Part A: SOF+EFV/FTC/TDF (Cohort 1)
Part A: SOF+EFV+ZDV/3TC (Cohort 2)
Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3)
Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4)
Part A: SOF+RAL+FTC/TDF (Cohort 5)
Part B: SOF+PEG+RBV
Arm Description
Participants with a prestudy regimen of EFV/FTC/TDF will receive SOF+EFV/FTC/TDF FDC for 7 days, followed by EFV/FTC/TDF FDC (or EFV+FTC/TDF) for 7 days, coadministered once daily in the evening under fasting conditions.
Participants with a prestudy regimen of EFV+ZDV/3TC will receive SOF+EFV+ZDV/3TC for 7 days followed by EFV+ZDV/3TC for 7 days. Sofosbuvir and EFV will be administered once daily in the evening under fasting conditions; ZDV/3TC will be administered twice daily, in the morning without regard to food and in the evening on an empty stomach.
Participants with a prestudy regimen of RTV+ATV+FTC/TDF will receive SOF+RTV+ATV+FTC/TDF for 7 days followed by RTV+ATV+FTC/TDF for 7 days coadministered once daily in the morning with food.
Participants with a prestudy regimen of RTV+DRV+FTC/TDF will receive SOF+RTV+DRV+FTC/TDF for 7 days followed by RTV+DRV+FTC/TDF for 7 days coadministered once daily in the morning with food.
Participants with a prestudy regimen of RAL+FTC/TDF will receive SOF+RAL+FTC/TDF for 7 days followed by RAL+FTC/TDF for 7 days. Sofosbuvir and FTC/TDF will be administered once daily in the morning with food; RAL will be administered twice daily, in the morning with food and in the evening without regard to food.
Participants will receive SOF+PEG+RBV for 12 weeks.
Outcomes
Primary Outcome Measures
Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7
AUCtau: concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).
Data for this outcome measure were collected for participants in Part A only.
Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7
Cmax: maximum observed concentration of drug in plasma.
Data for this outcome measure were collected for participants in Part A only.
Part B: Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)
SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
Data for this outcome measure were collected for participants in Part B only.
Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)
The percentage of participants discontinuing any study drug due to an adverse event was summarized.
Secondary Outcome Measures
Part B: Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR4 and SVR24 was defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
Data for this outcome measure were collected for participants in Part B only.
Part B: Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse
Viral breakthrough was defined as having confirmed detectable HCV RNA levels (HCV RNA > LLOQ) on treatment after having previously had undetectable HCV RNA levels (HCV RNA < LLOQ) while on treatment.
Viral relapse was defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) at end of treatment, but did not achieve an SVR.
Data for this outcome measure were collected for participants in Part B only.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01565889
Brief Title
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.
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.
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
November 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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, pegylated interferon alpha (PEG) and ribavirin (RBV) in participants with HIV/HCV coinfection.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, HIV
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A: SOF+EFV/FTC/TDF (Cohort 1)
Arm Type
Experimental
Arm Description
Participants with a prestudy regimen of EFV/FTC/TDF will receive SOF+EFV/FTC/TDF FDC for 7 days, followed by EFV/FTC/TDF FDC (or EFV+FTC/TDF) for 7 days, coadministered once daily in the evening under fasting conditions.
Arm Title
Part A: SOF+EFV+ZDV/3TC (Cohort 2)
Arm Type
Experimental
Arm Description
Participants with a prestudy regimen of EFV+ZDV/3TC will receive SOF+EFV+ZDV/3TC for 7 days followed by EFV+ZDV/3TC for 7 days. Sofosbuvir and EFV will be administered once daily in the evening under fasting conditions; ZDV/3TC will be administered twice daily, in the morning without regard to food and in the evening on an empty stomach.
Arm Title
Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3)
Arm Type
Experimental
Arm Description
Participants with a prestudy regimen of RTV+ATV+FTC/TDF will receive SOF+RTV+ATV+FTC/TDF for 7 days followed by RTV+ATV+FTC/TDF for 7 days coadministered once daily in the morning with food.
Arm Title
Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4)
Arm Type
Experimental
Arm Description
Participants with a prestudy regimen of RTV+DRV+FTC/TDF will receive SOF+RTV+DRV+FTC/TDF for 7 days followed by RTV+DRV+FTC/TDF for 7 days coadministered once daily in the morning with food.
Arm Title
Part A: SOF+RAL+FTC/TDF (Cohort 5)
Arm Type
Experimental
Arm Description
Participants with a prestudy regimen of RAL+FTC/TDF will receive SOF+RAL+FTC/TDF for 7 days followed by RAL+FTC/TDF for 7 days. Sofosbuvir and FTC/TDF will be administered once daily in the morning with food; RAL will be administered twice daily, in the morning with food and in the evening without regard to food.
Arm Title
Part B: SOF+PEG+RBV
Arm Type
Experimental
Arm Description
Participants will receive SOF+PEG+RBV for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
SOF
Other Intervention Name(s)
Sovaldi®, GS-7977, PSI-7977
Intervention Description
Sofosbuvir (SOF) 400 mg (1 × 400 mg tablet or 2 × 200 mg tablets) administered orally once daily
Intervention Type
Drug
Intervention Name(s)
EFV/FTC/TDF
Other Intervention Name(s)
Atripla®
Intervention Description
Efavirenz (EFV) 600 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg fixed-dose combination (FDC) tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
EFV
Other Intervention Name(s)
Sustiva®
Intervention Description
Efavirenz (EFV) 600 mg tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
ZDV/3TC
Other Intervention Name(s)
Combivir®
Intervention Description
Zidovudine (ZDV) 300 mg/lamivudine (3TC) 150 mg FDC tablet administered orally twice daily
Intervention Type
Drug
Intervention Name(s)
ATV
Intervention Description
Atazanavir (ATV) 400 mg tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
Ritonavir
Intervention Description
Ritonavir (RTV) 100 mg tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
FTC/TDF
Other Intervention Name(s)
Truvada®
Intervention Description
FTC/TDF (200/300 mg) FDC tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
DRV
Intervention Description
Darunavir (DRV) 800 mg (2 × 400 mg tablets) administered orally once daily
Intervention Type
Drug
Intervention Name(s)
RAL
Intervention Description
Raltegravir (RAL) 400 mg administered administered orally twice daily
Intervention Type
Drug
Intervention Name(s)
PEG
Other Intervention Name(s)
Pegasys®
Intervention Description
Pegylated interferon alfa (PEG) 180 μg administered once weekly by subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
RBV
Other Intervention Name(s)
Ribasphere®
Intervention Description
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)
Primary Outcome Measure Information:
Title
Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7
Description
AUCtau: concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).
Data for this outcome measure were collected for participants in Part A only.
Time Frame
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
Title
Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7
Description
Cmax: maximum observed concentration of drug in plasma.
Data for this outcome measure were collected for participants in Part A only.
Time Frame
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
Title
Part B: Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)
Description
SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
Data for this outcome measure were collected for participants in Part B only.
Time Frame
Posttreatment Week 12
Title
Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)
Description
The percentage of participants discontinuing any study drug due to an adverse event was summarized.
Time Frame
Up to 12 weeks
Secondary Outcome Measure Information:
Title
Part B: Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
Description
SVR4 and SVR24 was defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
Data for this outcome measure were collected for participants in Part B only.
Time Frame
Posttreatment Weeks 4 and 24
Title
Part B: Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse
Description
Viral breakthrough was defined as having confirmed detectable HCV RNA levels (HCV RNA > LLOQ) on treatment after having previously had undetectable HCV RNA levels (HCV RNA < LLOQ) while on treatment.
Viral relapse was defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) at end of treatment, but did not achieve an SVR.
Data for this outcome measure were collected for participants in Part B only.
Time Frame
Posttreatment Weeks 4 and 24
Other Pre-specified Outcome Measures:
Title
Part B: On-treatment HCV RNA
Description
Data for this outcome measure were collected for participants in Part B only.
Time Frame
Up to 8 weeks
Title
Part B: On-treatment HIV RNA
Description
Data for this outcome measure were collected for participants in Part B only.
Time Frame
Up to 8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anuj Gaggar, MD/PhD
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Fundacion de Investigacion de Diego
City
San Juan
ZIP/Postal Code
00927
Country
Puerto Rico
12. IPD Sharing Statement
Citations:
PubMed Identifier
25622055
Citation
Rodriguez-Torres M, Gaggar A, Shen G, Kirby B, Svarovskaia E, Brainard D, Symonds WT, McHutchison JG, Gonzalez M, Rodriguez-Orengo J. Sofosbuvir for chronic hepatitis C virus infection genotype 1-4 in patients coinfected with HIV. J Acquir Immune Defic Syndr. 2015 Apr 15;68(5):543-9. doi: 10.1097/QAI.0000000000000516.
Results Reference
derived
Learn more about this trial
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.
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