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.

HIV Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01565889
• Other study ID #: P7977-1910
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 27, 2012
• Last updated: September 25, 2014
• Start date: March 2012
• Est. completion date: November 2013

Study information

• Verified date: September 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: November 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• HIV

Intervention

Drug:
• SOF
Sofosbuvir (SOF) 400 mg (1 × 400 mg tablet or 2 × 200 mg tablets) administered orally once daily
• 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
• EFV
Efavirenz (EFV) 600 mg tablet administered orally once daily
• ZDV/3TC
Zidovudine (ZDV) 300 mg/lamivudine (3TC) 150 mg FDC tablet administered orally twice daily
• ATV
Atazanavir (ATV) 400 mg tablet administered orally once daily
• Ritonavir
Ritonavir (RTV) 100 mg tablet administered orally once daily
• FTC/TDF
FTC/TDF (200/300 mg) FDC tablet administered orally once daily
• DRV
Darunavir (DRV) 800 mg (2 × 400 mg tablets) administered orally once daily
• RAL
Raltegravir (RAL) 400 mg administered administered orally twice daily
• PEG
Pegylated interferon alfa (PEG) 180 µg administered once weekly by subcutaneous injection
• 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)

Locations

Country	Name	City	State
Puerto Rico	Fundacion de Investigacion de Diego	San Juan

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Part B: On-treatment HCV RNA	Data for this outcome measure were collected for participants in Part B only.	Up to 8 weeks	No
Other	Part B: On-treatment HIV RNA	Data for this outcome measure were collected for participants in Part B only.	Up to 8 weeks	No
Primary	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.	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose	No
Primary	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.	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose	No
Primary	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.	Posttreatment Week 12	No
Primary	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.	Up to 12 weeks	No
Secondary	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.	Posttreatment Weeks 4 and 24	No
Secondary	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.	Posttreatment Weeks 4 and 24	No