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.

NCT01565889 | Completed Phase 1 Results

• 1 other identifier: P7977-1910
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C; HIV

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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

Secondary Outcomes (2)

• Part B: Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)

  Posttreatment Weeks 4 and 24

• Part B: Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse

  Posttreatment Weeks 4 and 24

Other Outcomes (2)

• Part B: On-treatment HCV RNA

  Up to 8 weeks

• Part B: On-treatment HIV RNA

  Up to 8 weeks

Study Arms (6)

Part A: SOF+EFV/FTC/TDF (Cohort 1)

EXPERIMENTAL

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.

Drug: SOF; Drug: EFV/FTC/TDF

Part A: SOF+EFV+ZDV/3TC (Cohort 2)

EXPERIMENTAL

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.

Drug: SOF; Drug: EFV; Drug: ZDV/3TC

Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3)

EXPERIMENTAL

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.

Drug: SOF; Drug: ATV; Drug: Ritonavir; Drug: FTC/TDF

Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4)

EXPERIMENTAL

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.

Drug: SOF; Drug: Ritonavir; Drug: FTC/TDF; Drug: DRV

Part A: SOF+RAL+FTC/TDF (Cohort 5)

EXPERIMENTAL

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.

Drug: SOF; Drug: FTC/TDF; Drug: RAL

Part B: SOF+PEG+RBV

EXPERIMENTAL

Participants will receive SOF+PEG+RBV for 12 weeks.

Drug: SOF; Drug: PEG; Drug: RBV

Interventions

SOF DRUG

Sofosbuvir (SOF) 400 mg (1 × 400 mg tablet or 2 × 200 mg tablets) administered orally once daily

Also known as: Sovaldi®, GS-7977, PSI-7977

Part A: SOF+EFV+ZDV/3TC (Cohort 2); Part A: SOF+EFV/FTC/TDF (Cohort 1); Part A: SOF+RAL+FTC/TDF (Cohort 5); Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3); Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4); Part B: SOF+PEG+RBV

EFV/FTC/TDF DRUG

Efavirenz (EFV) 600 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg fixed-dose combination (FDC) tablet administered orally once daily

Also known as: Atripla®

Part A: SOF+EFV/FTC/TDF (Cohort 1)

EFV DRUG

Efavirenz (EFV) 600 mg tablet administered orally once daily

Also known as: Sustiva®

Part A: SOF+EFV+ZDV/3TC (Cohort 2)

ZDV/3TC DRUG

Zidovudine (ZDV) 300 mg/lamivudine (3TC) 150 mg FDC tablet administered orally twice daily

Also known as: Combivir®

Part A: SOF+EFV+ZDV/3TC (Cohort 2)

ATV DRUG

Atazanavir (ATV) 400 mg tablet administered orally once daily

Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3)

Ritonavir DRUG

Ritonavir (RTV) 100 mg tablet administered orally once daily

Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3); Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4)

FTC/TDF DRUG

FTC/TDF (200/300 mg) FDC tablet administered orally once daily

Also known as: Truvada®

Part A: SOF+RAL+FTC/TDF (Cohort 5); Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3); Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4)

DRV DRUG

Darunavir (DRV) 800 mg (2 × 400 mg tablets) administered orally once daily

Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4)

RAL DRUG

Raltegravir (RAL) 400 mg administered administered orally twice daily

Part A: SOF+RAL+FTC/TDF (Cohort 5)

PEG DRUG

Pegylated interferon alfa (PEG) 180 μg administered once weekly by subcutaneous injection

Also known as: Pegasys®

Part B: SOF+PEG+RBV

RBV DRUG

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)

Also known as: Ribasphere®

Part B: SOF+PEG+RBV

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (1)

Fundacion de Investigacion de Diego

San Juan, 00927, Puerto Rico

Location

Related Publications (1)

• 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.

  PMID: 25622055 DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

Sofosbuvir; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; efavirenz; lamivudine, zidovudine drug combination; Ritonavir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Oxazines; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Drug Combinations; Pharmaceutical Preparations; Thiazoles; Sulfur Compounds; Azoles; Deoxyribonucleosides; Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences, Inc.

ClinicalTrialDisclosures@gilead.com

Study Officials

• Anuj Gaggar, MD/PhD

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2012
• First Posted: March 29, 2012
• Study Start: March 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: November 1, 2013
• Last Updated: October 1, 2014
• Results First Posted: October 1, 2014

Record last verified: 2014-09

Locations

PR (1)