Safety and Efficacy of E/C/F/TAF (Genvoya®) Versus E/C/F/TDF (Stribild®) in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Study Description

Brief Summary:

The primary objective of this study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya®; E/C/F/TAF) fixed-dose combination (FDC) versus elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (Stribild®; E/C/F/TDF) FDC in HIV-1 infected, antiretroviral treatment-naive adults.

Condition or disease	Intervention/treatment	Phase
Acquired Immunodeficiency Syndrome; HIV Infections	Drug: E/C/F/TDF; Drug: E/C/F/TAF Placebo; Drug: E/C/F/TAF; Drug: E/C/F/TDF Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 279 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single Tablet Regimen Versus Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen in HIV-1 Infected, Antiretroviral Treatment-Naive Adults
• Actual Study Start Date: December 28, 2011
• Actual Primary Completion Date: October 17, 2012
• Actual Study Completion Date: August 22, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: E/C/F/TAF; E/C/F/TAF plus E/C/F/TDF placebo for at least 48 weeks	Drug: E/C/F/TAF; 150/150/200/10 mg FDC tablet administered orally once daily; Other Name: Genvoya®; Drug: E/C/F/TDF Placebo; Tablet administered orally once daily
Active Comparator: E/C/F/TDF; E/C/F/TDF plus E/C/F/TAF placebo for at least 48 weeks	Drug: E/C/F/TDF; 150/150/200/300 mg FDC tablet administered orally once daily; Other Name: Stribild®; Drug: E/C/F/TAF Placebo; Tablet administered orally once daily
Experimental: E/C/F/TAF Open-Label; Following study unblinding, participants from the E/C/F/TAF and E/C/F/TDF arms may have the option to receive E/C/F/TAF during an open-label extension phase. Also, participants who are actively participating in a Gilead-sponsored study of cobicistat-boosted darunavir plus nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) who have reached the protocol-defined secondary endpoint (Week 48) and remain virologically suppressed are eligible to participate and receive E/C/F/TAF in this open-label extension phase.	Drug: E/C/F/TAF; 150/150/200/10 mg FDC tablet administered orally once daily; Other Name: Genvoya®

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 [ Time Frame: Week 24 ]
   The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Secondary Outcome Measures :

1. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 [ Time Frame: Week 48 ]
   The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
2. Change From Baseline in log10 HIV-1 RNA at Weeks 24 and 48 [ Time Frame: Baseline; Weeks 24 and 48 ]
3. Change From Baseline in CD4+ Cell Count at Weeks 24 and 48 [ Time Frame: Baseline; Weeks 24 and 48 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• Ability to understand and sign a written informed consent form
• Plasma HIV 1 RNA levels ≥ 5,000 copies/mL
• No prior use of any approved or experimental anti-HIV drug for any length of time
• Screening genotype report must show sensitivity to TDF and emtricitabine (FTC)
• Normal ECG
• Adequate renal function: Estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula
• Hepatic transaminases ≤ 2.5 x upper limit of the normal range (ULN)
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
• Adequate hematologic function
• CD4+ cell count > 50 cells/µL
• Serum amylase ≤ 5 x ULN
• Normal thyroid-stimulating hormone (TSH)
• Females of childbearing potential must have a negative serum pregnancy test
• Females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 30 days following the last dose of study drugs
• Female subjects who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
• Female subjects who are postmenopausal must have documentation of cessation of menses for ≥ 12 months and hormonal failure
• Female subjects who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level test at screening
• Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 90 days following discontinuation of investigational medicinal product
• Age ≥ 18 years
• Life expectancy ≥ 1 year

Key Exclusion Criteria:

• New AIDS-defining condition diagnosed within the 30 days prior to screening
• Hepatitis B surface Antigen positive
• Hepatitis C Antibody positive
• Proven acute hepatitis in the 30 days prior to study entry
• Subjects experiencing decompensated cirrhosis
• Females who are breastfeeding
• Positive serum pregnancy test (female of childbearing potential)
• Have an implanted defibrillator or pacemaker
• Receiving ongoing therapy with any of the disallowed medications, including drugs not to be used with elvitegravir and cobicistat
• Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study
• Current alcohol or substance
• History of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma or resected, non-invasive cutaneous squamous carcinoma
• Active, serious infections (other than HIV 1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline
• Participation in any other clinical trial without prior approval is prohibited while participating in this trial
• Medications contraindicated for use with emtricitabine or tenofovir disoproxil fumarate
• Any known allergies to the excipients of E/C/F/TAF or E/C/F/TDF FDC tablets
• Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

  Show 41 Study Locations

Sponsors and Collaborators

Gilead Sciences

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

More Information

Publications of Results:

Sax PE, Zolopa A, Brar I, Elion R, Ortiz R, Post F, Wang H, Callebaut C, Martin H, Fordyce MW, McCallister S. Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study. J Acquir Immune Defic Syndr. 2014 Sep 1;67(1):52-8. doi: 10.1097/QAI.0000000000000225.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01497899 History of Changes
• Other Study ID Numbers: GS-US-292-0102
• First Posted: December 23, 2011
• Results First Posted: January 8, 2016
• Last Update Posted: November 19, 2018
• Last Verified: August 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.
• URL: http://www.gilead.com/research/disclosure-and-transparency

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gilead Sciences:

HIV-1; HIV; Treatment-Naive

Additional relevant MeSH terms:

HIV Infections; Immunologic Deficiency Syndromes; Acquired Immunodeficiency Syndrome; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immune System Diseases; Slow Virus Diseases; Anti-Retroviral Agents; Tenofovir; Cobicistat; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Genvoya; Antiviral Agents; Anti-Infective Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors