Clinical trial NCT01497899: Safety and Efficacy of E/C/F/TAF (Genvoya®) Versus E/C/F/TDF (Stribild®) in HIV-1 Infected, Antiretroviral Treatment-Naive Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acquired Immunodeficiency Syndrome
HIV Infections
Keywords: HIV-1
HIV
Treatment-Naive
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-12-23
Enrollment: 279
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
timeFrame: Week 48
measure: Change From Baseline in log10 HIV-1 RNA at Weeks 24 and 48
timeFrame: Baseline; Weeks 24 and 48
measure: Change From Baseline in CD4+ Cell Count at Weeks 24 and 48
timeFrame: Baseline; Weeks 24 and 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham (UAB)
state: Alabama
city: Phoenix
country: United States
facility: Spectrum Medical Group
state: Arizona
city: Beverly Hills
country: United States
facility: AHF Research Center
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: Los Angeles
country: United States
facility: Peter J. Ruane, MD, Inc.
state: California
city: Los Angeles
country: United States
facility: Anthony Mills MD, Inc
state: California
city: Oakland
country: United States
facility: East Bay AIDS Center
state: California
city: Orange
country: United States
facility: St. Joseph Heritage Healthcare
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Medical Group
state: California
city: San Diego
country: United States
facility: La Playa Medical Group and Clinical Research
state: California
city: San Francisco
country: United States
facility: Metropolis Medical
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente Medical Group-Clinical Trials Unit
state: California
city: Denver
country: United States
facility: Apex Research, LLC
state: Colorado
city: Washington
country: United States
facility: Dupont Circle Physician's Group
state: District of Columbia
city: Washington
country: United States
facility: Whitman-Walker Health
state: District of Columbia
city: Washington
country: United States
facility: Capital Medical Associates, PC
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Gary J. Richmond,M.D.,P.A.
state: Florida
city: Miami Beach
country: United States
facility: Wohlfeiler, Piperato and Associates, LLC
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Orlando
country: United States
facility: IDOCF/ValuhealthMD, LLC
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Comprehensive Research Institute
state: Florida
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta
state: Georgia
city: Macon
country: United States
facility: Mercer University Mercer Medicine
state: Georgia
city: Chicago
country: United States
facility: Howard Brown Health Center
state: Illinois
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Saint Louis
country: United States
facility: Central West Clinical Research Inc
state: Missouri
city: Manhasset
country: United States
facility: North Shore University Hospital / Division of Infectious Diseases
state: New York
city: Charlotte
country: United States
facility: ID Consultants, P.A.
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbia
country: United States
facility: University of South Carolina School of Medicine Division of Infectious Disease
state: South Carolina
city: Dallas
country: United States
facility: Southwest Infectious Disease Clinical Research Inc
state: Texas
city: Fort Worth
country: United States
facility: Tarrant County Infectious Disease Associates
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, PA
state: Texas
city: Houston
country: United States
facility: Gordon E. Crofoot, MD., PA
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
city: Seattle
country: United States
facility: Peter Shalit, M.D.
state: Washington
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.