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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01497899
• Other study ID #: GS-US-292-0102
• Status: Completed
• Phase: Phase 2
• Start date: December 28, 2011
• Est. completion date: August 22, 2016

Study information

• Verified date: August 2017
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 279
• Est. completion date: August 22, 2016
• Est. primary completion date: October 17, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes

Intervention

Drug:
• E/C/F/TDF
150/150/200/300 mg FDC tablet administered orally once daily
• E/C/F/TAF Placebo
Tablet administered orally once daily
• E/C/F/TAF
150/150/200/10 mg FDC tablet administered orally once daily
• E/C/F/TDF Placebo
Tablet administered orally once daily

Locations

Country	Name	City	State
Puerto Rico	Clinical Research Puerto Rico	San Juan
United States	Be Well Medical Center	Berkley	Michigan
United States	AHF Research Center	Beverly Hills	California
United States	University of Alabama at Birmingham (UAB)	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	ID Consultants, P.A.	Charlotte	North Carolina
United States	Howard Brown Health Center	Chicago	Illinois
United States	University of South Carolina School of Medicine Division of Infectious Disease	Columbia	South Carolina
United States	Southwest Infectious Disease Clinical Research Inc	Dallas	Texas
United States	Infectious Disease Specialists of Atlanta	Decatur	Georgia
United States	Apex Research, LLC	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Gary J. Richmond,M.D.,P.A.	Fort Lauderdale	Florida
United States	Tarrant County Infectious Disease Associates	Fort Worth	Texas
United States	Gordon E. Crofoot, MD., PA	Houston	Texas
United States	Therapeutic Concepts, PA	Houston	Texas
United States	DCOL Center for Clinical Research	Longview	Texas
United States	Anthony Mills MD, Inc	Los Angeles	California
United States	Kaiser Permanente	Los Angeles	California
United States	Peter J. Ruane, MD, Inc.	Los Angeles	California
United States	Mercer University Mercer Medicine	Macon	Georgia
United States	North Shore University Hospital / Division of Infectious Diseases	Manhasset	New York
United States	Wohlfeiler, Piperato and Associates, LLC	Miami Beach	Florida
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	East Bay AIDS Center	Oakland	California
United States	St. Joseph Heritage Healthcare	Orange	California
United States	IDOCF/ValuhealthMD, LLC	Orlando	Florida
United States	Orlando Immunology Center	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	Spectrum Medical Group	Phoenix	Arizona
United States	Kaiser Permanente Medical Group	Sacramento	California
United States	Central West Clinical Research Inc	Saint Louis	Missouri
United States	La Playa Medical Group and Clinical Research	San Diego	California
United States	Kaiser Permanente Medical Group-Clinical Trials Unit	San Francisco	California
United States	Metropolis Medical	San Francisco	California
United States	Peter Shalit, M.D.	Seattle	Washington
United States	St. Joseph's Comprehensive Research Institute	Tampa	Florida
United States	Capital Medical Associates, PC	Washington	District of Columbia
United States	Dupont Circle Physician's Group	Washington	District of Columbia
United States	Whitman-Walker Health	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 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.	Week 24
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 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.	Week 48
Secondary	Change From Baseline in log10 HIV-1 RNA at Weeks 24 and 48		Baseline; Weeks 24 and 48
Secondary	Change From Baseline in CD4+ Cell Count at Weeks 24 and 48		Baseline; Weeks 24 and 48