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

Phase 2
Completed
Conditions
Acquired Immunodeficiency Syndrome
HIV Infections
Interventions
Drug: E/C/F/TAF Placebo
Drug: E/C/F/TDF Placebo
Registration Number
NCT01497899
Lead Sponsor
Gilead Sciences
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
279
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
E/C/F/TDFE/C/F/TAF PlaceboE/C/F/TDF plus E/C/F/TAF placebo for at least 48 weeks
E/C/F/TAF Open-LabelE/C/F/TAFFollowing 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.
E/C/F/TAFE/C/F/TAFE/C/F/TAF plus E/C/F/TDF placebo for at least 48 weeks
E/C/F/TAFE/C/F/TDF PlaceboE/C/F/TAF plus E/C/F/TDF placebo for at least 48 weeks
E/C/F/TDFE/C/F/TDFE/C/F/TDF plus E/C/F/TAF placebo for at least 48 weeks
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24Week 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
NameTimeMethod
Change From Baseline in CD4+ Cell Count at Weeks 24 and 48Baseline; Weeks 24 and 48
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48Week 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.

Change From Baseline in log10 HIV-1 RNA at Weeks 24 and 48Baseline; Weeks 24 and 48

Trial Locations

Locations (41)

Kaiser Permanente

🇺🇸

Los Angeles, California, United States

Gary J. Richmond,M.D.,P.A.

🇺🇸

Fort Lauderdale, Florida, United States

Infectious Disease Specialists of Atlanta

🇺🇸

Decatur, Georgia, United States

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

North Shore University Hospital / Division of Infectious Diseases

🇺🇸

Manhasset, New York, United States

Peter J. Ruane, MD, Inc.

🇺🇸

Los Angeles, California, United States

AHF Research Center

🇺🇸

Beverly Hills, California, United States

Stanford University

🇺🇸

Palo Alto, California, United States

Anthony Mills MD, Inc

🇺🇸

Los Angeles, California, United States

St. Joseph Heritage Healthcare

🇺🇸

Orange, California, United States

Kaiser Permanente Medical Group

🇺🇸

Sacramento, California, United States

Dupont Circle Physician's Group

🇺🇸

Washington, District of Columbia, United States

Capital Medical Associates, PC

🇺🇸

Washington, District of Columbia, United States

IDOCF/ValuhealthMD, LLC

🇺🇸

Orlando, Florida, United States

Wohlfeiler, Piperato and Associates, LLC

🇺🇸

Miami Beach, Florida, United States

Howard Brown Health Center

🇺🇸

Chicago, Illinois, United States

Be Well Medical Center

🇺🇸

Berkley, Michigan, United States

Central West Clinical Research Inc

🇺🇸

Saint Louis, Missouri, United States

ID Consultants, P.A.

🇺🇸

Charlotte, North Carolina, United States

Therapeutic Concepts, PA

🇺🇸

Houston, Texas, United States

Tarrant County Infectious Disease Associates

🇺🇸

Fort Worth, Texas, United States

Southwest Infectious Disease Clinical Research Inc

🇺🇸

Dallas, Texas, United States

Gordon E. Crofoot, MD., PA

🇺🇸

Houston, Texas, United States

Peter Shalit, M.D.

🇺🇸

Seattle, Washington, United States

DCOL Center for Clinical Research

🇺🇸

Longview, Texas, United States

Clinical Research Puerto Rico

🇵🇷

San Juan, Puerto Rico

Kaiser Permanente Medical Group-Clinical Trials Unit

🇺🇸

San Francisco, California, United States

Spectrum Medical Group

🇺🇸

Phoenix, Arizona, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

La Playa Medical Group and Clinical Research

🇺🇸

San Diego, California, United States

Metropolis Medical

🇺🇸

San Francisco, California, United States

Henry Ford Health System

🇺🇸

Detroit, Michigan, United States

Hennepin County Medical Center

🇺🇸

Minneapolis, Minnesota, United States

University of Alabama at Birmingham (UAB)

🇺🇸

Birmingham, Alabama, United States

Apex Research, LLC

🇺🇸

Denver, Colorado, United States

St. Joseph's Comprehensive Research Institute

🇺🇸

Tampa, Florida, United States

East Bay AIDS Center

🇺🇸

Oakland, California, United States

Mercer University Mercer Medicine

🇺🇸

Macon, Georgia, United States

Whitman-Walker Health

🇺🇸

Washington, District of Columbia, United States

Orlando Immunology Center

🇺🇸

Orlando, Florida, United States

University of South Carolina School of Medicine Division of Infectious Disease

🇺🇸

Columbia, South Carolina, United States

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