Switch Study to Evaluate F/TAF in HIV-1 Positive Participants Who Are Virologically Suppressed on Regimens Containing FTC/TDF

NCT02121795 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-US-311-10892013-005138-39
• Study Type: interventional
• Target: 668
• Locations: 7 countries
• Sites: 78

Brief Summary

This study will evaluate the efficacy of switching from emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) fixed dose combination (FDC) to emtricitabine/tenofovir alafenamide (F/TAF) FDC in HIV-1 positive participants who are virologically suppressed on regimens containing FTC/TDF. This study will consist of a 96 week double-blind treatment period. After Week 96, all participants will continue on blinded study drug treatment and attend visits every 12 weeks until treatment assignments are unblinded. All participants will return for an unblinding visit and will be given the option to receive open-label F/TAF and attend visits every 12 weeks until F/TAF is commercially available, or the sponsor terminates the F/TAF clinical development program.

Conditions

HIV-1 Infection

Keywords

HIV; HIV-1 Positive; Virologically-suppressed

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis

  The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response 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 Outcomes (9)

• Percentage Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48

  Baseline; Week 48

• Percentage Change From Baseline in Spine BMD at Week 48

  Baseline; Week 48

• Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis

  Week 48

• Change From Baseline in CD4+ Cell Count at Week 48

  Baseline; Week 48

• Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Defined by the FDA Snapshot Analysis

  Week 96

Study Arms (2)

F/TAF + 3rd Agent

EXPERIMENTAL

Participants will receive F/TAF (200/25 mg or 200/10 mg) plus FTC/TDF placebo while remaining on an allowed third antiretroviral agent of the participant's pre-existing treatment regimen, for 96 weeks. Dosing of F/TAF will be dependent on the third agent of the participants' pre-existing treatment regimen.

Drug: F/TAF; Drug: Allowed third antiretroviral agent; Drug: FTC/TDF Placebo

FTC/TDF + 3rd Agent

ACTIVE COMPARATOR

Participants will receive FTC/TDF plus F/TAF placebo while remaining on an allowed third antiretroviral agent of the participant's pre-existing treatment regimen, for 96 weeks.

Drug: FTC/TDF; Drug: Allowed third antiretroviral agent; Drug: F/TAF Placebo

Interventions

FTC/TDF DRUG

200/300 mg FDC tablets administered orally once daily

Also known as: Truvada®

FTC/TDF + 3rd Agent

F/TAF DRUG

Tablets administered orally once daily

Also known as: Descovy®

F/TAF + 3rd Agent

Allowed third antiretroviral agent DRUG

An allowed third antiretroviral agent of the participant's pre-existing regimen may include one of the following: ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted lopinavir (LPV/r), ritonavir-boosted darunavir (DRV/r), efavirenz (EFV; Sustiva®), rilpivirine (RPV; Edurant®), nevirapine (NVP;Viramune®), raltegravir (RAL; Isentress®), dolutegravir (DTG;Tivicay®), and maraviroc (MVC; Selzentry®).

F/TAF + 3rd Agent; FTC/TDF + 3rd Agent

FTC/TDF Placebo DRUG

Tablets administered orally once daily

F/TAF + 3rd Agent

F/TAF Placebo DRUG

Tablets administered orally once daily

FTC/TDF + 3rd Agent

Eligibility Criteria

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

You may qualify if:

• Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
• Currently receiving antiretroviral regimen containing FTC/TDF in combination with one third agent for ≥ 6 consecutive months prior to screening.
• Plasma HIV-1 RNA levels \< 50 copies/mL for at least 6 months preceding the screening visit (measured at least twice using the same assay) and not experienced two consecutive HIV-1 RNA above detectable levels after achieving a confirmed (two consecutive) HIV-1 RNA below detectable levels on the current regimen in the past year.
• Plasma HIV-1 RNA should be \< 50 copies/mL at the screening visit.
• Normal electrocardiogram (ECG)
• Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × the upper limit of the normal range (ULN)
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin (individuals with documented Gilbert's syndrome or with Atazanavir-associated hyperbilirubinemia may have total bilirubin up to 5 x ULN)
• Adequate hematologic function
• Serum amylase ≤ 5 × ULN
• Females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active, or practice abstinence from screening throughout the duration of the study treatment and for 30 days following the last dose of the study drug.
• Females 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 at screening within the post-menopausal range based on the Central Laboratory reference range.
• Females 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.
• Males must agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 30 days following the last study drug dose.

You may not qualify if:

• A new AIDS-defining condition diagnosed within the 30 days prior to screening
• Hepatitis C virus (HCV) antibody positive and HCV RNA detectable
• Individuals experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
• Individuals receiving ongoing treatment with bisphosphonate to treat bone disease (eg, osteoporosis)
• Females who are breastfeeding
• Positive serum pregnancy test
• Have an implanted defibrillator or pacemaker
• Current alcohol or substance use judged by the investigator to potentially interfere with study compliance
• A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy 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 Day 1 Visit
• Individuals receiving ongoing therapy with any of the medications not to be used with FTC, TAF, TDF or other antiretroviral third agents.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (78)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Spectrum Medical Group

Phoenix, Arizona, 85012, United States

Location

Pacific Oaks Medical Group

Beverly Hills, California, 90211, United States

Location

Kaiser Permanente

Hayward, California, 94545, United States

Location

Tarrant County ID Associates

Los Angeles, California, 90036, United States

Location

Southern California Men's Medical Group

Los Angeles, California, 90069, United States

Location

Highland Hospital - Alameda Health System (formerly Alameda County medical Center)

Oakland, California, 94602, United States

Location

Kaiser Permanente Sacramento Medical Center

Sacramento, California, 95825, United States

Location

La Playa Medical Group and Clinical Research

San Diego, California, 92103, United States

Location

Kaiser Permanente Medical Group San Francisco

San Francisco, California, 94118, United States

Location

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Kaiser Permanente Colorado

Denver, Colorado, 80205, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Apex Research LLC

Denver, Colorado, 80209, United States

Location

Dupont Circle Physician's Group

Washington D.C., District of Columbia, 20009, United States

Location

Whitman-Walker Health

Washington D.C., District of Columbia, 20009, United States

Location

Capital Medical Associates

Washington D.C., District of Columbia, 20036, United States

Location

Medical Faculty Associates

Washington D.C., District of Columbia, 20037, United States

Location

TheraFirst Medical Center

Fort Lauderdale, Florida, 33308, United States

Location

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

Fort Lauderdale, Florida, 33316, United States

Location

Midway Immunology and Research Center

Ft. Pierce, Florida, 34982, United States

Location

Tarrant County Infectious Disease Associates

Miami, Florida, 33133, United States

Location

AIDS Healthcare Foundation

Miami Beach, Florida, 33139, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

AIDS Healthcare Foundation

Tampa, Florida, 33602, United States

Location

AIDS Research & Treatment Center of the Treasure Coast

Vero Beach, Florida, 32960, United States

Location

Triple O Research Institute PA

West Palm Beach, Florida, 33401, United States

Location

Atlanta ID Group

Atlanta, Georgia, 30309, United States

Location

AIDS Research Consortium of Atlanta

Atlanta, Georgia, 30312, United States

Location

Mercer University School of Medicine

Macon, Georgia, 31201, United States

Location

Community Research Initiative of New England

Boston, Massachusetts, 02111, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Be Well Medical Center

Berkley, Michigan, 48072, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

The Kc Care Clinic Site 5580

Kansas City, Missouri, 64111, United States

Location

St. Louis University

St Louis, Missouri, 63110, United States

Location

Southampton Healthcare, Inc.

St Louis, Missouri, 63139, United States

Location

Prime Healthcare Services - St Michael's LLC d/b/a Saint Michael's Medical Center

Newark, New Jersey, 07102, United States

Location

South Jersey Infectious Disease

Somers Point, New Jersey, 08244, United States

Location

Southwest CARE Center

Santa Fe, New Mexico, 87505, United States

Location

New York Hospital Queens

Flushing, New York, 11355, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Ricky K. Hsu, MD, PC

New York, New York, 10011, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Infectious Disease Consultants, PA

Charlotte, North Carolina, 28209, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Central Texas Clinical Research

Austin, Texas, 78705, United States

Location

AIDS Arms, Inc

Dallas, Texas, 75215, United States

Location

Southwest Infectious Disease Clinical Research, Inc

Dallas, Texas, 75219, United States

Location

North Texas Infectious Diseases Consulants

Dallas, Texas, 75246, United States

Location

AIDS Arms, Inc./Trinity Health & Wellness Center

Fort Worth, Texas, 76104, United States

Location

Therapeutic Concepts, PA

Houston, Texas, 77004, United States

Location

Gordon E. Crofoot MD PA

Houston, Texas, 77098, United States

Location

Peter Shalit, MD

Seattle, Washington, 98104, United States

Location

Premier Clinical Research

Spokane, Washington, 99202, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

CHU Saint-Pierre of Brussels

Brussels, 1000, Belgium

Location

Vancouver Infectious Disease Research and Care Centre

Vancouver, British Columbia, V6Z 2C7, Canada

Location

Ottawa Hospital-General Campus

Ottawa, Ontario, K1Y 4E9, Canada

Location

Maple Leaf Medical Clinic/Maple Leaf Research

Toronto, Ontario, M5B 1L6, Canada

Location

University Health Network/Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

University Hospital of Montpellier (CHU-Gui de Chauliac)

Montpellier, 34295, France

Location

CHU de Nantes Hopital de l'Hotel Dieu

Nantes, 44093, France

Location

Hopital Bichat Claude Bernard

Paris, 75018, France

Location

Hôpital Tenon

Paris, 75020, France

Location

Centre Hospitalier de Tourcoing

Tourcoing, 59208, France

Location

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

IRCCS Ospedale San Raffaele, Centro San Luigi

Milan, 20127, Italy

Location

Hope Clinical Research

San Juan, 00901, Puerto Rico

Location

Clinical Research Puerto Rico Inc

San Juan, 00909, Puerto Rico

Location

University of Puerto Rico School of Medicine

San Juan, 00935, Puerto Rico

Location

Brighton and Sussex University Hospitals

Brighton, BN2 1ES, United Kingdom

Location

Barts Health NHS Trust

London, E1 1BB, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

King's College Hospital

London, SE5 9RJ, United Kingdom

Location

Chelsea and Westminster Hospital

London, SW10 9TH, United Kingdom

Location

Manchester Centre for Sexual Health

Manchester, M13 0FH, United Kingdom

Location

Related Publications (1)

• Gallant JE, Daar ES, Raffi F, Brinson C, Ruane P, DeJesus E, Johnson M, Clumeck N, Osiyemi O, Ward D, Morales-Ramirez J, Yan M, Abram ME, Plummer A, Cheng AK, Rhee MS. Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate given as fixed-dose combinations containing emtricitabine as backbones for treatment of HIV-1 infection in virologically suppressed adults: a randomised, double-blind, active-controlled phase 3 trial. Lancet HIV. 2016 Apr;3(4):e158-65. doi: 10.1016/S2352-3018(16)00024-2. Epub 2016 Mar 14.

  PMID: 27036991 DERIVED

MeSH Terms

Interventions

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; emtricitabine tenofovir alafenamide

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

There were no limitations affecting the analysis or results.

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

ClinicalTrialDisclosures@gilead.com

1-833-445-3230

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2014
• First Posted: April 24, 2014
• Study Start: May 6, 2014
• Primary Completion: August 12, 2015
• Study Completion: March 1, 2019
• Last Updated: March 12, 2020
• Results First Posted: November 30, 2016

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

CA (4); PR (3); GB (6); IT (2); US (57); BE (1); FR (5)