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

NCT ID: NCT02121795

Last Updated: 2020-03-12

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

668 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-05-06

Study Completion Date

2019-03-01

Brief Summary

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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.

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Detailed Description

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Conditions

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HIV-1 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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F/TAF + 3rd Agent

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.

Group Type EXPERIMENTAL

F/TAF

Intervention Type DRUG

Tablets administered orally once daily

Allowed third antiretroviral agent

Intervention Type 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®).

FTC/TDF Placebo

Intervention Type DRUG

Tablets administered orally once daily

FTC/TDF + 3rd Agent

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.

Group Type ACTIVE_COMPARATOR

FTC/TDF

Intervention Type DRUG

200/300 mg FDC tablets administered orally once daily

Allowed third antiretroviral agent

Intervention Type 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 Placebo

Intervention Type DRUG

Tablets administered orally once daily

Interventions

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FTC/TDF

200/300 mg FDC tablets administered orally once daily

Intervention Type DRUG

F/TAF

Tablets administered orally once daily

Intervention Type DRUG

Allowed third antiretroviral agent

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®).

Intervention Type DRUG

FTC/TDF Placebo

Tablets administered orally once daily

Intervention Type DRUG

F/TAF Placebo

Tablets administered orally once daily

Intervention Type DRUG

Other Intervention Names

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Truvada® Descovy®

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Spectrum Medical Group

Phoenix, Arizona, United States

Site Status

Pacific Oaks Medical Group

Beverly Hills, California, United States

Site Status

Kaiser Permanente

Hayward, California, United States

Site Status

Tarrant County ID Associates

Los Angeles, California, United States

Site Status

Southern California Men's Medical Group

Los Angeles, California, United States

Site Status

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

Oakland, California, United States

Site Status

Kaiser Permanente Sacramento Medical Center

Sacramento, California, United States

Site Status

La Playa Medical Group and Clinical Research

San Diego, California, United States

Site Status

Kaiser Permanente Medical Group San Francisco

San Francisco, California, United States

Site Status

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

Torrance, California, United States

Site Status

Kaiser Permanente Colorado

Denver, Colorado, United States

Site Status

National Jewish Health

Denver, Colorado, United States

Site Status

Apex Research LLC

Denver, Colorado, United States

Site Status

Dupont Circle Physician's Group

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

Site Status

Whitman-Walker Health

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

Site Status

Capital Medical Associates

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

Site Status

Medical Faculty Associates

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

Site Status

TheraFirst Medical Center

Fort Lauderdale, Florida, United States

Site Status

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

Fort Lauderdale, Florida, United States

Site Status

Midway Immunology and Research Center

Ft. Pierce, Florida, United States

Site Status

Tarrant County Infectious Disease Associates

Miami, Florida, United States

Site Status

AIDS Healthcare Foundation

Miami Beach, Florida, United States

Site Status

Orlando Immunology Center

Orlando, Florida, United States

Site Status

AIDS Healthcare Foundation

Tampa, Florida, United States

Site Status

AIDS Research & Treatment Center of the Treasure Coast

Vero Beach, Florida, United States

Site Status

Triple O Research Institute PA

West Palm Beach, Florida, United States

Site Status

Atlanta ID Group

Atlanta, Georgia, United States

Site Status

AIDS Research Consortium of Atlanta

Atlanta, Georgia, United States

Site Status

Mercer University School of Medicine

Macon, Georgia, United States

Site Status

Community Research Initiative of New England

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Be Well Medical Center

Berkley, Michigan, United States

Site Status

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Site Status

The Kc Care Clinic Site 5580

Kansas City, Missouri, United States

Site Status

St. Louis University

St Louis, Missouri, United States

Site Status

Southampton Healthcare, Inc.

St Louis, Missouri, United States

Site Status

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

Newark, New Jersey, United States

Site Status

South Jersey Infectious Disease

Somers Point, New Jersey, United States

Site Status

Southwest CARE Center

Santa Fe, New Mexico, United States

Site Status

New York Hospital Queens

Flushing, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Ricky K. Hsu, MD, PC

New York, New York, United States

Site Status

Jacobi Medical Center

The Bronx, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Infectious Disease Consultants, PA

Charlotte, North Carolina, United States

Site Status

Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

Central Texas Clinical Research

Austin, Texas, United States

Site Status

AIDS Arms, Inc

Dallas, Texas, United States

Site Status

Southwest Infectious Disease Clinical Research, Inc

Dallas, Texas, United States

Site Status

North Texas Infectious Diseases Consulants

Dallas, Texas, United States

Site Status

AIDS Arms, Inc./Trinity Health & Wellness Center

Fort Worth, Texas, United States

Site Status

Therapeutic Concepts, PA

Houston, Texas, United States

Site Status

Gordon E. Crofoot MD PA

Houston, Texas, United States

Site Status

Peter Shalit, MD

Seattle, Washington, United States

Site Status

Premier Clinical Research

Spokane, Washington, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

CHU Saint-Pierre of Brussels

Brussels, , Belgium

Site Status

Vancouver Infectious Disease Research and Care Centre

Vancouver, British Columbia, Canada

Site Status

Ottawa Hospital-General Campus

Ottawa, Ontario, Canada

Site Status

Maple Leaf Medical Clinic/Maple Leaf Research

Toronto, Ontario, Canada

Site Status

University Health Network/Toronto General Hospital

Toronto, Ontario, Canada

Site Status

University Hospital of Montpellier (CHU-Gui de Chauliac)

Montpellier, , France

Site Status

CHU de Nantes Hopital de l'Hotel Dieu

Nantes, , France

Site Status

Hopital Bichat Claude Bernard

Paris, , France

Site Status

Hôpital Tenon

Paris, , France

Site Status

Centre Hospitalier de Tourcoing

Tourcoing, , France

Site Status

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, , Italy

Site Status

IRCCS Ospedale San Raffaele, Centro San Luigi

Milan, , Italy

Site Status

Hope Clinical Research

San Juan, , Puerto Rico

Site Status

Clinical Research Puerto Rico Inc

San Juan, , Puerto Rico

Site Status

University of Puerto Rico School of Medicine

San Juan, , Puerto Rico

Site Status

Brighton and Sussex University Hospitals

Brighton, , United Kingdom

Site Status

Barts Health NHS Trust

London, , United Kingdom

Site Status

Royal Free London NHS Foundation Trust

London, , United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

Chelsea and Westminster Hospital

London, , United Kingdom

Site Status

Manchester Centre for Sexual Health

Manchester, , United Kingdom

Site Status

Countries

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United States Belgium Canada France Italy Puerto Rico United Kingdom

References

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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.

Reference Type DERIVED
PMID: 27036991 (View on PubMed)

Other Identifiers

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2013-005138-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-311-1089

Identifier Type: -

Identifier Source: org_study_id

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