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

HIV-1 Infection Clinical Trial

Official title:

A Phase 3, Randomized, Double-Blind, Switch Study to Evaluate F/TAF in HIV-1 Positive Subjects Who Are Virologically Suppressed on Regimens Containing FTC/TDF

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02121795
• Other study ID #: GS-US-311-1089
• Secondary ID: 2013-005138-39
• Status: Completed
• Phase: Phase 3
• Start date: May 6, 2014
• Est. completion date: March 1, 2019

Study information

• Verified date: February 2020
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 668
• Est. completion date: March 1, 2019
• Est. primary completion date: August 12, 2015
• 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, 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.

Key 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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• FTC/TDF
200/300 mg FDC tablets administered orally once daily
• F/TAF
Tablets administered orally once daily
• 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®).
• FTC/TDF Placebo
Tablets administered orally once daily
• F/TAF Placebo
Tablets administered orally once daily

Locations

Country	Name	City	State
Belgium	CHU Saint-Pierre of Brussels	Brussels
Canada	Ottawa Hospital-General Campus	Ottawa	Ontario
Canada	Maple Leaf Medical Clinic/Maple Leaf Research	Toronto	Ontario
Canada	University Health Network/Toronto General Hospital	Toronto	Ontario
Canada	Vancouver Infectious Disease Research and Care Centre	Vancouver	British Columbia
France	University Hospital of Montpellier (CHU-Gui de Chauliac)	Montpellier
France	CHU de Nantes Hopital de l'Hotel Dieu	Nantes
France	Hopital Bichat Claude Bernard	Paris
France	Hôpital Tenon	Paris
France	Centre Hospitalier de Tourcoing	Tourcoing
Italy	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo
Italy	IRCCS Ospedale San Raffaele, Centro San Luigi	Milano
Puerto Rico	Clinical Research Puerto Rico Inc	San Juan
Puerto Rico	Hope Clinical Research	San Juan
Puerto Rico	University of Puerto Rico School of Medicine	San Juan
United Kingdom	Brighton and Sussex University Hospitals	Brighton
United Kingdom	Barts Health NHS Trust	London
United Kingdom	Chelsea and Westminster Hospital	London
United Kingdom	King's College Hospital	London
United Kingdom	Royal Free London NHS Foundation Trust	London
United Kingdom	Manchester Centre for Sexual Health	Manchester
United States	AIDS Research Consortium of Atlanta	Atlanta	Georgia
United States	Atlanta ID Group	Atlanta	Georgia
United States	Central Texas Clinical Research	Austin	Texas
United States	Be Well Medical Center	Berkley	Michigan
United States	Pacific Oaks Medical Group	Beverly Hills	California
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Community Research Initiative of New England	Boston	Massachusetts
United States	Jacobi Medical Center	Bronx	New York
United States	Montefiore Medical Center	Bronx	New York
United States	Infectious Disease Consultants, PA	Charlotte	North Carolina
United States	Ohio State University Medical Center	Columbus	Ohio
United States	AIDS Arms, Inc	Dallas	Texas
United States	North Texas Infectious Diseases Consulants	Dallas	Texas
United States	Southwest Infectious Disease Clinical Research, Inc	Dallas	Texas
United States	Apex Research LLC	Denver	Colorado
United States	Kaiser Permanente Colorado	Denver	Colorado
United States	National Jewish Health	Denver	Colorado
United States	New York Hospital Queens	Flushing	New York
United States	Gary J. Richmond,M.D.,P.A.	Fort Lauderdale	Florida
United States	TheraFirst Medical Center	Fort Lauderdale	Florida
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	AIDS Arms, Inc./Trinity Health & Wellness Center	Fort Worth	Texas
United States	Kaiser Permanente	Hayward	California
United States	Gordon E. Crofoot MD PA	Houston	Texas
United States	Therapeutic Concepts, PA	Houston	Texas
United States	The Kc Care Clinic Site 5580	Kansas City	Missouri
United States	Southern California Men's Medical Group	Los Angeles	California
United States	Tarrant County ID Associates	Los Angeles	California
United States	Mercer University School of Medicine	Macon	Georgia
United States	North Shore University Hospital	Manhasset	New York
United States	Tarrant County Infectious Disease Associates	Miami	Florida
United States	AIDS Healthcare Foundation	Miami Beach	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Ricky K. Hsu, MD, PC	New York	New York
United States	Prime Healthcare Services - St Michael's LLC d/b/a Saint Michael's Medical Center	Newark	New Jersey
United States	Highland Hospital - Alameda Health System (formerly Alameda County medical Center)	Oakland	California
United States	Orlando Immunology Center	Orlando	Florida
United States	Spectrum Medical Group	Phoenix	Arizona
United States	Kaiser Permanente Sacramento Medical Center	Sacramento	California
United States	Southampton Healthcare, Inc.	Saint Louis	Missouri
United States	St. Louis University	Saint Louis	Missouri
United States	La Playa Medical Group and Clinical Research	San Diego	California
United States	Kaiser Permanente Medical Group San Francisco	San Francisco	California
United States	Southwest CARE Center	Santa Fe	New Mexico
United States	Peter Shalit, MD	Seattle	Washington
United States	South Jersey Infectious Disease	Somers Point	New Jersey
United States	Premier Clinical Research	Spokane	Washington
United States	AIDS Healthcare Foundation	Tampa	Florida
United States	Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center	Torrance	California
United States	AIDS Research & Treatment Center of the Treasure Coast	Vero Beach	Florida
United States	Capital Medical Associates	Washington	District of Columbia
United States	Dupont Circle Physician's Group	Washington	District of Columbia
United States	Medical Faculty Associates	Washington	District of Columbia
United States	Whitman-Walker Health	Washington	District of Columbia
United States	Triple O Research Institute PA	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Italy,  Puerto Rico,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48	Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.	Baseline; Week 48
Secondary	Percentage Change From Baseline in Spine BMD at Week 48	Spine BMD was assessed by DXA scan.	Baseline; Week 48
Secondary	Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis	The percentage of participants achieving HIV-1 RNA < 20 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	Change From Baseline in CD4+ Cell Count at Week 48		Baseline; Week 48
Secondary	Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Defined by the FDA Snapshot Analysis	The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 96 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 96
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 96 as Defined by the FDA Snapshot Analysis	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 96 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 96
Secondary	Percentage Change From Baseline in Hip BMD at Week 96	Hip BMD was assessed by DXA scan.	Baseline; Week 96
Secondary	Percentage Change From Baseline in Spine BMD at Week 96	Spine BMD was assessed by DXA scan.	Baseline; Week 96
Secondary	Change From Baseline in CD4+ Cell Count at Week 96		Baseline; Week 96