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

Study Overview
=================
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.

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

Conditions
-----------------
HIV-1 Infection

Intervention / Treatment
-----------------
* Drug: FTC/TDF
* Drug: F/TAF
* Drug: Allowed third antiretroviral agent
* Drug: FTC/TDF Placebo
* Drug: F/TAF Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: F/TAF + 3rd Agent<br>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<br>* Tablets administered orally once daily<br>* Other names: Descovy®;Drug: Allowed third antiretroviral agent<br>* 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®).<br>Drug: FTC/TDF Placebo<br>* Tablets administered orally once daily<br>|
| Active Comparator: FTC/TDF + 3rd Agent<br>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<br>* 200/300 mg FDC tablets administered orally once daily<br>* Other names: Truvada®;Drug: Allowed third antiretroviral agent<br>* 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®).<br>Drug: F/TAF Placebo<br>* Tablets administered orally once daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Percentage Change From Baseline in Spine BMD at Week 48 | Spine BMD was assessed by DXA scan. | Baseline; Week 48 | 
| 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 | 
| 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 | 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 | 
| 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 | 
| Percentage Change From Baseline in Hip BMD at Week 96 | Hip BMD was assessed by DXA scan. | Baseline; Week 96 | 
| Percentage Change From Baseline in Spine BMD at Week 96 | Spine BMD was assessed by DXA scan. | Baseline; Week 96 | 
| Change From Baseline in CD4+ Cell Count at Week 96 |  | Baseline; Week 96 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV, HIV-1 Positive, Virologically-suppressed