Switch Study to Evaluate the Safety and Efficacy of Emtricitabine/Rilpivirine/Tenofovir Alafenamide (FTC/RPV/TAF) Fixed Dose Combination (FDC) in HIV-1 Positive Adults Who Are Virologically Suppressed on Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate (FTC/RPV/TDF)

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the noninferiority of switching to emtricitabine/rilpivirine /tenofovir alafenamide (FTC/RPV/TAF) fixed-dose combination (FDC) as compared to continuing FTC/RPV/tenofovir disoproxil fumarate (TDF) FDC (FTC/RPV/TDF) in virologically suppressed HIV-1 infected participants.

Official Title
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A Phase 3b, Randomized, Double-Blind Switch Study to Evaluate the Safety and Efficacy of Emtricitabine/Rilpivirine/Tenofovir Alafenamide (FTC/RPV/TAF) Fixed Dose Combination (FDC) in HIV-1 Positive Subjects Who Are Virologically Suppressed on Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate (FTC/RPV/TDF)

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: FTC/RPV/TAF
* Drug: FTC/RPV/TDF Placebo
* Drug: FTC/RPV/TDF
* Drug: FTC/RPV/TAF Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures Currently receiving FTC/RPV/TDF FDC for ≥ 6 consecutive months preceding the screening visit Documented plasma HIV-1 RNA levels < 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is > 50 copies/mL) for ≥ 6 months preceding the screening visit. After reaching HIV-1 RNA < 50 copies/mL, single values of HIV-1 RNA ≥ 50 copies/mL followed by resuppression, are allowed Have no documented resistance to any of the study agents at any time in the past HIV-1 RNA < 50 copies/mL at the screening visit Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN) Total bilirubin ≤ 1.5 mg/dL (≤ 26 μmol/L), or normal direct bilirubin Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm^3 (1.00 GI/L); platelets ≥ 50,000/mm^3 (50 GI/L); hemoglobin ≥ 8.5 g/dL (85 g/L)) Serum amylase ≤ 5 × ULN (individuals with serum amylase > 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant) Adequate renal function: Estimated glomerular filtration rate ≥ 50 mL/min (1.17 mL/sec) according to the Cockcroft-Gault formula Key Exclusion Criteria: Hepatitis B surface antigen (HBsAg) positive Hepatitis C antibody positive with detectable hepatitis C virus (HCV) RNA (individuals who have HCV antibody but no detectable HCV RNA are eligible to enroll) Individuals experiencing or with a medical history of decompensated cirrhosis (e.g., ascites, encephalopathy, etc.) Females who are breastfeeding Positive serum pregnancy test Current alcohol or substance use judged by the Investigator to potentially interfere with individual's 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. Individuals with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Baseline/Day 1 and must not be anticipated to require systemic therapy during the study Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline/Day 1 Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial Individuals receiving ongoing therapy with any of the disallowed medications listed in the protocol, including drugs not to be used with FTC, RPV and/or TAF; or individuals with any known allergies to the excipients of FTC/RPV/TAF Note: Other Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FTC/RPV/TAF<br>FTC/RPV/TAF plus FTC/RPV/TDF placebo for at least 96 weeks. | Drug: FTC/RPV/TAF<br>* 200/25/25 mg FDC tablets administered orally once daily<br>* Other names: Odefsey®;Drug: FTC/RPV/TDF Placebo<br>* Tablets administered orally once daily<br>|
| Active Comparator: FTC/RPV/TDF<br>FTC/RPV/TDF plus FTC/RPV/TAF placebo for at least 96 weeks. | Drug: FTC/RPV/TDF<br>* 200/25/300 mg FDC tablets administered orally once daily<br>* Other names: Eviplera®;Drug: FTC/RPV/TAF Placebo<br>* Tablets administered orally once daily<br>|
| Experimental: Open Label Extension Phase<br>After the Week 96 visit is completed, participants will be given the option to receive open label FTC/RPV/TAF for up to an additional 48 weeks. In countries where FTC/RPV/TAF is not yet commercially available, participants will be given the option to receive open-label FTC/RPV/TAF, and attend visits every 12 weeks until FTC/RPV/TAF becomes commercially available, or until Gilead Sciences elects to discontinue the study, whichever occurs first. | Drug: FTC/RPV/TAF<br>* 200/25/25 mg FDC tablets administered orally once daily<br>* Other names: Odefsey®;|

What is the study measuring?
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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 US FDA-Defined Snapshot Algorithm | The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the US FDA-defined 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. | Week 48 | 

Secondary 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 US FDA-Defined Snapshot Algorithm | The percentage of participants with 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. | Week 48 | 
| Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm | The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 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. | Week 96 | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm | The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 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. | Week 96 | 
| Change From Baseline in CD4+ Cell Count at Week 48 |  | Baseline; Week 48 | 
| Change From Baseline in CD4+ Cell Count at Week 96 |  | Baseline; Week 96 | 
| Percent 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 | 
| Percent Change From Baseline in Hip BMD at Week 96 | Hip BMD was assessed by DXA scan. | Baseline; Week 96 | 
| Percent Change From Baseline in Spine BMD at Week 48 | Spine BMD was assessed by DXA scan. | Baseline; Week 48 | 
| Percent Change From Baseline in Spine BMD at Week 96 | Spine BMD was assessed by DXA scan. | Baseline; Week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV