Study to Evaluate Switching From Regimens Consisting of a Nonnucleoside Reverse Transcriptase Inhibitor Plus Emtricitabine and Tenofovir DF to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppressed, HIV-1 Infected Patients

Study Overview
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Brief Summary
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This study will evaluate the noninferiority of Stribild® (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF)) single-tablet regimen (STR) relative to regimens consisting of a nonnucleoside reverse transcriptase inhibitor (NNRTI) plus Truvada® (FTC/TDF) in maintaining HIV-1 RNA < 50 copies/mL at Week 48 in virologically suppressed, HIV-1 infected adults. This study will also evaluate the safety, tolerability, and efficacy of the two regimens through 96 weeks of treatment.

Official Title
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A Phase 3b Randomized, Open Label Study to Evaluate Switching From Regimens Consisting of a Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) Plus Emtricitabine (FTC) and Tenofovir DF (TDF) to the Elvitegravir/Cobicistat/ Emtricitabine/Tenofovir Disoproxil Fumarate Single-Tablet Regimen (EVG/COBI/FTC/TDF) in Virologically Suppressed, HIV 1 Infected Patients

Conditions
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Acquired Immunodeficiency Syndrome, HIV Infections

Intervention / Treatment
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* Drug: NNRTI
* Drug: FTC/TDF
* Drug: Stribild


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand and sign a written informed consent form Be stable on the current formulation(s) of an antiretroviral regimen consisting of an NNRTI plus FTC/TDF for ≥ 6 consecutive months preceding the screening visit. This includes those who began a regimen with individual drug components and subsequently simplified to include a fixed-dose combination formulation of the same drugs. Be on the first or second antiretroviral regimen with documented undetectable plasma HIV 1 RNA levels for ≥ 6 months preceding the screening visit No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI) for any length of time Documented historical genotype prior to starting initial antiretroviral therapy showing no known resistance to TDF or FTC HIV RNA < 50 copies/mL at screening Normal ECG Hepatic transaminases ≤ 5 × the upper limit of the normal range (ULN) Total bilirubin ≤ 1.5 mg/dL Adequate hematologic function Serum amylase ≤ 5 × ULN Estimated glomerular filtration rate ≥ 70 mL/min Females of childbearing potential must agree to utilize protocol recommended contraception methods or be nonheterosexually active, practice sexual abstinence from screening throughout the duration of the study period and for 12 weeks for participants on EFV/FTC/TDF or efavirenz or 30 days for the rest of participants following the last dose of study drug Female participants 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 Male participants must agree to utilize protocol-recommended methods of contraception during heterosexual intercourse or be nonheterosexually active, and practice sexual abstinence from the screening visit. Age ≥ 18 years Exclusion Criteria: New AIDS-defining condition diagnosed within the 30 days prior to screening Females who are breastfeeding Positive serum pregnancy test (female of childbearing potential) Receiving drug treatment for hepatitis C, or those who are anticipated to receive treatment for hepatitis C during the course of the study Experiencing decompensated cirrhosis Have an implanted defibrillator or pacemaker Current alcohol or substance abuse that would interfere with compliance A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma. Persons with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of baseline and must not be anticipated to require systemic therapy during the study. Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study Receiving ongoing therapy with any of the medications, including drugs not to be used with elvitegravir, cobicistat, FTC, or TDF; or those with any known allergies to the excipients of E/C/F/TDF tablets, or FTC/TDF tablets No anticipated need to initiate drugs during the study that are contraindicated Receiving other investigational drugs Participation in any other clinical trial Any other clinical condition or prior therapy that would make the participant unsuitable for the study or unable to comply with the dosing requirements

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stribild<br>Participants will switch from their baseline treatment regimen to Stribild for up to 96 weeks, and may continue to receive Stribild in the extension phase. | Drug: Stribild<br>* Stribild® (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate; E/C/F/TDF) (150/150/200/300 mg) STR administered orally once daily with food<br>|
| Active Comparator: NNRTI+FTC/TDF<br>Participants will stay on their baseline treatment regimen antiretroviral regimen consisting of an NNRTI plus FTC/TDF for up to 96 weeks, and may switch to Stribild in the extension phase. | Drug: NNRTI<br>* NNRTI agents administered according to prescribing information; allowed NNRTIs include efavirenz (EFV), nevirapine, or rilpivirine.<br>Drug: FTC/TDF<br>* FTC/TDF (200/300 mg) administered according to prescribing information<br>* Other names: Truvada;Drug: Stribild<br>* Stribild® (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate; E/C/F/TDF) (150/150/200/300 mg) STR administered orally once daily with food<br>|

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 | The FDA-defined Snapshot algorithm was used, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time. | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 | The FDA-defined Snapshot algorithm was used, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, HIV-1, Treatment Experienced