D/C/F/TAF Versus COBI-boosted DRV Plus FTC/TDF in HIV-1 Infected, Antiretroviral Treatment Naive Adults

Study Overview
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Brief Summary
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This study is to evaluate the safety and efficacy darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed dose combination (FDC) tablet versus darunavir (DRV)+cobicistat (COBI)+emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) in HIV-1 infected, antiretroviral treatment-naive adults as determined by the achievement of HIV-1 RNA < 50 copies/mL at Week 24.

Official Title
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A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of Darunavir/Cobicistat/Emtricitabine/GS-7340 Single Tablet Regimen Versus Cobicistat-boosted Darunavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate Fixed Dose Combination in HIV-1 Infected, Antiretroviral Treatment Naive Adults

Conditions
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Acquired Immunodeficiency Syndrome, HIV Infections

Intervention / Treatment
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* Drug: D/C/F/TAF
* Drug: DRV
* Drug: COBI
* Drug: FTC/TDF
* Drug: D/C/F/TAF Placebo
* Drug: DRV Placebo
* Drug: COBI Placebo
* Drug: FTC/TDF Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (≥ 18 years) males or non-pregnant females Ability to understand and sign a written informed consent form General medical condition which does not interfere with the assessments and the completion of the trial Plasma HIV-1 RNA levels ≥ 5,000 copies/mL CD4+ cell count > 50 cells/µL Treatment-naive: No prior use of any approved or experimental anti-HIV drug for any length of time Screening genotype report must show sensitivity to DRV, TDF and FTC Normal ECG Adequate renal function: Estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula Hepatic transaminases ≤ 2.5 x upper limit of normal (ULN) Total bilirubin ≤ 1.5 mg/dL Serum amylase ≤ 5 x ULN Adequate hematologic function Normal thyroid-stimulating hormone (TSH) Females of childbearing potential must have a negative serum pregnancy test Females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 30 days following the last dose of study drugs Female subjects who are postmenopausal must have documentation of cessation of menses for ≥ 12 months and hormonal failure Female subjects 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 test Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 90 days following discontinuation of investigational medicinal product Exclusion Criteria: A new AIDS defining condition diagnosed within the 30 days prior to screening Hepatitis B surface antigen positive Hepatitis C antibody positive Proven acute hepatitis in the 30 days prior to study entry Have a history or experiencing decompensated cirrhosis Current alcohol or substance use that potentially interferes with study compliance Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma Females who are breastfeeding Positive serum pregnancy test (female of childbearing potential) Female subjects who utilize non-estrogen hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing Have an implanted defibrillator or pacemaker Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline Participation in any other clinical trial without prior approval is prohibited while participating in this trial Receiving ongoing therapy with any of the disallowed medications, including drugs not to be used with darunavir and cobicistat Note: darunavir is a sulfonamide. Participants who previously experienced a sulfonamide allergy will be allowed to enter the trial. To date, no potential for cross sensitivity between drugs in the sulfonamide class and darunavir has been identified in patients participating in Phase 2 and Phase 3 trials.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: D/C/F/TAF<br>D/C/F/TAF FDC tablet plus DRV placebo plus COBI placebo plus FTC/TDF placebo | Drug: D/C/F/TAF<br>* DRV 800 mg/COBI 150 mg/FTC 200 mg/TAF 10 mg FDC tablet administered orally once daily<br>Drug: DRV Placebo<br>* DRV placebo tablet administered orally once daily<br>Drug: COBI Placebo<br>* COBI placebo tablet administered orally once daily<br>Drug: FTC/TDF Placebo<br>* FTC/TDF placebo tablet administered orally once daily<br>|
| Active Comparator: DRV+COBI+FTC/TDF<br>DRV tablet plus COBI tablet plus FTC/TDF 200/300 mg FDC tablet plus D/C/F/TAF placebo | Drug: DRV<br>* DRV 800 mg (2 × 400 mg tablets) administered orally once daily<br>* Other names: Prezista®;Drug: COBI<br>* COBI 150 mg tablet administered orally once daily<br>* Other names: GS-9350;Drug: FTC/TDF<br>* FTC 200 mg/TDF 300 mg FDC tablet administered orally once daily<br>* Other names: Truvada®;Drug: D/C/F/TAF Placebo<br>* D/C/F/TAF placebo tablet administered orally once daily<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 24 | The 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, along with study drug discontinuation status. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | The 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, along with study drug discontinuation status. | Week 48 | 
| Change From Baseline in HIV-1 RNA at Week 24 |  | Baseline; Week 24 | 
| Change From Baseline in HIV-1 RNA at Week 48 |  | Baseline; Week 48 | 
| Change From Baseline in CD4+ Cell Count at Week 24 |  | Baseline; Week 24 | 
| Change From Baseline in CD4+ Cell Count at Week 48 |  | Baseline; Week 48 | 

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