Safety and Efficacy of Cobicistat-boosted Darunavir in HIV Infected Adults

Study Overview
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Brief Summary
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This study is to evaluate the safety and tolerability of cobicistat-boosted darunavir plus two fully active nucleoside analogue reverse transcriptase inhibitors in HIV 1 infected, antiretroviral treatment-naive and treatment-experienced adults with no darunavir (DRV) resistance-associated mutations. After the Week 48 Visit, participants will be given the option to participate in an open-label rollover phase to receive cobicistat and attend visits every 12 weeks until it becomes commercially available, or until Gilead Sciences elects to terminate development of cobicistat.

Official Title
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A Phase 3b, Open-Label, Single Arm Study to Evaluate the Safety and Efficacy of Cobicistat-boosted Darunavir Plus Two Fully Active Nucleoside Reverse Transcriptase Inhibitors in HIV-1 Infected, Antiretroviral Treatment-Naïve and -Experienced Adults With No Darunavir Resistance-associated Mutations

Conditions
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Acquired Immunodeficiency Syndrome, HIV Infections

Intervention / Treatment
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* Drug: COBI
* Drug: DRV
* Drug: NRTIs


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 that does not interfere with the assessments and the completion of the trial Treatment Naive: No prior use of any approved or investigational antiretroviral drug for any length of time OR Treatment Experienced: Stable antiretroviral regimen for at least 12 weeks prior to screening Plasma HIV-1 RNA levels ≥ 1000 copies/mL at Screening Screening genotype report shows full sensitivity to two nucleoside analogue reverse transcriptase inhibitors (NRTIs) and no darunavir resistance-associated mutations Normal electrocardiogram (ECG) Hepatic transaminases ≤ 2.5 × upper limit of normal (ULN) Total bilirubin ≤ 1.5 mg/dL Adequate hematologic function Serum amylase ≤ 2 × ULN and serum lipase ≤ 3 × ULN Adequate renal function: Estimated glomerular filtration rate ≥ 80 mL/min Females of childbearing potential must agree to utilize protocol-recommended methods of contraception, or be nonheterosexually active, practice sexual abstinence or have a vasectomized partner from Screening throughout the duration of the study period and for 30 days following the last dose of study drug. Male subjects must agree to utilize protocol-recommended methods of contraception during heterosexual intercourse from the Screening visit, throughout the duration of the study and for 30 days following discontinuation of investigational medicinal product or be nonheterosexually active, practice sexual abstinence, or be vasectomized. Exclusion Criteria: Previous or current use of darunavir A new AIDS-defining condition diagnosed within the 30 days prior to Screening Females who are breastfeeding Positive serum pregnancy test (if female of childbearing potential) Proven or suspected acute hepatitis in the 30 days prior to study entry Subjects receiving drug treatment for hepatitis C virus (HCV), or subjects who are anticipated to receive treatment for HCV during the course of the study Have a history of ongoing active liver disease or experiencing decompensated cirrhosis irrespective of liver enzyme levels Have an implanted defibrillator or pacemaker Current alcohol or substance use that may interfere with subject study compliance A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline Participation in any other clinical trial Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements. Subjects receiving ongoing therapy with any of the medications, including drugs not to be used with cobicistat, darunavir, or investigator selected NRTIs; or subjects with any known allergies to cobicistat tablets, darunavir tablets or contraindications for the 2 NRTIs as part of the regimen.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COBI-boosted DRV<br>Participants will receive DRV+COBI+2 investigator-selected NRTIs for 48 weeks, and may continue their regimen in the open-label rollover phase. | Drug: COBI<br>* 150 mg tablet administered orally with food once daily<br>* Other names: GS-9350;Drug: DRV<br>* 800 mg (2 x 400 mg tablets) administered orally with food once daily<br>* Other names: TMC114;Drug: NRTIs<br>* Participants will receive 2 nucleoside analogue reverse transcriptase inhibitors (NRTIs) selected by the investigator after resistance testing at screening and administered according to prescribing information. NRTIs may include emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF), zidovudine+FTC/TDF, abacavir (ABC)+TDF, ABC+FTC/TDF, ABC+lamivudine (3TC), or didanosine (DDI)+FTC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Onset of Any Treatment-emergent Grade 3 or 4 Adverse Event Between Baseline and Week 24 |  | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 24 (Snapshot Analysis) |  | Week 24 | 
| Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 48 (Snapshot Analysis) |  | 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 | 
| Percentage of Participants Experiencing Any Treatment-emergent Adverse Event and Any Treatment-emergent Adverse Event Leading to Discontinuation of Study Drug Through Week 24 |  | Up to 24 weeks | 
| Percentage of Participants Experiencing Any Treatment-emergent Adverse Event and Any Treatment-emergent Adverse Event Leading to Discontinuation of Study Drug Through Week 48 |  | Up to 48 weeks | 

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