Efficacy of Tenofovir Alafenamide Versus Placebo Added to a Failing Regimen Followed by Treatment With Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Atazanavir in HIV-1 Positive, Antiretroviral Treatment-Experienced Adults
- Conditions
- HIVHIV InfectionsAcquired Immunodeficiency Syndrome
- Interventions
- Drug: TAFDrug: PlaceboDrug: E/C/F/TAFDrug: Current failing ARV regimenDrug: ATV
- Registration Number
- NCT01967940
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objective of this study is to evaluate the efficacy of tenofovir alafenamide (TAF) versus placebo, each administered with the existing, failing antiretroviral (ARV) regimen. There are 2 parts to this study: Part 1 and Part 2.
Part 1 consists of 2 cohorts, starting with a sentinel cohort, in which participants will be enrolled to receive open-label TAF in addition to their current failing ARV regimen. This cohort will then be followed by a randomized, double-blind, cohort to compare the addition of TAF or placebo in HIV-1 positive adults who are failing their current ARV regimen.
In Part 2, all participants who complete Part 1 of the study will discontinue their failing ARV regimen and TAF or placebo for a 14-day washout period. Following the washout period, all participants who received TAF in Part 1 and have a \> 0.5 log10 decline in HIV-1 RNA will receive elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single-tablet regimen (STR) plus atazanavir (ATV) once daily for 48 weeks. Participants who received TAF who have a ≤ 0.5 log10 decline in HIV-1 RNA will be discontinued from the study and will not be eligible to continue into Part 2 of the study. All participants who received placebo in Part 1 will be eligible to participate in Part 2 regardless of their viral load change. After completion of Part 2, all participants will be eligible to continue to receive E/C/F/TAF plus ATV in the extension phase until E/C/F/TAF becomes commercially available, or until Gilead Sciences terminates development of E/C/F/TAF in the applicable country.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 55
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Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
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Currently taking a failing ARV regimen
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Plasma HIV-1 RNA ≥ 500 copies/mL but ≤ 100,000 copies/mL at screening
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Normal ECG
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Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
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Alanine aminotransferase (AST)/aspartate aminotransferase (AST) ≤ 5 × the upper limit of the normal range (ULN)
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Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
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Adequate hematologic function
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Serum amylase ≤ 5 × ULN
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Females may enter the study if it is confirmed that she is:
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Not pregnant or nursing
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Of non-childbearing potential (ie, have had a hysterectomy, both ovaries removed, medically documented ovarian failure, or are postmenopausal women > 54 years of age with cessation [for ≥ 12 months] of previously occurring menses), or
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Of childbearing potential and agrees to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following study drug dosing
- 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.
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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.
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Males must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose.
Key
- A new AIDS-defining condition diagnosed within the 30 days prior to screening
- Hepatitis B surface antigen (HBsAg) positive
- Hepatitis C antibody positive (individuals with positive hepatitis C virus (HCV) antibody and without detectable HCV RNA are permitted to enroll)
- History of integrase inhibitor use
- Screening or historical genotype reports shows Q151M or T69ins or more than 3 TAMs.
- Screening or historical genotype report shows resistance to integrase inhibitors
- Individuals experiencing decompensated cirrhosis
- Current alcohol or substance use
- 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 Part 1, 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 Part 1, Day 1
- Any other clinical condition or prior therapy that 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
- Receiving ongoing therapy with any disallowed medications, including any drugs not to be used with elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide or known allergies to the excipients of E/C/F/TAF STR
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1 Sentinel Cohort (TAF) TAF TAF + their current failing ARV regimen for 10 days in Part 1 Part 1 Sentinel Cohort (TAF) Current failing ARV regimen TAF + their current failing ARV regimen for 10 days in Part 1 Part 1 Randomized Cohort (TAF) TAF Following review of safety and efficacy data from the Sentinel Cohort, participants will be randomized to receive TAF + their current failing ARV regimen for 10 days in Part 1. Part 1 Randomized Cohort (TAF) Current failing ARV regimen Following review of safety and efficacy data from the Sentinel Cohort, participants will be randomized to receive TAF + their current failing ARV regimen for 10 days in Part 1. Part 1 Randomized Cohort (Placebo) Placebo Following review of safety and efficacy data from the Sentinel Cohort, participants will be randomized to receive placebo + their current failing ARV regimen for 10 days in Part 1. Part 1 Randomized Cohort (Placebo) Current failing ARV regimen Following review of safety and efficacy data from the Sentinel Cohort, participants will be randomized to receive placebo + their current failing ARV regimen for 10 days in Part 1. Part 2 E/C/F/TAF+ATV E/C/F/TAF Following a 14-day period to confirm eligibility, participants in the Randomized Cohort TAF group with a \> 0.5 log10 decline in HIV-1 RNA and all participants completing the Randomized Cohort Placebo group will receive E/C/F/TAF+ATV for 48 weeks in Part 2. After completion of Part 2, all participants will be eligible to continue to receive E/C/F/TAF plus ATV in the extension phase until E/C/F/TAF becomes commercially available, or until Gilead Sciences terminates development of E/C/F/TAF in the applicable country. Part 2 E/C/F/TAF+ATV ATV Following a 14-day period to confirm eligibility, participants in the Randomized Cohort TAF group with a \> 0.5 log10 decline in HIV-1 RNA and all participants completing the Randomized Cohort Placebo group will receive E/C/F/TAF+ATV for 48 weeks in Part 2. After completion of Part 2, all participants will be eligible to continue to receive E/C/F/TAF plus ATV in the extension phase until E/C/F/TAF becomes commercially available, or until Gilead Sciences terminates development of E/C/F/TAF in the applicable country.
- Primary Outcome Measures
Name Time Method Part 1: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 10 Day 10
- Secondary Outcome Measures
Name Time Method Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Any Treatment-Emergent Adverse Event Through Week 24 Up to Week 24 Part 1: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Day 10 Baseline; Day 10 Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities Through Week 24 Up to Week 24 Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities Through Week 48 Up to Week 48 Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Any Treatment-Emergent Adverse Event Through Week 48 Up to Week 48 Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24 Week 24 The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant'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.
Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 48 Week 48 The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant'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.
Part 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24 Week 24 The percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant'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.
Part 2: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Week 24 Baseline; Week 24 Part 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis at Week 48 Week 48 The percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant'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.
Part 2: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Week 48 Baseline; Week 48 Part 2: Change From Baseline in CD4+ Cell Count at Week 48 Baseline; Week 48 Part 2: Change From Baseline in CD4+ Percentage at Week 48 Baseline; Week 48 Part 2: Change From Baseline in CD4+ Percentage at Week 24 Baseline; Week 24 Part 2: Change From Baseline in CD4+ Cell Count at Week 24 Baseline; Week 24
Trial Locations
- Locations (15)
Regional state budget health agency Krasnoyarsk Regional Center for Prevention and Control of AIDS
🇷🇺Krasnoyarsk, Russian Federation
Midway Immunology and Research center
🇺🇸Fort Pierce, Florida, United States
Joint Clinical Research Centre
🇺🇬Kampala, Uganda
Triple O Research Institute, P.A.
🇺🇸West Palm Beach, Florida, United States
Salvador B Gautier Hospital - Infectious Diseases Department
🇩🇴Santo Domingo, Dominican Republic
Instituto Dominicano de Estudio Virologicos - IDEV
🇩🇴Santo Domingo, Dominican Republic
Penn Presbyterian Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Siriraj Hospital Department of Preventive and Social Medicine, Faculty of Medicine
🇹🇭Bangkok, Thailand
Khon Kaen University
🇹🇭Khon Kaen, Thailand
Ramathibodi Hospital, Mahidol University
🇹🇭Bangkok, Thailand
Chiang Mai University
🇹🇭Chiang Mai, Thailand
The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)
🇹🇭Bangkok, Thailand
Center For Prevention and Treatment of AIDS and Infectious Diseases, Saint Petersburg
🇷🇺Saint Petersburg, Russian Federation
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Rowan Tree Medical, P.A.
🇺🇸Wilton Manors, Florida, United States