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

NCT ID: NCT01967940

Last Updated: 2018-11-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-25
• Study Completion Date: 2017-07-31

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.

Conditions

HIV; HIV Infections; Acquired Immunodeficiency Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part 1 Sentinel Cohort (TAF)

TAF + their current failing ARV regimen for 10 days in Part 1

Group Type: EXPERIMENTAL

TAF

Intervention Type: DRUG

25 mg tablet administered orally once daily with food

Current failing ARV regimen

Intervention Type: DRUG

Participants will continue taking their current ARV regimen as prescribed in Part 1.

Part 1 Randomized Cohort (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.

Group Type: EXPERIMENTAL

TAF

Intervention Type: DRUG

25 mg tablet administered orally once daily with food

Current failing ARV regimen

Intervention Type: DRUG

Participants will continue taking their current ARV regimen as prescribed in Part 1.

Part 1 Randomized Cohort (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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Tablets to match TAF administered orally once daily with food

Current failing ARV regimen

Intervention Type: DRUG

Participants will continue taking their current ARV regimen as prescribed in Part 1.

Part 2 E/C/F/TAF+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.

Group Type: EXPERIMENTAL

E/C/F/TAF

Intervention Type: DRUG

150/150/200/10 mg STR administered orally once daily with food

ATV

Intervention Type: DRUG

300 mg tablet administered orally once daily.

Interventions

TAF

25 mg tablet administered orally once daily with food

Intervention Type: DRUG

Placebo

Tablets to match TAF administered orally once daily with food

Intervention Type: DRUG

E/C/F/TAF

150/150/200/10 mg STR administered orally once daily with food

Intervention Type: DRUG

Current failing ARV regimen

Participants will continue taking their current ARV regimen as prescribed in Part 1.

Intervention Type: DRUG

ATV

300 mg tablet administered orally once daily.

Intervention Type: DRUG

Other Intervention Names

Vemlidy®; GS-7340; Genvoya®; Reyataz®

Eligibility Criteria

Inclusion Criteria

• Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
• Currently taking a failing ARV regimen
• Plasma HIV-1 RNA ≥ 500 copies/mL but ≤ 100,000 copies/mL at screening
• Normal ECG
• Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
• Alanine aminotransferase (AST)/aspartate aminotransferase (AST) ≤ 5 × the upper limit of the normal range (ULN)
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
• Adequate hematologic function
• Serum amylase ≤ 5 × ULN
• Females may enter the study if it is confirmed that she is:

• Not pregnant or nursing
• 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
• 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.
• 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.
• Males must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Midway Immunology and Research center

Ft. Pierce, Florida, United States

Triple O Research Institute, P.A.

West Palm Beach, Florida, United States

Rowan Tree Medical, P.A.

Wilton Manors, Florida, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

Salvador B Gautier Hospital - Infectious Diseases Department

Santo Domingo, , Dominican Republic

Instituto Dominicano de Estudio Virologicos - IDEV

Santo Domingo, , Dominican Republic

Regional state budget health agency Krasnoyarsk Regional Center for Prevention and Control of AIDS

Krasnoyarsk, , Russia

Center For Prevention and Treatment of AIDS and Infectious Diseases, Saint Petersburg

Saint Petersburg, , Russia

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)

Bangkok, , Thailand

Ramathibodi Hospital, Mahidol University

Bangkok, , Thailand

Siriraj Hospital Department of Preventive and Social Medicine, Faculty of Medicine

Bangkok, , Thailand

Chiang Mai University

Chiang Mai, , Thailand

Khon Kaen University

Khon Kaen, , Thailand

Joint Clinical Research Centre

Kampala, , Uganda

Countries

United States; Dominican Republic; Russia; Thailand; Uganda

Other Identifiers

2013-002830-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-292-0117

Identifier Type: -

Identifier Source: org_study_id