Overview

This trial is active, not recruiting.

Conditions hiv, hiv infections, acquired immunodeficiency syndrome
Treatments taf, placebo to match taf, e/c/f/taf, pre-existing arv regimen, atv
Phase phase 3
Sponsor Gilead Sciences
Start date August 2013
End date May 2016
Trial size 55 participants
Trial identifier NCT01967940, 2013-002830-19, GS-US-292-0117

Summary

Part 1 consists of 2 cohorts, starting with a sentinel cohort, in which 10 participants will be enrolled to receive open-label tenofovir alafenamide (TAF) in addition to their current failing antiretroviral (ARV) regimen. This cohort will then be followed by a randomized, double-blind, cohort to compare the addition of TAF or placebo-to-match TAF in HIV-1 positive adults who are failing their current ARV regimen. This randomized cohort will consist of approximately 90 participants.

In Part 2, all participants who complete Part 1 of the study will discontinue their failing ARV regimen and TAF or placebo-to-match TAF 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 single-tablet regimen (E/C/F/TAF 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Participants will be randomized to receive TAF plus their pre-existing ARV regimen for 10 days in Part 1, followed by a 14-day washout period. After this period, participants with a > 0.5 log10 decline in HIV-1 RNA will then receive E/C/F/TAF plus ATV for 48 weeks in Part 2.
taf
Tenofovir alafenamide (TAF) 25 mg tablet administered orally once daily with food
e/c/f/taf Genvoya®
Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (E/C/F/TAF) single-tablet regiment (STR) administered orally once daily with food
pre-existing arv regimen
Participants will continue taking their pre-existing ARV regimen as prescribed in Part 1.
atv
ATV 300 mg tablet administered orally once daily.
(Experimental)
Participants will receive placebo to match TAF plus their pre-existing ARV regimen for 10 days in Part 1, followed by a 14-day washout period, and then receive E/C/F/TAF plus ATV for 48 weeks in Part 2 regardless of HIV-1 RNA value.
placebo to match taf
Placebo tablets to match TAF administered orally once daily with food
e/c/f/taf Genvoya®
Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (E/C/F/TAF) single-tablet regiment (STR) administered orally once daily with food
pre-existing arv regimen
Participants will continue taking their pre-existing ARV regimen as prescribed in Part 1.
atv
ATV 300 mg tablet administered orally once daily.

Primary Outcomes

Measure
Proportion of participants with plasma HIV-1 RNA decreases from baseline exceeding 0.5 log10 copies/mL at Day 10 (Part 1)
time frame: Day 10

Secondary Outcomes

Measure
Change from baseline in plasma HIV-1 RNA (log10 copies/mL) at Day 10 (Part 1)
time frame: Day 10
Percentage of participants with plasma HIV-1 RNA < 50 copies/mL
time frame: Weeks 24 and 48
Percentage of participants with plasma HIV-1 RNA < 400 copies/mL
time frame: Weeks 24 and 48
Change from baseline in plasma HIV-1 RNA (log10 copies/mL)
time frame: Weeks 24 and 48
Change from baseline in CD4+ cell count (cells/µL) and percentage
time frame: Weeks 24 and 48
Safety of E/C/F/TAF STR plus ATV measured by incidence of adverse events and monitoring of laboratory parameters from baseline to Weeks 24 and 48
time frame: Baseline to Week 24 and 48
Plasma pharmacokinetics (PK) parameter of TAF as measured by AUClast, Clast, and Cmax and PK parameter of tenofovir, ATV, and elvitegravir as measured by AUCtau, Ctau, and Cmax
time frame: Week 4 to Week 12

Eligibility Criteria

Male or female participants at least 18 years old.

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 - Screening or historical genotype report showing either 1 to 3 thymidine-analogue mutations (TAMs) and/or K65R, as well as M184V/I - 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 (Subjects with positive 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

Additional Information

Official title A Phase 3, Two Part Study to Evaluate the 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
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by Gilead Sciences.