Clinical trial NCT02603107: Study to Evaluate the Safety and Efficacy of Switching From Regimens Consisting of Boosted Atazanavir or Darunavir Plus Either Emtricitabine/Tenofovir or Abacavir/Lamivudine to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-1 Infected Adults
Official title: A Phase 3, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Switching From Regimens Consisting of Boosted Atazanavir or Darunavir Plus Either Emtricitabine/Tenofovir or Abacavir/Lamivudine to GS-9883/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-1 Infected Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-11-11
Enrollment: 578
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the efficacy of switching to a fixed-dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing on a regimen consisting of boosted atazanavir (ATV) or darunavir (DRV) plus either emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) in HIV-1 infected adults who are virologically suppressed.


Eligibility criteria: Key Inclusion Criteria:

* Currently receiving a once daily antiretroviral regimen consisting of ritonavir or cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC for ≥ 6 months preceding the screening visit
* Adequate renal function:

  * Estimated glomerular filtration rate ≥ 50 mL/min (≥ 0.83 mL/sec) according to the Cockcroft-Gault formula
* Life expectancy ≥ 1 year
* Currently on a stable regimen for ≥ 6 months preceding the screening visit with documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 6 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Prior changes in antiretroviral regimen are only allowed due to tolerability issues or for regimen simplification. Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable. (If the lower limit of detection of the local HIV-1 RNA assay is \< 50 copies/mL \[e.g., \< 20 copies/mL\], the plasma HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests)
* Have no documented or suspected resistance to FTC, tenofovir, ABC or 3TC, including but not limited to the reverse transcriptase resistance mutations K65R and M184V/I
* No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI)

Key Exclusion Criteria:

* An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening
* Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or variceal bleeding)
* Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine based therapies)
* Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
* A history of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Individuals with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Day 1 and are not 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 Day 1
* Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial
* Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with the dosing requirements
* Any known allergies to the excipients of B/F/TAF FDC or ATV, RTV, DRV, COBI, FTC/TDF or ABC/3TC
* Females who are pregnant (as confirmed by positive serum pregnancy test)
* Females who are breastfeeding
* Acute hepatitis in the 30 days prior to study entry
* Chronic hepatitis B infection in individuals not on a TDF containing regimen, as determined by either:

  * Positive hepatitis B virus (HBV) surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit
  * Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit
* Active tuberculosis infection

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm
timeFrame: Week 48
measure: Change From Baseline in CD4 Cell Count at Week 48
timeFrame: Baseline to Week 48
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Newport Beach
country: United States
state: California
city: Oakland
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: San Leandro
country: United States
state: California
city: Torrance
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Washington
country: United States
state: District of Columbia
city: DeLand
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Fort Pierce
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Pensacola
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Vero Beach
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Wilton Manors
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Augusta
country: United States
state: Georgia
city: Macon
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Chicago
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Kansas City
country: United States
state: Kansas
city: Louisville
country: United States
state: Kentucky
city: New Orleans
country: United States
state: Louisiana
city: Boston
country: United States
state: Massachusetts
city: Springfield
country: United States
state: Massachusetts
city: Berkley
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Bronx
country: United States
state: New York
city: Bronx
country: United States
state: New York
city: Buffalo
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Greenville
country: United States
state: North Carolina
city: Huntersville
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Columbia
country: United States
state: South Carolina
city: Memphis
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Longview
country: United States
state: Texas
city: Annandale
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Darlinghurst
country: Australia
state: New South Wales
city: Sydney
country: Australia
state: New South Wales
city: Fitzroy
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Prahran
country: Australia
state: Victoria
city: Brussels
country: Belgium
city: Ghent
country: Belgium
city: Vancouver
country: Canada
state: British Columbia
city: Toronto
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Santo Domingo
country: Dominican Republic
city: Lyon
country: France
city: Nantes
country: France
city: Nice
country: France
city: Paris
country: France
city: Paris
country: France
city: Tourcoing
country: France
city: Tours
country: France
city: Düsseldorf
country: Germany
state: Nordrhein-Westfalen
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Bonn
country: Germany
city: Essen
country: Germany
city: Frankfurt
country: Germany
city: Frankfurt
country: Germany
city: Hamburg
country: Germany
city: Köln
country: Germany
city: Munchen
country: Germany
city: München
country: Germany
city: Milano
country: Italy
city: Milano
country: Italy
city: Roma
country: Italy
city: Ponce
country: Puerto Rico
city: Rio Piedras
country: Puerto Rico
city: San Juan
country: Puerto Rico
city: San Juan
country: Puerto Rico
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Málaga
country: Spain
city: Birmingham
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Brighton
country: United Kingdom
city: Edinburgh
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Daar ES, DeJesus E, Ruane P, Crofoot G, Oguchi G, Creticos C, Rockstroh JK, Molina JM, Koenig E, Liu YP, Custodio J, Andreatta K, Graham H, Cheng A, Martin H, Quirk E. Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2018 Jul;5(7):e347-e356. doi: 10.1016/S2352-3018(18)30091-2. Epub 2018 Jun 18.
citation: Andreatta K, Willkom M, Martin R, Chang S, Wei L, Liu H, Liu YP, Graham H, Quirk E, Martin H, White KL. Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. J Antimicrob Chemother. 2019 Dec 1;74(12):3555-3564. doi: 10.1093/jac/dkz347.