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

HIV-1 Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02603107
• Other study ID #: GS-US-380-1878
• Secondary ID: 2015-004011-20
• Status: Completed
• Phase: Phase 3
• Start date: November 20, 2015
• Est. completion date: December 23, 2019

Study information

• Verified date: December 2020
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 578
• Est. completion date: December 23, 2019
• Est. primary completion date: May 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• RTV
100 mg capsule coadministered orally with ATV or DRV once daily with food
• ATV
300 mg capsule administered orally once daily with food
• DRV
800 mg tablet administered orally once daily with food
• COBI
150 mg tablet coadministered orally with ATV or DRV once daily with food
• ATV/co
300/150 mg FDC tablet administered orally once daily with food
• DRV/co
800/150 mg FDC tablet administered orally once daily with food
• FTC/TDF
200/300 mg FDC tablet administered orally once daily without regard to food
• ABC/3TC
600/300 mg tablet administered orally once daily with or without regard to food
• B/F/TAF
50/200/25 mg FDC tablet administered orally once daily without regard to food

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Dominican Republic,  France,  Germany,  Italy,  Puerto Rico,  Spain,  United Kingdom, 

References & Publications (2)

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 i — View 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 tenofovi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With HIV-1 RNA = 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm	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.	Week 48
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm	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.	Week 48
Secondary	Change From Baseline in CD4 Cell Count at Week 48		Baseline to Week 48