Safety and Efficacy of Bictegravir + Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

• ClinicalTrials.gov Identifier: NCT02397694
• Recruitment Status: Completed
• First Posted: March 25, 2015
• Results First Posted: March 27, 2018
• Last Update Posted: April 7, 2020
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Study Description

Brief Summary:

This study will evaluate the efficacy, safety and tolerability of bictegravir (BIC) + emtricitabine/tenofovir alafenamide (F/TAF) fixed dose combination (FDC) versus dolutegravir (DTG) + F/TAF in HIV-1 Infected, antiretroviral treatment-naive adults. This study will also evaluate the pharmacokinetic (PK) profile of BIC, emtricitabine and TAF.

Condition or disease	Intervention/treatment	Phase
HIV-1 Infection	Drug: BIC; Drug: F/TAF; Drug: DTG; Drug: BIC Placebo; Drug: DTG Placebo; Drug: B/F/TAF	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 98 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of GS-9883 + Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected, Antiretroviral Treatment-Naive Adults
• Actual Study Start Date: March 23, 2015
• Actual Primary Completion Date: November 30, 2015
• Actual Study Completion Date: February 27, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: BIC + F/TAF; Participants will receive BIC + F/TAF FDC + DTG placebo for 48 weeks.; Following Week 48, participants will continue to take their blinded treatment and attend visits every 12 weeks until treatment assignments have been unblinded. Participants will return for an unblinding visit and be given the option to participate in an open-label rollover extension and receive bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) until it becomes commercially available, or until Gilead Sciences elects to terminate the development of BIC/F/TAF.	Drug: BIC; 75 mg tablet administered orally once daily; Other Name: GS-9883; Drug: F/TAF; 200/25 mg FDC tablet administered orally once daily; Drug: DTG Placebo; Tablet administered orally once daily; Drug: B/F/TAF; 50/200/25 mg FDC tablet administered orally once daily
Active Comparator: DTG + F/TAF; Participants will receive DTG + F/TAF FDC + BIC placebo for 48 weeks.; Following Week 48, participants will continue to take their blinded treatment and attend visits every 12 weeks until treatment assignments have been unblinded. Participants will return for an unblinding visit and be given the option to participate in an open-label rollover extension and receive B/F/TAF until it becomes commercially available, or until Gilead Sciences elects to terminate the development of BIC/F/TAF.	Drug: F/TAF; 200/25 mg FDC tablet administered orally once daily; Drug: DTG; 50 mg tablet administered orally once daily; Other Name: Tivicay®; Drug: BIC Placebo; Tablet administered orally once daily; Drug: B/F/TAF; 50/200/25 mg FDC tablet administered orally once daily
Experimental: Open Label Extension Phase; After Week 48 participants continued to take their randomized study drug and attended visits every 12 weeks until treatment assignments were unblinded, at which point all participants returned for an unblinding visit and were given the option to participate in an open-label rollover extension to receive an FDC containing B/F/TAF.	Drug: B/F/TAF; 50/200/25 mg FDC tablet administered orally once daily

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With HIV-1 RNA < 50 Copies/mL as Determined by the FDA-defined Snapshot Algorithm. [ Time Frame: Week 24 ]
   The percentage of participants achieving 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.

Secondary Outcome Measures :

1. Percentage of Participants With HIV-1 RNA < 50 Copies/mL as Determined by the FDA-defined Snapshot Algorithm at Week 12 [ Time Frame: Week 12 ]
   The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 12 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.
2. Percentage of Participants With HIV-1 RNA < 50 Copies/mL as Determined by the FDA-defined Snapshot Algorithm at Week 48 [ Time Frame: Week 48 ]
   The percentage of participants achieving 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.
3. The Change From Baseline in log10 HIV-1 RNA at Week 12 [ Time Frame: Baseline; Week 12 ]
4. The Change From Baseline in log10 HIV-1 RNA at Week 24 [ Time Frame: Baseline; Week 24 ]
5. The Change From Baseline in log10 HIV-1 RNA at Week 48 [ Time Frame: Baseline; Week 48 ]
6. The Change From Baseline in Cluster of Differentiation 4 Positive (CD4+) Cell Count at Week 12 [ Time Frame: Baseline; Week 12 ]
7. The Change From Baseline in CD4+ Cell Count at Week 24 [ Time Frame: Baseline; Week 24 ]
8. The Change From Baseline in CD4+ Cell Count at Week 48 [ Time Frame: Baseline; Week 48 ]
9. Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) During Double-Blinded Randomized Phase [ Time Frame: First dose date up to last dose (maximum duration: 58 Weeks) plus 30 days (During Double-Blinded Randomized Phase) ]
10. Percentage of Participants With Treatment Emergent Laboratory Abnormalities During Double-Blind Randomized Phase [ Time Frame: First dose date up to last dose (maximum duration: 58 Weeks) plus 30 days (During Double-Blinded Randomized Phase) ]
11. PK Parameter: Cmax for Bictegravir (BIC), Emtricitabine (FTC), Tenofovir Alafenamide (TAF) and Tenofavir (TFV) at Steady-State [ Time Frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8 ]
    Cmax is the maximum observed plasma concentration of the drug.
12. PK Parameter: Tmax for BIC, FTC, TAF, and TFV at Steady-State [ Time Frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8 ]
    Tmax was defined as the time to Cmax.
13. PK Parameter:Ctau for BIC, FTC and TFV [ Time Frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8 ]
    Ctau was defined as the observed drug concentration at the end of the dosing interval.
14. PK Parameter: AUCtau for BIC, FTC, TAF, and TFV [ Time Frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8 ]
    AUCtau is defined as the area under the concentration-time curve of the drug over time.
15. PK Parameter: t1/2 of BIC, FTC, TAF, and TFV [ Time Frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8 ]
    t1/2 was defined as the terminal elimination half-life of the drug

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• Antiretroviral naive (≤ 10 days of prior therapy with any antiretroviral agent)
• Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening
• Screening genotype report provided by Gilead Sciences must show sensitivity to tenofovir (TFV) and emtricitabine (FTC)
• Adequate renal function as measured by estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft-Gault formula
• CD4+ cell count ≥ 200 cells/µL at screening

Key Exclusion Criteria:

• A new AIDS-defining condition diagnosed within the 30 days prior to screening as defined in the study protocol
• Prior use of antiretrovirals in the setting of pre-exposure prophylaxis (PrEP) or post exposure prophylaxis (PEP)
• Chronic hepatitis B virus (HBV) infection
• Hepatitis C infection (Individuals who are hepatitis C virus (HCV) Ab positive, but have a documented negative HCV RNA, are eligible)
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
• Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial

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

Contacts and Locations

Locations

United States, Arizona

Phoenix, Arizona, United States, 85012

United States, California

Los Angeles, California, United States, 90036

Los Angeles, California, United States, 90069

Sacramento, California, United States, 95817

United States, District of Columbia

Washington, District of Columbia, United States, 20009

Washington, District of Columbia, United States, 20036

United States, Florida

Fort Lauderdale, Florida, United States, 33316

Orlando, Florida, United States, 32803

West Palm Beach, Florida, United States, 33401

United States, Georgia

Atlanta, Georgia, United States, 30312

Decatur, Georgia, United States, 30033

United States, Massachusetts

Boston, Massachusetts, United States, 02115

United States, Michigan

Berkley, Michigan, United States, 48072

United States, New Jersey

Newark, New Jersey, United States, 07102

United States, Texas

Austin, Texas, United States, 78705

Dallas, Texas, United States, 75208

Houston, Texas, United States, 77004

Houston, Texas, United States, 77098

Longview, Texas, United States, 75605

United States, Virginia

Annandale, Virginia, United States, 22003

United States, Washington

Seattle, Washington, United States, 98104

Sponsors and Collaborators

Gilead Sciences

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

More Information

Publications of Results:

Sax PE, DeJesus E, Crofoot G, Ward D, Benson P, Dretler R, Mills A, Brinson C, Peloquin J, Wei X, White K, Cheng A, Martin H, Quirk E. Bictegravir versus dolutegravir, each with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection: a randomised, double-blind, phase 2 trial. Lancet HIV. 2017 Apr;4(4):e154-e160. doi: 10.1016/S2352-3018(17)30016-4. Epub 2017 Feb 15.

Sax PE, DeJesus E, Crofoot G, Ward D, Benson P, Dretler R, Mills A, Brinson C, Wei X, Collins SE, Cheng A. Coformulated bictegravir, emtricitabine, tenofovir alafenamide after initial treatment with bictegravir or dolutegravir and emtricitabine/tenofovir alafenamide. AIDS. 2018 Jul 31;32(12):1723-1725. doi: 10.1097/QAD.0000000000001894.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02397694
• Other Study ID Numbers: GS-US-141-1475
• First Posted: March 25, 2015
• Results First Posted: March 27, 2018
• Last Update Posted: April 7, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gilead Sciences:

Adult; HIV; naive

Additional relevant MeSH terms:

Dolutegravir; HIV Integrase Inhibitors; Integrase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents