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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: BIC; Drug: F/TAF; Drug: DTG Placebo; Drug: B/F/TAF; Drug: DTG; Drug: BIC Placebo

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
  • California
    • Los Angeles, California, United States, 90036
    • Los Angeles, California, United States, 90069
    • Sacramento, California, United States, 95817
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
    • Washington, District of Columbia, United States, 20036
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
    • Orlando, Florida, United States, 32803
    • West Palm Beach, Florida, United States, 33401
  • Georgia
    • Atlanta, Georgia, United States, 30312
    • Decatur, Georgia, United States, 30033
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
  • Michigan
    • Berkley, Michigan, United States, 48072
  • New Jersey
    • Newark, New Jersey, United States, 07102
  • 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
  • Virginia
    • Annandale, Virginia, United States, 22003
  • Washington
    • Seattle, Washington, United States, 98104

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / 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 Names: 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: B/F/TAF; 50/200/25 mg FDC tablet administered orally once daily; Drug: DTG; 50 mg tablet administered orally once daily; Other Names: Tivicay®; Drug: BIC Placebo; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA < 50 Copies/mL as Determined by the FDA-defined Snapshot Algorithm.	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.	Week 24

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2015
• Primary Completion (Actual): November 30, 2015
• Study Completion (Actual): February 27, 2019

Study Registration Dates

• First Submitted: March 20, 2015
• First Submitted That Met QC Criteria: March 20, 2015
• First Posted (Estimate): March 25, 2015

Study Record Updates

• Last Update Posted (Actual): April 7, 2020
• Last Update Submitted That Met QC Criteria: March 25, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: HIV; Adult; naive
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Dolutegravir
• Other Study ID Numbers: GS-US-141-1475

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No