Study to Evaluate the Safety and Efficacy of Bictegravir/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Alafenamide in Human Immunodeficiency Virus (HIV-1) Infected, Antiretroviral Treatment-Naive Adults

HIV-1 Infection Clinical Trial

Official title:

A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02607956
• Other study ID #: GS-US-380-1490
• Secondary ID: 2015-003988-10
• Status: Completed
• Phase: Phase 3
• Start date: November 11, 2015
• Est. completion date: July 5, 2021

Study information

• Verified date: February 2022
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This primary objective of this study is to evaluate the efficacy of a fixed dose combination (FDC) containing bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus dolutegravir (DTG) + a FDC containing emtricitabine/tenofovir alafenamide (F/TAF) in HIV-1 infected, antiretroviral treatment-naive adults.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 657
• Est. completion date: July 5, 2021
• Est. primary completion date: May 12, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Antiretroviral treatment naive (= 10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection) except the use for pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), up to one month prior to screening
• Plasma HIV-1 ribonucleic acid (RNA) levels = 500 copies per milliliter (mL) at screening
• Adequate renal function: Estimated glomerular filtration rate = 30 mL per minute (min) (= 0.50 mL per second (sec)) according to the Cockcroft-Gault formula

Key Exclusion Criteria:

• An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening
• Decompensated cirrhosis (eg, ascites, encephalopathy, or variceal bleeding)
• Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
• Females who are pregnant (as confirmed by positive serum pregnancy test)
• Females who are breastfeeding Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• DTG
50 mg tablets administered orally, once daily
• F/TAF
200/25 mg tablets administered orally, once daily
• B/F/TAF
50/200/25 milligrams (mg) FDC tablets administered orally, once daily
• DTG Placebo
Tablets administered orally, once daily
• F/TAF Placebo
Tablets administered orally, once daily
• B/F/TAF Placebo
Tablets administered orally, once daily

Locations

Country	Name	City	State
Australia	Prahran Market Clinic	Prahran	Victoria
Canada	McGill University Health Center	Montreal
Canada	Sunnybrook Health Sciences Centre	Toronto
France	CHU de Nice Archet I	Nice
Germany	Uniklinik Köln	Köln
Spain	Hospital Universitario Ramon y Cajal	Madrid
United Kingdom	Chelsea and Westminster NHS Trust	London
United Kingdom	St George's Healthcare NHS Trust	London
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	AIDS Arms Inc	Dallas	Texas
United States	North Texas Infectious Diseases Consultants PA	Dallas	Texas
United States	Cone Health Regional Center for Infectious Disease	Greensboro	North Carolina
United States	Allegheny Health Network	Pittsburgh	Pennsylvania
United States	Optimus Medical - ClinEdge - PPDS	San Francisco	California
United States	Kaiser Permanente	San Leandro	California

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 (24)

Acosta R, Andreatta K, D'Antoni M, Collins S, Martin H, White K. Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) shows high efficacy in clinical study participants infected with HIV-1 subtype F. [Poster P124]. HIV Drug Therapy 2020 (HIV Glasgow

Acosta R, Andreatta K, D'Antoni M, Collins S, Martin H, White K. HIV Viral Blips in Adults Treated with INSTI-Based Regimens Through 144 Weeks. [Poster 540]. Conference on Retroviruses and Opportunistic Infections 2020 (CROI 2020); 2020 March 8-11; Boston

Acosta R, Chen G, Chang S, Martin R, Wang X, Huang H, et al. HIV with Transmitted Drug Resistance Is Durably Suppressed by B/F/TAF at Week 144. [Poster 430]. Conference on Retroviruses and Opportunistic Infections 2021 (CROI 2021); 2021 June 3-November 3;

Acosta R, Chen G, Huang H, Liu H, White K. Unreturned Pill Bottles in the 1489 and 1490 Clinical Trials: An Important Measure of Poor Adherence That Is Often Ignored in Pill Count Calculations. [Poster 902]. IDWeek 2021; 2021 September 29-October 3; Virtu

Acosta R, Chen G, Qin L, Wang X, Huang H, Hindman J, et al. Achievement of Undetectable HIV-1 RNA in the B/F/TAF Treatment-Naive Clinical Trials. [Poster PEB150]. 11th IAS Conference on HIV Science (IAS 2021); 2021 July 18-21; Virtual.

Acosta R, White K, Garner W, Wei X, Andreatta K, Willkom M, et al. HIV-1 subtype (B or non-B) had no impact on the efficacy of B/F/TAF or resistance development in five phase 3 treatment-naïve or switch studies. [Poster THPEB077]. 22nd International AIDS

Acosta R, Willkom M, Martin R, Chang S, Liu X, Hedskog C, et al. Low-frequency resistance variants in ART-naive participants do not affect bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) triple therapy outcome. [Poster MOPEB242]. 10th IAS Confer

Acosta RK, Chen GQ, Chang S, Martin R, Wang X, Huang H, Brainard D, Collins SE, Martin H, White KL. Three-year study of pre-existing drug resistance substitutions and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in HIV-1 treatment-naive par — View Citation

Acosta RK, Willkom M, Martin R, Chang S, Wei X, Garner W, Lutz J, Majeed S, SenGupta D, Martin H, Quirk E, White KL. Resistance Analysis of Bictegravir-Emtricitabine-Tenofovir Alafenamide in HIV-1 Treatment-Naive Patients through 48 Weeks. Antimicrob Agen — View Citation

Arribas J, Orkin C, Maggiolo F, Antinori A, Lazzarin A, Yasdanpanah, et al. Long-term Analysis of B/F/TAF in Treatment-Naïve Adults Living With HIV Through Four Years of Follow-up. [PEB151]. 11th IAS Conference on HIV Science (IAS 2021); 2021 July 18-21;

Daar E, Orkin C, Sax P, Stephens J, Koenig E, Clarke A, et al. Incidence of Metabolic Complications Among Treatment-naïve Adults Living With HIV-1 Randomized to B/F/TAF, DTG/ABC/3TC or DTG+F/TAF After 3 Years. [Oral 69]. IDWeek 2021; 2021 September 29- Oc

Gupta S, Mills A, Brinson C, Workowski K, Clarke A, Antinori A, et al. 96 Week Efficacy and Safety of B/F/TAF in Treatment-Naïve Adults and Adults =50 Years [Poster 502]. CROI 2019; 2019 04-07 March; Seattle, WA.

Gupta SK, Post FA, Arribas JR, Eron JJ Jr, Wohl DA, Clarke AE, Sax PE, Stellbrink HJ, Esser S, Pozniak AL, Podzamczer D, Waters L, Orkin C, Rockstroh JK, Mudrikova T, Negredo E, Elion RA, Guo S, Zhong L, Carter C, Martin H, Brainard D, SenGupta D, Das M. — View Citation

Johnson M, Taylor S, Wei X, Collins SE, Martin H. Hepatic Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide [Poster P061]. 25th Annual Conference of the British HIV Association; 2019 02-05 April; Bournemouth, United Kingdom.

Mills A, Gupta SK, Brinson C, Workowski K, Clarke A, Antinori A, Stephens JL, et al. 144-Week Efficacy and Safety of B/F/TAF in Treatment-Naive Adults Age =50 Years. [Poster 477]. Conference on Retroviruses and Opportunistic Infections 2020 (CROI 2020); 2

Orkin C, DeJesus E, Sax PE, Arribas JR, Gupta SK, Martorell C, Stephens JL, Stellbrink HJ, Wohl D, Maggiolo F, Thompson MA, Podzamczer D, Hagins D, Flamm JA, Brinson C, Clarke A, Huang H, Acosta R, Brainard DM, Collins SE, Martin H; GS-US-380-1489; GS-US- — View Citation

Pozniak A, et al. Outcomes 48 Weeks After Switching From DTG/ABC/3TC or DTG+F/TAF to B/F/TAF. [PE2/68]. 18th European AIDS Conference (EAC 2021), 2021 October 27-30; London, United Kingdom.

Ramgopal M, Maggiolo F, Ward D, Leboucche B, Rizzardini G, Molina JM, et al. Pooled Analysis of 4 International Trials of Bictegravir/Emtrictabine/Tenofovir Alafenamide (B/F/TAF) in Adults Aged = 65 Years Demonstrating Safety and Efficacy: Week 48 Results

Sax PE, Pozniak A, Montes ML, Koenig E, DeJesus E, Stellbrink HJ, Antinori A, Workowski K, Slim J, Reynes J, Garner W, Custodio J, White K, SenGupta D, Cheng A, Quirk E. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravi — View Citation

Stellbrink HJ, Arribas JR, Stephens JL, Albrecht H, Sax PE, Maggiolo F, Creticos C, Martorell CT, Wei X, Acosta R, Collins SE, Brainard D, Martin H. Co-formulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine — View Citation

White K, Kulkarni R, Willkom M, Martin R, Chang S, Wei X, et al. Pooled week 48 efficacy and baseline resistance: B/F/TAF in treatment-naive patients. [Poster 532]. Conference on Retroviruses and Opportunistic Infections; 2018 March 4-7; Boston, USA.

Wohl D, Clarke A, Maggiolo F, Garner W, Laouri M, Martin H, Quirk E. Patient-Reported Symptoms Over 48 Weeks Among Participants in Randomized, Double-Blind, Phase III Non-inferiority Trials of Adults with HIV on Co-formulated Bictegravir, Emtricitabine, a — View Citation

Wohl DA, Yazdanpanah Y, Baumgarten A, Clarke A, Thompson MA, Brinson C, Hagins D, Ramgopal MN, Antinori A, Wei X, Acosta R, Collins SE, Brainard D, Martin H. Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, — View Citation

Workowski K, Orkin C, Sax P, Hagins D, Koenig E, Stephens JL, et al. Four-Year Outcomes of B/F/TAF in Treatment-Naïve Adults [Poster 415]. Conference on Retroviruses and Opportunistic Infections 2021 (CROI 2021); 2021 June 3-November 3; Virtual.

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm	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
Secondary	Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 96 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 96
Secondary	Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 144 as Defined by the US FDA-Defined Snapshot Algorithm	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 144 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 144
Secondary	Percentage of Participants Who Achieved HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm	The percentage of participants achieving HIV-1 RNA < 20 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 Who Achieved HIV-1 RNA < 20 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm	The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 96 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 96
Secondary	Percentage of Participants Who Achieved HIV-1 RNA < 20 Copies/mL at Week 144 as Defined by the US FDA-Defined Snapshot Algorithm	The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 144 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 144
Secondary	Change From Baseline in log10 HIV-1 RNA at Week 48		Baseline, Week 48
Secondary	Change From Baseline in log10 HIV-1 RNA at Week 96		Baseline, Week 96
Secondary	Change From Baseline in log10 HIV-1 RNA at Week 144		Baseline, Week 144
Secondary	Change From Baseline in CD4+ Cell Count at Week 48		Baseline, Week 48
Secondary	Change From Baseline in CD4+ Cell Count at Week 96		Baseline, Week 96
Secondary	Change From Baseline in CD4+ Cell Count at Week 144		Baseline, Week 144
Secondary	Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 Open-Label as Defined by Missing = Excluded Algorithm	The percentage of participants with HIV-1 RNA < 50 copies/mL was analyzed using Missing = Excluded for imputing missing HIV-1 RNA values using the All B/F/TAF Analysis Set for the all B/F/TAF analysis. All missing data was excluded in the computation of the percentages (ie, missing data points were excluded from both the numerator and denominator in the computation). The denominator for percentages at a visit was the number of participants in the all B/F/TAF analysis set with nonmissing HIV-1 RNA value at that visit.	Baseline, open-label Week 48
Secondary	Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 Open-Label as Defined by Missing = Failure Algorithm	The percentage of participants with HIV-1 RNA < 50 copies/mL was analyzed using Missing = Failure for imputing missing HIV-1 RNA values using the All B/F/TAF Analysis Set for the all B/F/TAF analysis. All missing data was treated as HIV-1 RNA = 50 copies/mL. The denominator for percentages was the number of participants in all B/F/TAF analysis set.	Baseline, open-label Week 48
Secondary	Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 Open-Label as Defined by Missing = Excluded Algorithm	The percentage of participants with HIV-1 RNA < 50 copies/mL was analyzed using Missing = Excluded for imputing missing HIV-1 RNA values using the All B/F/TAF Analysis Set for the all B/F/TAF analysis. All missing data was excluded in the computation of the percentages (ie, missing data points were excluded from both the numerator and denominator in the computation). The denominator for percentages at a visit was the number of participants in the all B/F/TAF analysis set with nonmissing HIV-1 RNA value at that visit.	Baseline, open-label Week 96
Secondary	Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 Open-Label as Defined by Missing = Failure Algorithm	The percentage of participants with HIV-1 RNA < 50 copies/mL was analyzed using Missing = Failure for imputing missing HIV-1 RNA values using the All B/F/TAF Analysis Set for the all B/F/TAF analysis. All missing data was treated as HIV-1 RNA = 50 copies/mL. The denominator for percentages was the number of participants in all B/F/TAF analysis set.	Baseline, open-label Week 96
Secondary	Change From Baseline in CD4+ Cell Count at Week 48 Open-Label		Baseline, open-label Week 48
Secondary	Change From Baseline in CD4+ Cell Count at Week 96 Open-Label		Baseline, open-label Week 96