A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Switching From a Regimen of Dolutegravir and ABC/3TC, or a Fixed Dose Combination (FDC) of ABC/DTG/3TC to a FDC of GS-9883/F/TAF in HIV-1 Infected Subjects Who Are Virologically Suppressed

At a glance

Drugs Bictegravir/emtricitabine/tenofovir alafenamide (Primary) ; Abacavir/dolutegravir/lamivudine
Indications HIV-1 infections
Focus Registrational; Therapeutic Use
Sponsors Gilead Sciences

Most Recent Events

10 Dec 2021 Results of pooled analysis (n=1906) assessing virologic outcomes through 48 weeks of B/F/TAF treatment in individuals with pre-existing primary INSTI-R from 7 bictegravir/emtricitabine/tenofovir alafenamide studies (GS-US-380-1489/NCT02607930 and GS-US-380-1490/NCT02607956), (GS-US-380-1844/NCT02603120; GS-US-380-1878/NCT02603107; GS-US-380-4580/NCT03631732; GS-US-380-4030/NCT03110380 and GS-US-380-4449/NCT03405935), published in the JAIDS.
30 Oct 2021 Results (n=2079) of pooled analysis assessing the safety and efficacy of switching adults with suppressed HIV to bictegravir/emtricitabine/tenofo - vir alafenamide (B/F/TAF) from 5 studies (Studies 1844, 1878, 4030, 4449, and 4580) presented at the 18th European AIDS Conference
21 Jul 2021 Results assessimg long-term efficacy in patients who switched to bictegravir/emtricitabinetTenofovir alafenamide from DTG/ABC/3TC with preexisting resistance and viral blips, presented at the 11th International AIDS Society Conference on HIV Science

Trial Overview

Outcome

Primary endpoint met - positive

Purpose

This phase III study is designed to evaluate the efficacy of switching from a regimen of dolutegravir (DTG) and abacavir/lamivudine (ABC/3TC) or a fixed dose combination (FDC) of abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) to a FDC of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing DTG and ABC/3TC as the FDC ABC/DTG/3TC in virologically suppressed HIV-1 infected adults.

Comments

According to a Gilead Sciences media release, Biktarvy (bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg, BIC/FTC/TAF), has been approved in China for the treatment of HIV-1 infection, based on the results of 4 trials (1489, 1490, 1844 and 1878).

In March 2019, the Japan's Ministry of Health, Labour and Welfare (MHLW) has approved Biktarvy (bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg, BIC/FTC/TAF), a once-daily single tablet regimen (STR) for the treatment of HIV-1 infection.
In 2018, the drug has also been approved by the Hong Kong Department of Health, the U.S. Food and Drug Administration (FDA) and the European Commission.
The approval of Biktarvy is supported by data from four Phase 3 studies (Studies 1489, 1490, 1844 and 1878).

Primary Endpoints

Met on 30 May 2017

Proportion of participants with virologic failure (HIV-1 RNA ≥ 50 copies/mL) as defined by the modified US FDA snapshot algorithm

safety_issue: No
time_frame: Week 48^[1]

Other Endpoints

Percentage of Participants With HIV-1 RNA < 50 Copies/mL as Defined by the US FDA-defined Snapshot Algorithm

description: 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.
time_frame: Week 48

Change From Baseline in CD4+ Cell Count at Week 48

time_frame: Baseline; Week 48

Spine Bone Mineral Density (BMD) at Baseline

time_frame: Baseline

Percentage Change From Baseline in Spine BMD at Week 48

time_frame: Baseline; Week 48

Hip Bone Mineral Density at Baseline

time_frame: Baseline

Percentage Change From Baseline in Hip BMD at Week 48

time_frame: Baseline; Week 48^[2]

Diseases Treated

Indication	Qualifiers	Patient Segments
HIV-1 infections	treatment	-

Biomarker

NCT Number	Biomarker Name	Biomarker Function
NCT02603120		T-cell surface antigen CD4	Outcome Measure

For more detail, check out BiomarkerBase: the leading source of information about biomarkers used in drug development and diagnostic tests, tracking a comprehensive list of biomarker uses worldwide by over 800 companies

Subjects

Subject Type patients
Number
Planned: 520

Actual: 563
Sex male & female
Age Group ≥ 18 years; adult; elderly

Patient Inclusion Criteria

Key - Estimated glomerular filtration rate ≥ 50 mL/min (≥ 0.83 mL/sec). - Currently receiving an antiretroviral regimen of DTG + ABC/3TC, or ABC/DTG/3TC FDC for ≥ 3 months prior to the screening visit. - HIV ribonucleic acid (RNA) < 50 copies/mL at the screening visit. - Currently on a stable regimen for ≥ 3 months preceding the screening visit with documented plasma HIV-1 RNA < 50 copies/mL for ≥ 3 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). - Have no documented or suspected resistance to emtricitabine (FTC), tenofovir (TFV), DTG, ABC or 3TC. Key

Patient Exclusion Criteria

- Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance. - Active tuberculosis infection. - Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or variceal bleeding). - Females who are pregnant. - Females who are breastfeeding. - Acute hepatitis in the 30 days prior to study entry. - Chronic Hepatitis B Virus (HBV) infection. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial Details

Identifiers

Identifier	Owner
NCT02603120	ClinicalTrials.gov: US National Institutes of Health
EudraCT2015-004025-14	European Clinical Trials Database
GS-US380-1844	Gilead Sciences
Study 1844	-

Organisations

Sponsors Gilead Sciences
Affiliations Gilead Sciences

Trial Dates

Initiation Dates
Planned : 01 Nov 2015

Actual : 11 Nov 2015
Primary Completion Dates
Planned : 01 Apr 2017

Actual : 09 May 2017
End Dates
Planned : 01 Jun 2020

Actual : 23 Oct 2019

Substudies/Extensions

An intensive pharmacokinetic (PK) substudy will be performed at the Weeks 4 or 8 visits in a subset of subjects (target n=30) at study sites able to conduct this testing. A pharmacogenomic substudy - for subjects who agree to participate and provide their additional specific consent, three blood samples will be obtained for the extraction of DNA for genomic testing and for potential genotyping to identify polymorphisms of drug metabolism enzymes,including Uridine 5'-diphospho-glucuronosyltransferase (UGT1A1) and additional biomarker testing such as human leukocyte antigen (HLA).These samples will be collected at Day 1.

Other Details

Design double-blind; multicentre; open; parallel; prospective; randomised
Phase of Trial Phase III
Location Australia; Belgium; Canada; England; France; Germany; Italy; Japan; Puerto Rico; Spain; Sweden; United Kingdom; USA
Focus Registrational; Therapeutic Use

Related Drugs

Drug Name	Highest Phase	Originator
Abacavir/dolutegravir/lamivudine - ViiV Healthcare	Marketed	GlaxoSmithKline, Shionogi ViiV Healthcare LLC
Bictegravir/emtricitabine/tenofovir alafenamide - Gilead Sciences	Marketed	Gilead Sciences

Interventions

Drugs	Route	Formulation
Abacavir/dolutegravir/lamivudine	Oral	Tablet
Bictegravir/emtricitabine/tenofovir alafenamidePrimary Drug	Oral	Tablet

Blinded Phase: ABC/DTG/3TC

ABC/DTG/3TC + B/F/TAF placebo for at least 48 weeks Drug: ABC/DTG/3TC (600/50/300 mg FDC tablets administered orally once daily without regard to food) Other Name: Triumeq® Drug: B/F/TAF Placebo (Tablets administered orally once daily without regard to food)

Blinded Phase: B/F/TAF

B/F/TAF + ABC/DTG/3TC placebo for at least 48 weeks Drug: B/F/TAF (50/200/25 mg FDC tablets administered orally once daily without regard to food) Other Name: Bictegravir (previously referred to as GS-9883)/Emtricitabine/Tenofovir Alafenamide, Biktarvy® [BVY] Drug: ABC/DTG/3TC Placebo (Tablets administered orally once daily without regard to food)

Open-Label Phase

At the End of Blinded Treatment Visit, if safety and efficacy of B/F/TAF is demonstrated following review of unblinded data, participants in a country where B/F/TAF FDC is not available will be given the option to receive B/F/TAF FDC in an open-label extension phase for up to 96 weeks, or until the product becomes accessible to subjects through an access program, or until Gilead Sciences elects to discontinue the study in that country, whichever occurs first. Drug: B/F/TAF (50/200/25 mg FDC tablets administered orally once daily without regard to food) Other Name: Bictegravir (previously referred to as GS-9883)/Emtricitabine/Tenofovir Alafenamide, Biktarvy® [BVY]

Results

Therapeutic efficacy

Results from 1844, 1878, 4030 and 4449 trials achieved its primary endpoint of HIV-1 RNA<50 copies/mL at week 48 with a proportion of 92 percent (129/140), showing that Biktarvy in older adults maintained high rates of virologic suppression^[3].

In a long term, open-label follow-up of phase III GS-US-380-1844 and GS-US380-1878 trial for two year post 48 week primary endpoints in adults who switched to Biktarvy from abacavir, dolutegravir and lamivudine (600/50/300mg) (ABC/DTG/3TC) or a boosted protease inhibitor (PI)-based regimen, overall, 98% patients displayed higher virologic suppression (n=561/570) whereas 97% (155/159) population with preexisting drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) also showed virologic suppression. Moreover 95% (42/44) subjects who were with archieved M184V/I also exhibited virologic suppression. Moreover, in a phase III GS-US-380-4030 in patients who switched from DTG+F/TAF or DTG+F/TDF to DTG+F/TAF or Biktarvy for 48 weeks, 99% (557/562) of all patients with any post-baseline visit and 99% (220/222) of patients with resistance to any class of anti-retroviral therapy, including those with archived M184V/I (79/81; 98 percent) had undetectable viral load (HIV-1 RNA <50 copies/mL) with no emergent drug resistance^[3]^[4].

Updated results from phase III trial who switched to bictegravir/emtricitabine/tenofovir from Dolutegravir/Abacavir/Lamivudine demonstrated RNA < 50 c/mL maintained in 99-100% at all timepoints through maximum of 168 weeks. No participant develop resistance to the regimen^[5]. Earlier data showed that at the primary endpoint of Week 48, switching to bictegravir/emtricitabine/tenofovir alafenamide was non-inferior to continuing ABC/DTG/3TC with 1.1% in the bictegravir/emtricitabine/tenofovir alafenamide arm and 0.4% in the ABC/DTG/3TC arm having HIV-1 RNA ≥50 c/mL (difference: 0.7%; 95% CI: -1.0% to 2.8%, p = 0.62). At week 48, no treatment-emergent resistance was detected, and no participants with pre-existing NRTI resistance mutations had HIV RNA >50 c/mL.The proportion of patients with HIV-1 RNA <50 c/mL was 93.6% and 95% in the bictegravir/emtricitabine/tenofovir alafenamide arm and ABC/DTG/3TC arm, respectively, according to FDA snapshot algorithm. The trial is designed to evaluate the efficacy and safety of switching from a regimen containing abacavir, dolutegravir and lamivudine (600/50/300mg) (ABC/DTG/3TC) to bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg tablet od in 565 virologically suppressed adults with HIV^[6].

Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) 50mg/200mg/25mg met the primary endpoint of non-inferiority in all four phase III studies, with comparable proportions of patients having HIV-1 RNA < 50 copies/mL (Studies 1489 and 1490) and HIV-1 RNA ≥ 50 copies/mL (Studies 1844 and 1878). One patient randomised to the protease inhibitor arm in Study 1878 developed an abacavir resistance mutation (L74V). No patients randomised to the bictegravir or dolutegravir arms developed treatment-emergent resistance^[1].

Adverse events

Results from 1844, 1878, 4030 and 4449 trials showed that biktarvy was generally well-tolerated; 11 patients experienced a grade 1 or 2 study drug-related adverse event (AE), four of which discontinued the study. No patient experienced a grade 3 or 4 drug-related AE or virologic failure. Most common AEs were nasopharyngitis and arthralgia (7 percent each)^[3].

Updated results from phase III trial demonstrated adverse events in 7% of the patients in the bictegravir/emtricitabine/tenofovir alafenamide arm. Most of the adverse events were grade 1 with most common was headache adverse events dur to premature study drug discontinuation were occurred in 1% of patients. Only 1 patient reported headache in open label phase^[5]. Earlier data from the trial showed a lower incidence of study drug-related adverse events (AEs) versus the ABC/DTG/3TC arm (8%vs 16%, p = 0.006; all grades), which were primarily mild or moderate in severity. The difference between groups was primarily driven by numerically more drug-related gastrointestinal (flatulence, nausea, diarrhoea) and neuropsychiatric (abnormal dreams and insomnia) AEs in the ABC/DTG/3TC arm. Headache (3% in both arms) was the most common study drug-related AE observed. AEs in few patients led to premature trial discontinuation (2% vs 1%). No patients in either treatment arm developed treatment-emergent resistance through Week 48. No renal AEs leading to discontinuations or cases of proximal renal tubulopathy were reported in either treatment arms. Lipid profiles were unchanged after switching to bictegravir/emtricitabine/tenofovir alafenamide from ABC/DTG/3TC and bone mineral density changes from baseline were the same between arms, at Week 48. The trial is designed to evaluate the efficacy and safety of switching from a regimen containing abacavir, dolutegravir and lamivudine (600/50/300mg) (ABC/DTG/3TC) to bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg tablet od in virologically suppressed adults with HIV^[6].

In four phase III studies (Studies 1489, 1490, 1844 and 1878), bictegravir/emtricitabine/tenofovir alafenamide 50mg/200mg/25mg was well tolerated. Treatment-emergent virological resistance was not seen. No patients discontinued study medication due to renal events and no cases of proximal renal tubulopathy or Fanconi syndrome were observed. Diarrhoea, nausea and headache were the most common adverse reactions^[1].

Pharmacokinetics

Results from the phase III trial in patients who switched to Bictegravir/Emtracitabine/Tenofovir from Dolutegravir/Abacavir/Lamivudine demonstrated stable GFR and lipid levels with slight increase in LDL at 96 weeks^[5].

Pharmacodynamics

Preclinical studies: in guinea-pig brain membrane, R 84760 had a 5-17 higher affinity for the κ-opioid receptor than enadoline and U 50488H. In rabbit vas deferens assay, R 85760 demonstrated a 2.5-210 times more potent κ-agonist activity than enadoline and U 50488H. In the phenylquinolone writhing test in mice, subcutaneously administered R 84760 produced an antinociceptive effect with 5-360 times higher potency than those of enadoline and U 50488H, and 40-850 times higher than those of morphine, pentazocine and butorphanol. Orally administered R 84760 demonstrated 20-2080 times higher potency than the above reference drugs. It did not develop tolerance to antinociception in contrast to morphine.

Publications

Gilead Sciences. Gileads Investigational Fixed-Dose Combination of Bictegravir, Emtricitabine and Tenofovir Alafenamide for the Treatment of HIV-1 Meets Primary Endpoint in Four Phase 3 Studies. Media-Rel 2017;.
Media Release
Gilead Sciences. New Findings on Gileads Biktarvy(Rm) Presented at AIDS 2020: Virtual Include Positive Switch Data in Older Adults. Media-Rel 2020;.
Media Release
Gilead Sciences. Gilead Presents Data on Biktarvy(Rm) (Bictegravir, Emtricitabine and Tenofovir Alafenamide) in Virologically Suppressed Adults, Including Those With Pre-Existing NRTI Resistance. Media-Rel 2019;.
Media Release
Brar I, Ruane P, Ward D, Molina J-m, Mills A, Berhe M, et al. Long-term Follow-up After a Switch to Bictegravir, Emtracitabine, Tenofovir Alafenamide from Dolutegravir, Abacavir, Lamivudine. IDW-2020 2020; abstr. 1028.
Available from: URL: https://www.eventscribe.net/2020/IDWeek/ajaxcalls/PosterInfo.asp?efp=VFhWUUpXVFA2ODg4&PosterID=292340&rnd=0.8797188
Gilead Sciences. Gilead Presents Results from Phase 3 Study Evaluating Patients Who Switched to Biktarvy(R) (Bictegravir, Emtricitabine and Tenofovir Alafenamide) from Regimen Containing Abacavir, Dolutegravir and Lamivudine. Media-Rel 2018;.
Media Release
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. ICDTHI-2020 2020; abstr. P124.
Available from: URL: http://www.hivglasgow.org/
Ramgopal M, Maggiolo F, Ward D, Lebouche B, Rizzardini G, Molina J?, et al. Pooled analysis of 4 international trials of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in adults aged > 65 or older demonstrating safety and efficacy: Week 48 Results. AIDS-2020 2020; abstr. OAB0403.
Available from: URL: https://onlinelibrary.wiley.com/doi/10.1002/jia2.25547
Gilead Sciences. Four-Year Biktarvy(Rm) Data Presented at IAS 2021 Demonstrate High Efficacy and Durable Viral Suppression in Treatment-Nave Adults. Media-Rel 2021;.
Media Release
Wohl D, Clarke A, Maggiolo F, Garner W, Laouri M, Martin H, et al. Patient-reported outcomes among HIV-1-infected adults randomized to B/F/TAF versus DTG/ABC/3TC in two Phase 3 controlled clinical trials over 48 weeks. AIDS-2018 2018; abstr. TUPEB148.
Available from: URL: http://programme.aids2018.org/Abstract/Abstract/4311
Andreatta K, Martin R, Chang S, Willkom M, Wei L, Graham H, et al. Previously undocumented preexisting resistance and maintenance of virologic suppression in HIV-1 RNA-suppressed patients switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF). IAS-2019 2019; abstr. MOPEB243.
Available from: URL: http://programme.ias2019.org/Abstract/Abstract/721
Snedecor SJ, Schroeder M, Van de Velde N. Indirect Treatment Comparison of 48-Week Efficacy and Safety of Cabotegravir + Rilpivirine Long-Acting Every 2 Months to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Suppressed HIV-1 Infected Participants. IDW-2021 2021; abstr. 875.
Available from: URL: https://academic.oup.com/ofid/article/8/Supplement_1/S529/6450338
Andreatta K, Sax PE, Wohl DA, D?Antoni ML, Huang H, Hindman J, et al. Efficacy of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) Versus Dolutegravir (DTG)-Based 3-Drug Regimens in Adults With HIV Who Have Suboptimal Antiretroviral Adherence. IDW-2023 2023; abstr. 1561.
Available from: URL: https://academic.oup.com/ofid/article/10/Supplement_2/ofad500.1396/7446554
Molina J-M, Ward D, Brar I, Mills A, Stellbrink H-J, Lopez-Cortes L, et al. Switch to Bictegravir/F/Taf from Dtg and Abc/3Tc. CROI-2018 2018; abstr. 22.
Available from: URL: http://www.croiconference.org/sessions/switch-bictegravirftaf-dtg-and-abc3tc
Andreatta K, Chang S, Delaney M, Willkom M, Martin R, Collins S, et al. Long-term efficacy among participants switched to bictegravir/emtricitabinetTenofovir alafenamide (B/F/TAF) from dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) with preexisting resistance and viral blips. IAS-2021 2021; abstr. PEB172.
Available from: URL: https://www.ias2021.org/
Andreatta K, Acosta R, D'Antoni ML, Porter DP, Chang S, Martin R, et al. Sustained viral suppression among participants with pre-existing M184V/I who switched to bictegravir/emtricitabine/tenofovir alafenamide. EACS-2019 2019; abstr. PE13/21.
Available from: URL: http://www.professionalabstracts.com/eacs2019/iplanner/#/list
Andreatta K, Acosta R, D'Antoni ML, Liu H, Chang S, Martin R, et al. Prevalence and risk factors of preexisting TAMs in clinical trial participants and sustained viral suppression after switching to bictegravir/emtricitabine/tenofovir alafenamide. EACS-2021 2021; abstr. PE1/6.
Available from: URL: https://eacs-conference2021.com/
Andreatta K, Acosta R, D?Antoni M, Porter D, Chang S, Mar-tin R, et al. Sustained viral suppression after switch to bictegravir/ emtricitabine/tenofovir alafenamide among clinical trial par- ticipants with preexisting M184V/I. ICDTHI-2020 2020; abstr. P123.
Available from: URL: http://www.hivglasgow.org/
Andreatta K, Willkom M, Martin R, Chang S, Martin H, Graham H, et al. Resistance Analyses of Bictegravir/Emtricitabine/Tenofovir Alafenamide Switch Studies. CROI-2018 2018; abstr. 506.
Available from: URL: http://www.croiconference.org/sessions/resistance-analyses-bictegraviremtricitabinetenofovir-alafenamide-switch-studies
Andreatta K, Willkom M, Martin R, Chang S, Liu H, Liu Y-P, et al. Long-Term B/F/Taf Switch Efficacy in Patients with Archived Preexisting Resistance. CROI-2019 2019; abstr. 552.
Available from: URL: http://www.croiconference.org/sessions/long-term-bftaf-switch-efficacy-patients-archived-preexisting-resistance
Rockstroh JK, Sax PE, Daar E, Walmsley S, Workowski K, Orkin C, et al. High Hbv and Hiv Suppression with Treatment of Hiv/Hbv Coinfection in B/F/Taf Studies. CROI-2018 2018; abstr. 618.
Available from: URL: http://www.croiconference.org/sessions/high-hbv-and-hiv-suppression-treatment-hivhbv-coinfection-bftaf-studies
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-naIve or switch studies. AIDS-2018 2018; abstr. THPEB077.
Available from: URL: http://programme.aids2018.org/Abstract/Abstract/11607
D'Antoni ML, Andreatta K, Acosta R, Martin H, Chang S, Martin R, et al. Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) Efficacy in Participants with Pre-existing Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. J-Acquir-Immune-Defic-Syndr 2021;.
PubMed | CrossRef Fulltext
Wohl D, Clarke A, Maggiolo F, Garner W, Laouri M, Martin H, et al. 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, and Tenofovir Alafenamide versus Co-formulated Abacavir, Dolutegravir, and Lamivudine. Patient-Patient-Centered-Outcome-Res 2018;.
PubMed | CrossRef Fulltext
Andreatta K, Willkom M, Martin R, Chang S, Wei L, Liu H, et al. Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. J-Antimicrob-Chemother 2019;.
PubMed | CrossRef Fulltext

Authors

Author	Total Publications	First Author	Last Author
Acosta R	6	2	-
Andreatta K	14	9	-
Arribas JR	1	-	-
Avihingsanon A	1	-	-
Benson P	1	-	-
Berhe M	1	-	-
Brar I	2	1	-
Brinson C	3	-	-
Callebaut C	1	-	-
Chang S	9	-	-
Cheng A	2	-	-
Clarke A	2	-	-
Collins S	6	-	-
Custodio JM	1	-	-
D'Antoni ML	3	1	-
D?Antoni M	2	-	-
D?Antoni ML	1	-	-
Daar E	1	-	-
DeJesus E	2	-	-
Delaney M	1	-	-
Gallant J	3	-	-
Garner W	3	-	-
Gilead Sciences	5	5	5
Graham H	7	-	-
Henry K	1	-	-
Hindman J	1	-	-
Huang H	2	-	-
Kityo C	1	-	-
Laouri M	2	-	-
Lebouche B	1	-	-
Liu H	4	-	-
Liu Y-P	1	-	-
Liu YP	1	-	-
Lopez-Cortes L	1	-	-
Maggiolo F	4	-	-
Makadzange T	1	-	-
Mar-tin R	1	-	-
Martin H	18	-	3
Martin R	8	-	-
McNicholl I	3	-	-
Mills A	2	-	-
Molina J-m	3	1	-
Molina J?	1	-	-
Orkin C	2	-	-
Pikora C	2	-	-
Piontkowsky D	1	-	-
Podzamczer D	1	-	-
Porter D	1	-	-
Porter DP	1	-	-
Quirk E	7	-	5
Ramgopal M	1	1	-
Rampogal M	1	-	-
Rizzardini G	1	-	-
Rockstroh J	1	-	-
Rockstroh JK	1	1	-
Romanova S	1	-	-
Ruane P	2	-	-
Sax PE	2	-	-
Schroeder M	1	-	-
SenGupta D	1	-	-
Snedecor SJ	1	1	-
Stellbrink H-J	1	-	-
Van de Velde N	1	-	1
Walmsley S	1	-	-
Wang H	1	-	-
Ward D	3	-	-
Wei L	2	-	-
Wei X	2	-	-
White K	3	-	2
White KL	8	-	8
Willkom M	8	-	-
Wohl D	3	2	-
Wohl DA	1	-	-
Workowski K	1	-	-
Yazdanpanah Y	1	-	-

Trial Centres

Investigators

Download Data (CSV)

Investigator	Centre Name	Trial Centre Country
Clinical Trials Mailbox Flowers Building, Granta Park Abington, Cambridge Postcode: CB21 6GT United Kingdom Fax: +441223897284 clinical.trials@gilead.com show details	Gilead Sciences International Ltd.	United-Kingdom
Gilead Study Director	Gilead Sciences	-
Szwarcberg J, MD	Gilead Sciences	-

Centres

Download Data (CSV)

Centre Name	Location	Trial Centre Country
-	Augusta, Georgia	USA
-	Austin, Texas	USA
-	Badalona	Spain
-	Barcelona	Spain
-	Berkley, Michigan	USA
-	Berlin	Germany
-	Beverly Hills, California	USA
-	Bonn	Germany
-	Boston, Massachusetts	USA
-	Brighton	United-Kingdom
-	Bronx, New York	USA
-	Buffalo, New York	USA
-	Charlotte, North Carolina	USA
-	Chicago, Illinois	USA
-	Cincinnati, Ohio	USA
-	Columbia, South Carolina	USA
-	Cordoba	Spain
-	Dallas, Texas	USA
-	Decatur, Georgia	USA
-	DeLand, Florida	USA
-	Detroit, Michigan	USA
-	Essen	Germany
-	Fort Lauderdale, Florida	USA
-	Fort Pierce, Florida	USA
-	Frankfurt am Main	Germany
-	Ghent	Belgium
-	Greenville, North Carolina	USA
-	Hamburg	Germany
-	Honolulu, Hawaii	USA
-	Houston, Texas	USA
-	Huntersville, North Carolina	USA
-	Kansas City, Missouri	USA
-	Longview, Texas	USA
-	Los Angeles, California	USA
-	Louisville, Kentucky	USA
-	München	Germany
-	Macon, Georgia	USA
-	Madrid	Spain
-	Manchester	United-Kingdom
-	Miami, Florida	USA
-	Miami Beach, Florida	USA
-	Minneapolis, Minnesota	USA
-	Montreal, Quebec	Canada
-	Munich	Germany
-	Nantes	France
-	New Orleans, Louisiana	USA
-	New York, New York	USA
-	Newark, New Jersey	USA
-	NICE Cedex 03	France
-	Oakland, California	USA
-	Orlando, Florida	USA
-	Palm Springs, California	USA
-	Paris	France
-	Paris cedex 20	France
-	Pensacola, Florida	USA
-	Philadelphia, Pennsylvania	USA
-	Phoenix, Arizona	USA
-	Roma	Italy
-	Sacramento, California	USA
-	Saint Louis, Missouri	USA
-	San Juan	Puerto-Rico
-	San Leandro, California	USA
-	Santa Fe, New Mexico	USA
-	Santiago de Compostela	Spain
-	Savannah, Georgia	USA
-	Seattle, Washington	USA
-	Sevilla	Spain
-	Spokane, Washington	USA
-	Springfield, Massachusetts	USA
-	Sydney, New South Wales	Australia
-	Tampa, Florida	USA
-	Vancouver, British Columbia	Canada
-	Vero Beach, Florida	USA
-	Washington, District of Columbia	USA
-	West Palm Beach, Florida	USA
-	Wilton Manors, Florida	USA
-	Winnipeg, Manitoba	Canada
Gilead Sciences Gilead Study Team GS-US-380-1844@gilead.com show details	-	-
Gilead Sciences International Ltd.	Abington	United-Kingdom

Trial History

Event Date	Event Type	Comment
15 Oct 2023	Results	Results of pooled analysis from /F/TAF Studies 1489, 1490, 4458, 1844 and 4030 presented at the IDWeek 2023 Updated 05 Feb 2024
10 Dec 2021	Results	Results of pooled analysis (n=1906) assessing virologic outcomes through 48 weeks of B/F/TAF treatment in individuals with pre-existing primary INSTI-R from 7 bictegravir/emtricitabine/tenofovir alafenamide studies (GS-US-380-1489/NCT02607930 and GS-US-380-1490/NCT02607956), (GS-US-380-1844/NCT02603120; GS-US-380-1878/NCT02603107; GS-US-380-4580/NCT03631732; GS-US-380-4030/NCT03110380 and GS-US-380-4449/NCT03405935), published in the JAIDS. Updated 22 Dec 2021
30 Oct 2021	Results	Results (n=2079) of pooled analysis assessing the safety and efficacy of switching adults with suppressed HIV to bictegravir/emtricitabine/tenofo - vir alafenamide (B/F/TAF) from 5 studies (Studies 1844, 1878, 4030, 4449, and 4580) presented at the 18th European AIDS Conference Updated 29 Dec 2021
03 Oct 2021	Results	Results comparing efficacy and safety of CAB LA + RPV LA Q2M to BIC/FTC/TAF using indirect treatment comparison using data from ATLAS [NCT02951052] and FLAIR [NCT02938520] ATLAS-2M [NCT03299049] NCT02603120 and NCT03110380 studies, presented at the IDWeek 2021. Updated 05 Feb 2022
21 Jul 2021	Results	Results assessimg long-term efficacy in patients who switched to bictegravir/emtricitabinetTenofovir alafenamide from DTG/ABC/3TC with preexisting resistance and viral blips, presented at the 11th International AIDS Society Conference on HIV Science Updated 06 Sep 2021
17 Jul 2021	Results	Results published in the Gilead Sciences Media Release. Updated 20 Jul 2021
17 Jul 2021	Results	According to a Gilead Sciences media release, data from the study were presented at the 11th International AIDS Society (IAS) Conference on HIV Science. Updated 20 Jul 2021
13 Nov 2020	Other trial event	Last checked against ClinicalTrials.gov record. ClinicalTrials.gov: US National Institutes of Health Updated 13 Nov 2020
12 Nov 2020	Biomarker Update	Biomarkers information updated Updated 06 Nov 2021
25 Oct 2020	Results	Results reporting outcomes of open-label extension part of this trial assessing long-term safety and efficacy presented at the IDWeek 2020 Updated 16 Dec 2020
08 Oct 2020	Results	Results of pooled analysis from following clinical studies: GS-US380-1844, GS-US380-1878, GS-US380-4030, GS-US380-4580, GS-US380-1474 and GS-US380-4449 presented at the 15th International Congress on Drug Therapy and HIV Infection Updated 11 Nov 2020
08 Oct 2020	Results	Results of an analysis of bictegravir/emtricitabine/tenofovir alafenamide assessing efficacy against HIV-1 subtype F from five clinical studies: GS-US-380-1489, GS-US-380-1490, GS-US-380-1844, GS-US-380-1878 and GS-US-380-4449 presented at the 15th International Congress on Drug Therapy and HIV Infection Updated 11 Nov 2020
10 Jul 2020	Results	Results (n=140) of pooled analysis from four clinical studies: GS-US380-1844, GS-US1878, GS-US4030 and GS-US4449 assessing safety and efficacy through week 48 presented at the 23rd International AIDS Conference Updated 31 Jul 2020
04 Jul 2020	Results	According to a Gilead Sciences media release, pooled analysis results from this and other three trials (1878, 4030 and 4449) were presented at the 23rd International AIDS Conference (AIDS 2020: Virtual). Updated 08 Jul 2020
04 Jul 2020	Results	Pooled analysis results from this and other three trials (1878, 4030 and 4449) presented in a Gilead Sciences media release. Updated 08 Jul 2020
01 Jul 2020	Other trial event	According to a Gilead Sciences media release, pooled analysis results from this and other three trials (1878, 4030 and 4449) will be presented at the 23rd International AIDS Conference (AIDS 2020: Virtual). Updated 08 Jul 2020
20 Dec 2019	Other trial event	Last checked against European Clinical Trials Database record. European Clinical Trials Database Updated 20 Dec 2019
09 Nov 2019	Results	Results of pooled analysis investigating the prevalence of pre-existing M184V/I and impact on virologic outcomes presented at the 17th European AIDS Conference Updated 27 Jan 2020
01 Nov 2019	Status change - completed	Status changed from active, no longer recruiting to completed. ClinicalTrials.gov: US National Institutes of Health Updated 19 Nov 2019
01 Nov 2019	Other trial event	This trial has been completed in Spain, according to European Clinical Trials Database record. European Clinical Trials Database Updated 05 Nov 2019
20 Aug 2019	Results	Results of a detailed analyses of pre-existing resistance in the two BIC/FTC/TAF switch studies and efficacy at week 48, published in the Journal of Antimicrobial Chemotherapy Updated 23 Aug 2019
09 Aug 2019	Other trial event	According to a Gilead Sciences media release, Biktarvy (bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg, BIC/FTC/TAF), has been approved in China for the treatment of HIV-1 infection, based on the results of 4 trials (1489, 1490, 1844 and 1878). Updated 13 Aug 2019
24 Jul 2019	Results	Results (n=510) who switched to Bictegravir/Emtricitabine/Tenofovir Alafenamide had high rates of virologic suppression in two open label extension studies (1844 and 1878), presented at the 10th International AIDS Society Conference on HIV Science. Updated 03 Oct 2019
26 Mar 2019	Other trial event	According to a Gilead Sciences media release, the Japan's Ministry of Health, Labour and Welfare (MHLW) has approved Biktarvy (bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg, BIC/FTC/TAF), a once-daily single tablet regimen (STR) for the treatment of HIV-1 infection. The approval of Biktarvy is supported by data from four Phase 3 studies (Studies 1489, 1490, 1844 and 1878). Updated 01 Apr 2019
07 Mar 2019	Results	Resistance analyses and virologic outcomes data from studies 1878 and 1844 were presented at the 26th Conference on Retroviruses and Opportunistic Infections. Updated 03 May 2019
06 Mar 2019	Results	According to a Gilead Sciences media release, results of retrospective analysis assessing the long-term Biktarvy switch efficacy in patients with archived pre-existing resistance from two phase 3 Biktarvy switch studies (Studies 1844 and 1878), were presented at the 2019 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. Updated 13 Mar 2019
06 Mar 2019	Results	Results of retrospective analysis assessing the long-term Biktarvy switch efficacy in patients with archived pre-existing resistance from two phase 3 Biktarvy switch studies (Studies 1844 and 1878) presented in a Gilead Sciences media release. Updated 13 Mar 2019
30 Jan 2019	Other trial event	This trial has been completed in Germany. European Clinical Trials Database Updated 04 Feb 2019
21 Nov 2018	Completion date	Planned End Date changed from 1 Jul 2019 to 1 Jun 2020. ClinicalTrials.gov: US National Institutes of Health Updated 19 Dec 2018
03 Oct 2018	Other trial event	According to Gilead Sciences media release,Based on the data from four phase III trials (Studies 1489, 1490, 1844 and 1878),that the Hong Kong Department of Health has approved Biktarvy,a once-daily single tablet regimen (STR) for the treatment of HIV-1 infection in adults. Hong Kong is the first market in Asia to approve Biktarvy. Updated 09 Oct 2018
27 Jul 2018	Results	Results from NCT02603120 and NCT02607930 presented at the 22nd International AIDS Conference Updated 10 Sep 2018
27 Jul 2018	Results	Results of pooled data from five trials (GS-US-380-1489, GS-US-380-1490, GS-US-380-1844, GS-US-380-1878 and GS-US-380-1961 ) were presented at the 22nd International AIDS Conference. Updated 29 Aug 2018
29 Jun 2018	Results	Results from NCT02607930 and NCT02603120 trials published in The Patient - Patient-Centered Outcomes Research Updated 25 Jul 2018
25 Jun 2018	Other trial event	According to a Gilead Sciences media release, the European Commission has granted Marketing Authorization for Biktarvy (bictegravir 50mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg), a once-daily single tablet regimen (STR) for the treatment of HIV-1 infection. The approval is based on four phase III trials (Studies 1489, 1490, 1844 and 1878). Updated 04 Jul 2018
27 Apr 2018	Other trial event	The Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion on the companys Marketing Authorization Application (MAA) for Biktarvy for the treatment of HIV-1 infection in adults without present or past evidence of viral resistance to the integrase class, emtricitabine or tenofovir. A European Commission decision is expected in mid-2018. Updated 03 May 2018
07 Mar 2018	Results	Results from studies 1489, 1490, 1878 and 1844 presented at the 25th Conference on Retroviruses and Opportunistic Infections Updated 20 Apr 2018
07 Mar 2018	Results	Results assessing safety and efficacy presented at the 25th Conference on Retroviruses and Opportunistic Infections Updated 18 Apr 2018
07 Mar 2018	Results	Results (n=572), of an integrated resistance analysis from 2 phase 3 clinical trials (Study 1878 and study 1844) presented at the 25th Conference on Retroviruses and Opportunistic Infections Updated 18 Apr 2018
05 Mar 2018	Other trial event	According to a Gilead Sciences media release, Jean-Michel Molina is lead study investigator. Updated 08 Mar 2018
05 Mar 2018	Results	According to a Gilead Sciences media release, data from this trial were presented at the 2018 Conference on Retroviruses and Opportunistic Infections (CROI). Updated 08 Mar 2018
05 Mar 2018	Results	48-week results published in the Gilead Sciences Media Release Updated 08 Mar 2018
08 Feb 2018	Other trial event	According to a Gilead Sciences media release, Gilead plans to present data from this studies at scientific conferences in 2018. Updated 09 Feb 2018
08 Feb 2018	Other trial event	According to a Gilead Sciences media release, based on the data from four phase III trials (Studies 1489, 1490, 1844 and 1878), the U.S. Food and Drug Administration (FDA) has approved Biktarvy, an investigational, once-daily single tablet regimen containing bictegravir (50 mg) (BIC), a novel investigational integrase strand transfer inhibitor, and emtricitabine/tenofovir alafenamide (200/25 mg) (FTC/TAF) for the treatment of HIV-1 infection in adults. Updated 09 Feb 2018
17 Nov 2017	Completion date	Planned End Date changed from 1 Jun 2019 to 1 Jul 2019. ClinicalTrials.gov: US National Institutes of Health Updated 23 Nov 2017
10 Aug 2017	Other trial event	According to a Gilead Sciences media release, the US FDA has granted priority review for the company's NDA for BIC/FTC/TAF, and the FDA has set a target action date under the Prescription Drug User Fee Act (PDUFA) of February 12, 2018. Updated 16 Aug 2017
13 Jul 2017	Other trial event	The company's MAA for BIC/FTC/TAF has been fully validated and is now under evaluation by the European Medicines Agency (EMA), according to a Gilead Sciences media release. The MAA was supported by data from this and 3 other phase III trials. Updated 17 Jul 2017
12 Jun 2017	Other trial event	According to a Gilead Sciences media release, the company plans to submit a marketing authorization application for BIC/FTC/TAF in the European Union in the third quarter of 2017. Updated 16 Jun 2017
12 Jun 2017	Other trial event	According to a Gilead Sciences media release, based on the data from four phase III trials (Studies 1489, 1490, 1844 and 1878), the company has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for an investigational, once-daily single tablet regimen containing bictegravir (50 mg) (BIC), a novel investigational integrase strand transfer inhibitor, and emtricitabine/tenofovir alafenamide (200/25 mg) (FTC/TAF) for the treatment of HIV-1 infection in adults. Updated 16 Jun 2017
30 May 2017	Other trial event	Gilead plans to submit data from this trial for presentations at scientific conferences in 2017, as reported in a media release. Updated 02 Jun 2017
30 May 2017	Results	Results published in the Gilead Sciences Media Release Updated 02 Jun 2017
30 May 2017	Other trial event	According to a Gilead Sciences media release, based on the data from this and other three Phase III trials (Studies 1489, 1490, 1844 and 1878) company is planning U.S. NDA Submission in Q2 2017 and EU MAA Filing in Q3 2017. Updated 02 Jun 2017
30 May 2017	Endpoint met	Primary endpoint has been met. (Proportion of participants with virologic failure (HIV-1 RNA 50 copies/mL) as defined by the modified US FDA snapshot algorithm, as reported in a Gilead Sciences media release. Updated 02 Jun 2017
19 May 2017	Completion date	Planned End Date changed from 1 Apr 2019 to 1 Jun 2019. ClinicalTrials.gov: US National Institutes of Health Updated 26 May 2017
27 Jul 2016	Status change - active, no longer recruiting	Status changed from recruiting to active, no longer recruiting. ClinicalTrials.gov: US National Institutes of Health Updated 02 Aug 2016
02 Mar 2016	Other trial event	New source identified and integrated (EU Clinical Trials Register;EudraCT2015-004025-14). European Clinical Trials Database Updated 09 Mar 2016
01 Dec 2015	Status change - recruiting	Status changed from not yet recruiting to recruiting, as reported by ClinicalTrials.gov. ClinicalTrials.gov: US National Institutes of Health Updated 05 Dec 2015
17 Nov 2015	New trial record	New trial record ClinicalTrials.gov: US National Institutes of Health Updated 17 Nov 2015

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