Clinical trial NCT02362503: Attachment Inhibitor Comparison in Heavily Treatment Experienced Patients
Official title: A Multi-arm, Phase 3, Randomized, Placebo Controlled, Double Blind Clinical Trial to Investigate the Efficacy and Safety of Fostemsavir (BMS-663068/GSK3684934) in Heavily Treatment Experienced Subjects Infected With Multi-drug Resistant HIV-1 (BRIGHTE Study)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: HIV Infections
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2015-02-13
Enrollment: 371
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether the BMS Attachment Inhibitor (BMS-663068) is effective in the treatment of heavily treatment experienced HIV-1 patients with multi-drug resistance.


Eligibility criteria: Inclusion Criteria:

* Men and non-pregnant women with chronic HIV-1 infection
* Antiretroviral-experienced with documented historical or baseline resistance, intolerability, and/or contraindications to antiretrovirals in at least three classes
* Failing current antiretroviral regimen with a confirmed plasma HIV-1 RNA ≥ 400 c/mL (first value from Investigator, second from Screening labs)
* Must have ≤ 2 classes with at least 1 but no more than 2 fully-active antiretrovirals remaining which can be effectively combined to form a viable new regimen, based on current and/or documented historical resistance testing and tolerability and safety
* Able to receive ≥ 1 fully active approved antiretroviral as part of the OBT from Day 9 onwards in the Randomized Cohort
* Subjects without any remaining fully active approved antiretroviral may be enrolled in the Non-Randomized Cohort

Exclusion Criteria:

* Chronic untreated Hepatitis B virus (HBV) (however, patients with chronic treated HBV are eligible)
* HIV-2 infection
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 7 x ULN
* Alkaline Phosphatase \> 5 x ULN
* Bilirubin ≥ 1.5 x Upper limit of normal (ULN) (unless subject is currently on atazanavir and has predominantly unconjugated hyperbilirubinemia)

Primary outcomes:
measure: Mean Change in Logarithm to the Base 10 (log10) HIV-1 Ribonucleic Acid (RNA) From Day 1 at Day 8-Randomized Cohort
timeFrame: Day 1 and Day 8
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA Decreases From Day 1 That Exceed 0.5 log10 c/mL and 1.0 log10 c/mL at Day 8-Randomized Cohort
timeFrame: Day 1 and Day 8
measure: Percentage of Participants With HIV-1 RNA <40 c/mL at Weeks 24, 48 and 96-Randomized Cohort
timeFrame: At Weeks 24, 48 and 96
measure: Number of Participants With On-treatment Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation (AELD)-Randomized Cohort
timeFrame: Up to Week 96 analysis cut-off date
measure: Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort
timeFrame: Baseline and up to Week 96 analysis cut-off date
measure: Number of Participants With Toxicity Grade Increase in Hematology Results to Grade 3-4 Relative to Baseline-Randomized Cohort
timeFrame: Baseline and up to Week 96 analysis cut-off date
measure: Number of Participants With Centers for Disease Control (CDC) Class C Events-Randomized Cohort
timeFrame: Up to Week 96 analysis cut-off date
measure: Change From Day 1 in Cluster of Differentiation (CD) 4+ T-cell Count at Day 8-Randomized Cohort
timeFrame: Day 1 and Day 8
measure: Change in CD4+ T- Cell Count Percentage From Day 1 at Day 8-Randomized Cohort
timeFrame: Day 1 and Day 8
measure: Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 96-Randomized Cohort
timeFrame: Baseline and at Day 8, Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84 and 96
measure: Change From Baseline in CD4+ T- Cell Count Through Week 96-Randomized Cohort
timeFrame: Baseline and at Day 8, Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84 and 96
measure: Change From Baseline in CD4+ T- Cell Count Percentage Through Week 96
timeFrame: Baseline and at Day 8, Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84 and 96
measure: Number of Participants With Treatment-emergent Viral Genotypic Substitution of Interest in the GP160 Domain as a Measure of Genotypic Resistance-Randomized Cohort
timeFrame: Week 96
measure: Number of Participants With Indicated Fold Change Ratio (FCR) Using the Monogram PhenoSense Entry Assay-Randomized Cohort
timeFrame: Week 96
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Palm Springs
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: New Haven
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Fort Pierce
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: West Palm Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Wilton Manors
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Savannah
country: United States
facility: GSK Investigational Site
state: Georgia
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Southfield
country: United States
facility: GSK Investigational Site
state: Michigan
city: Hillsborough
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Newark
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Bronx
country: United States
facility: GSK Investigational Site
state: New York
city: Manhasset
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Durham
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Tulsa
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Bellaire
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma De Bueno
country: Argentina
facility: GSK Investigational Site
city: Cordoba
country: Argentina
facility: GSK Investigational Site
city: Cordoba
country: Argentina
facility: GSK Investigational Site
city: Rosario
country: Argentina
facility: GSK Investigational Site
city: Darlinghurst
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Melbourne
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Antwerpen
country: Belgium
facility: GSK Investigational Site
city: Brussels
country: Belgium
facility: GSK Investigational Site
city: Belo Horizonte
country: Brazil
facility: GSK Investigational Site
city: Campinas
country: Brazil
facility: GSK Investigational Site
city: Curitiba
country: Brazil
facility: GSK Investigational Site
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
city: RibeirAo PretoSP
country: Brazil
facility: GSK Investigational Site
city: Rio de Janeiro
country: Brazil
facility: GSK Investigational Site
city: Salvador
country: Brazil
facility: GSK Investigational Site
city: Sao Paulo
country: Brazil
facility: GSK Investigational Site
city: Sao Paulo
country: Brazil
facility: GSK Investigational Site
city: Sao Paulo
country: Brazil
facility: GSK Investigational Site
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sainte-Foy
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Santiago de Chile
country: Chile
facility: GSK Investigational Site
city: Santiago
country: Chile
facility: GSK Investigational Site
city: Santiago
country: Chile
facility: GSK Investigational Site
city: Santiago
country: Chile
facility: GSK Investigational Site
city: Temuco
country: Chile
facility: GSK Investigational Site
city: Bogota
country: Colombia
facility: GSK Investigational Site
city: Bogota
country: Colombia
facility: GSK Investigational Site
city: Cali
country: Colombia
facility: GSK Investigational Site
city: Bordeaux
country: France
facility: GSK Investigational Site
city: Marseille
country: France
facility: GSK Investigational Site
city: Nantes cedex 1
country: France
facility: GSK Investigational Site
city: Paris cedex 14
country: France
facility: GSK Investigational Site
city: Paris cedex 20
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Dortmund
country: Germany
facility: GSK Investigational Site
city: Frankfurt
country: Germany
facility: GSK Investigational Site
city: Freiburg
country: Germany
facility: GSK Investigational Site
city: MUnchen
country: Germany
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Dublin
country: Ireland
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Modena
country: Italy
facility: GSK Investigational Site
city: Monza MB
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Torino
country: Italy
facility: GSK Investigational Site
city: Chihuahua
country: Mexico
facility: GSK Investigational Site
city: Distrito Federal
country: Mexico
facility: GSK Investigational Site
city: Distrito Federal
country: Mexico
facility: GSK Investigational Site
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
city: Mexico City
country: Mexico
facility: GSK Investigational Site
city: Mexico
country: Mexico
facility: GSK Investigational Site
city: Utrecht
country: Netherlands
facility: GSK Investigational Site
city: Iquitos
country: Peru
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Szczecin
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Lisboa
country: Portugal
facility: GSK Investigational Site
city: Lisboa
country: Portugal
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Constanta
country: Romania
facility: GSK Investigational Site
city: Irkutsk
country: Russian Federation
facility: GSK Investigational Site
city: Krasnodar
country: Russian Federation
facility: GSK Investigational Site
city: Auckland Park Johannesb
country: South Africa
facility: GSK Investigational Site
city: Benoni
country: South Africa
facility: GSK Investigational Site
city: Bloemfontein
country: South Africa
facility: GSK Investigational Site
city: Cape Town
country: South Africa
facility: GSK Investigational Site
city: Dundee
country: South Africa
facility: GSK Investigational Site
city: Durban
country: South Africa
facility: GSK Investigational Site
city: Observatory Cape Town
country: South Africa
facility: GSK Investigational Site
city: Port Elizabeth
country: South Africa
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Bournemouth
country: United Kingdom
facility: GSK Investigational Site
city: Leicester
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Kozal M, Aberg J, Pialoux G, Cahn P, Thompson M, Molina JM, Grinsztejn B, Diaz R, Castagna A, Kumar P, Latiff G, DeJesus E, Gummel M, Gartland M, Pierce A, Ackerman P, Llamoso C, Lataillade M; BRIGHTE Trial Team. Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection. N Engl J Med. 2020 Mar 26;382(13):1232-1243. doi: 10.1056/NEJMoa1902493.
citation: Gartland M, Cahn P, DeJesus E, Diaz RS, Grossberg R, Kozal M, Kumar P, Molina JM, Mendo Urbina F, Wang M, Du F, Chabria S, Clark A, Garside L, Krystal M, Mannino F, Pierce A, Ackerman P, Lataillade M. Week 96 Genotypic and Phenotypic Results of the Fostemsavir Phase 3 BRIGHTE Study in Heavily Treatment-Experienced Adults Living with Multidrug-Resistant HIV-1. Antimicrob Agents Chemother. 2022 Jun 21;66(6):e0175121. doi: 10.1128/aac.01751-21. Epub 2022 May 3.
citation: Anderson SJ, Murray M, Cella D, Grossberg R, Hagins D, Towner W, Wang M, Clark A, Pierce A, Llamoso C, Ackerman P, Lataillade M. Patient-Reported Outcomes in the Phase III BRIGHTE Trial of the HIV-1 Attachment Inhibitor Prodrug Fostemsavir in Heavily Treatment-Experienced Individuals. Patient. 2022 Jan;15(1):131-143. doi: 10.1007/s40271-021-00534-y. Epub 2021 Jun 28.
citation: Lataillade M, Lalezari JP, Kozal M, Aberg JA, Pialoux G, Cahn P, Thompson M, Molina JM, Moreno S, Grinsztejn B, Diaz RS, Castagna A, Kumar PN, Latiff GH, De Jesus E, Wang M, Chabria S, Gartland M, Pierce A, Ackerman P, Llamoso C. Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced individuals: week 96 results of the phase 3 BRIGHTE study. Lancet HIV. 2020 Nov;7(11):e740-e751. doi: 10.1016/S2352-3018(20)30240-X.
citation: Lagishetty C, Moore K, Ackerman P, Llamoso C, Magee M. Effects of Temsavir, Active Moiety of Antiretroviral Agent Fostemsavir, on QT Interval: Results From a Phase I Study and an Exposure-Response Analysis. Clin Transl Sci. 2020 Jul;13(4):769-776. doi: 10.1111/cts.12763. Epub 2020 Mar 19.