Attachment Inhibitor Comparison in Heavily Treatment Experienced Patients

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Other: Placebo; Drug: BMS-663068

• Study Type: Interventional
• Enrollment (Actual): 371
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1141ACG
    • GSK Investigational Site
  • Buenos Aires, Argentina, C1155ADP
    • GSK Investigational Site
  • Buenos Aires, Argentina, C1202ABB
    • GSK Investigational Site
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1426ABP
      • GSK Investigational Site
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1405CKC
      • GSK Investigational Site
  • Córdova
    • Cordoba, Córdova, Argentina, 5000
      • GSK Investigational Site
    • Cordoba, Córdova, Argentina, X5000JJS
      • GSK Investigational Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000PBJ
      • GSK Investigational Site
• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • GSK Investigational Site
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • GSK Investigational Site
• Belgium
  • Antwerpen, Belgium, 2000
    • GSK Investigational Site
  • Brussels, Belgium, 1000
    • GSK Investigational Site
• Brazil
  • Belo Horizonte, Brazil, 30130-100
    • GSK Investigational Site
  • Ribeirao Preto, Brazil, 14048-900
    • GSK Investigational Site
  • Rio de Janeiro, Brazil, 21040-900
    • GSK Investigational Site
  • Salvador, Brazil, 40110-060
    • GSK Investigational Site
  • Paraná
    • Curitiba, Paraná, Brazil, 80240-280
      • GSK Investigational Site
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • GSK Investigational Site
  • São Paulo
    • Campinas, São Paulo, Brazil, 13015-080
      • GSK Investigational Site
    • Sao Paulo, São Paulo, Brazil, 01416-901
      • GSK Investigational Site
    • Sao Paulo, São Paulo, Brazil, 04040-002
      • GSK Investigational Site
    • Sao Paulo, São Paulo, Brazil, 04121-000
      • GSK Investigational Site
• Canada
  • Quebec, Canada, G1V 4G5
    • GSK Investigational Site
  • Vancouver, Canada, V6H3N1
    • GSK Investigational Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y8
      • GSK Investigational Site
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M5G 2N2
      • GSK Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H2L 4P9
      • GSK Investigational Site
    • Montreal, Quebec, Canada, H2L 5B1
      • GSK Investigational Site
• Chile
  • Santiago, Chile, 7500520
    • GSK Investigational Site
  • Temuco, Chile, 4781151
    • GSK Investigational Site
  • Región Metro De Santiago
    • Santiago, Región Metro De Santiago, Chile, 8330074
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile, 8900088
      • GSK Investigational Site
    • Santiago Centro, Región Metro De Santiago, Chile, 8360159
      • GSK Investigational Site
• Colombia
  • Bogota, Colombia, 111311
    • GSK Investigational Site
  • Bogotá, Colombia, 110111
    • GSK Investigational Site
  • Cali, Valle Del Cauca, Colombia, 760032
    • GSK Investigational Site
• France
  • Bordeaux cedex, France, 33076
    • GSK Investigational Site
  • Marseille, France, 13009
    • GSK Investigational Site
  • Nantes, France, 44093
    • GSK Investigational Site
  • Paris, France, 75018
    • GSK Investigational Site
  • Paris, France, 75013
    • GSK Investigational Site
  • Paris, France, 75004
    • GSK Investigational Site
  • Paris Cedex 12, France, 75571
    • GSK Investigational Site
  • Paris cedex 10, France, 75475
    • GSK Investigational Site
  • Paris cedex 20, France, 75970
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 13353
    • GSK Investigational Site
  • Berlin, Germany, 10439
    • GSK Investigational Site
  • Berlin, Germany, 12157
    • GSK Investigational Site
  • München, Germany, 80336
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Freiburg, Baden-Wuerttemberg, Germany, 79106
      • GSK Investigational Site
  • Hessen
    • Frankfurt, Hessen, Germany, 60590
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Dortmund, Nordrhein-Westfalen, Germany, 44137
      • GSK Investigational Site
• Greece
  • Athens, Greece, 16121
    • GSK Investigational Site
  • Thessaloniki, Greece, 54636
    • GSK Investigational Site
• Ireland
  • Dublin, Ireland, Dublin 7
    • GSK Investigational Site
• Italy
  • Modena, Italy, 41124
    • GSK Investigational Site
  • Monza, Italy, 20900
    • GSK Investigational Site
  • Lazio
    • Roma, Lazio, Italy, 00149
      • GSK Investigational Site
    • Roma, Lazio, Italy, 00168
      • GSK Investigational Site
  • Lombardia
    • Milano, Lombardia, Italy, 20127
      • GSK Investigational Site
    • Milano, Lombardia, Italy, 20157
      • GSK Investigational Site
  • Piemonte
    • Torino, Piemonte, Italy, 10149
      • GSK Investigational Site
• Mexico
  • Chihuahua, Mexico, 31000
    • GSK Investigational Site
  • Ciudad de Mexico, Mexico, 6700
    • GSK Investigational Site
  • Distrito Federal, Mexico, 06470
    • GSK Investigational Site
  • Mexico, Mexico, 14000
    • GSK Investigational Site
  • Estado De México
    • Ciudad de México, Estado De México, Mexico, ?03100
      • GSK Investigational Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • GSK Investigational Site
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • GSK Investigational Site
• Peru
  • Lima, Peru, 1
    • GSK Investigational Site
  • Lima, Peru, Lima 31
    • GSK Investigational Site
  • Lima, Peru, 11
    • GSK Investigational Site
  • Lima, Peru, 14
    • GSK Investigational Site
  • Loreto
    • Iquitos, Loreto, Peru, Iqui 01
      • GSK Investigational Site
• Poland
  • Szczecin, Poland, 70-376
    • GSK Investigational Site
  • Warszawa, Poland, 01-201
    • GSK Investigational Site
• Portugal
  • Lisboa, Portugal, 1069-166
    • GSK Investigational Site
  • Lisbon, Portugal, 1649-035
    • GSK Investigational Site
• Puerto Rico
  • San Juan, Puerto Rico, 909
    • GSK Investigational Site
• Romania
  • Bucharest, Romania, 021105
    • GSK Investigational Site
• Russian Federation
  • Irkutsk, Russian Federation, 664035
    • GSK Investigational Site
  • Krasnodar, Russian Federation, 350015
    • GSK Investigational Site
• South Africa
  • Cape Town, South Africa, 7505
    • GSK Investigational Site
  • Durban, South Africa, 7925
    • GSK Investigational Site
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6001
      • GSK Investigational Site
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • GSK Investigational Site
  • Gauteng
    • Benoni, Gauteng, South Africa, 1500
      • GSK Investigational Site
    • Johannesburg, Gauteng, South Africa, 2092
      • GSK Investigational Site
  • KwaZulu- Natal
    • Dundee, KwaZulu- Natal, South Africa, 3000
      • GSK Investigational Site
  • Western Province
    • Observatory, Western Province, South Africa, 7925
      • GSK Investigational Site
• Spain
  • Badalona, Barcelona, Spain, 8916
    • GSK Investigational Site
  • Barcelona, Spain, 08036
    • GSK Investigational Site
  • Madrid, Spain, 28034
    • GSK Investigational Site
  • Seville, Sevilla, Spain, 41014
    • GSK Investigational Site
• Taiwan
  • Taipei, Taiwan, 10002
    • GSK Investigational Site
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • GSK Investigational Site
  • Leicestershire, United Kingdom, LE1 5WW
    • GSK Investigational Site
  • London, United Kingdom, SW10 9NH
    • GSK Investigational Site
• United States
  • California
    • Los Angeles, California, United States, 90069
      • GSK Investigational Site
    • Los Angeles, California, United States, 90027
      • GSK Investigational Site
    • Los Angeles, California, United States, 90033
      • GSK Investigational Site
    • Los Angeles, California, United States, 90008
      • GSK Investigational Site
    • Palm Springs, California, United States, 92262
      • GSK Investigational Site
    • San Francisco, California, United States, 94115
      • GSK Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80262
      • GSK Investigational Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • GSK Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • GSK Investigational Site
    • Washington, District of Columbia, United States, 20009
      • GSK Investigational Site
  • Florida
    • Fort Pierce, Florida, United States, 34982
      • GSK Investigational Site
    • Oakland Park, Florida, United States, 33306
      • GSK Investigational Site
    • Orlando, Florida, United States, 32801
      • GSK Investigational Site
    • West Palm Beach, Florida, United States, 33407
      • GSK Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30312
      • GSK Investigational Site
    • Atlanta, Georgia, United States, 30308
      • GSK Investigational Site
    • Savannah, Georgia, United States, 31401
      • GSK Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • GSK Investigational Site
    • Chicago, Illinois, United States, 60613
      • GSK Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • GSK Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • GSK Investigational Site
    • Baltimore, Maryland, United States, 21287
      • GSK Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 211
      • GSK Investigational Site
  • Michigan
    • Southfield, Michigan, United States, 48075
      • GSK Investigational Site
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • GSK Investigational Site
    • Newark, New Jersey, United States, 07102
      • GSK Investigational Site
  • New York
    • Bronx, New York, United States, 10467
      • GSK Investigational Site
    • Manhasset, New York, United States, 11030
      • GSK Investigational Site
    • New York, New York, United States, 10029
      • GSK Investigational Site
    • New York, New York, United States, 10010
      • GSK Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • GSK Investigational Site
    • Durham, North Carolina, United States, 27710
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0405
      • GSK Investigational Site
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74135
      • GSK Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • GSK Investigational Site
  • Texas
    • Bellaire, Texas, United States, 77401
      • GSK Investigational Site
    • Dallas, Texas, United States, 75246
      • GSK Investigational Site
    • Dallas, Texas, United States, 75235
      • GSK Investigational Site
    • Houston, Texas, United States, 77098
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A1: BMS-663068; Phase 1: BMS-663068 600 mg tablets orally twice daily for 8 days. Phase 2: BMS-663068 600 mg tablets orally twice daily for 48 weeks or longer.	Drug: BMS-663068; BMS-663068
Active Comparator: B1: Placebo + BMS-663068; Phase 1: Placebo twice daily for 8 days. Phase 2: BMS-663068 600 mg tablets orally twice daily for 48 weeks or longer.	Other: Placebo; Placebo; Drug: BMS-663068; BMS-663068
Experimental: BMS-663068; BMS-663068 600 mg tablets orally twice daily for 48 weeks or longer.	Drug: BMS-663068; BMS-663068

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Logarithm to the Base 10 (log10) HIV-1 Ribonucleic Acid (RNA) From Day 1 at Day 8-Randomized Cohort	Plasma samples were collected for analysis of HIV-1 RNA. Mean change in log10 HIV-1 RNA from Day 1 was estimated using analysis of covariance (ANCOVA) with log10 HIV-1 RNA change from Day 1 at Day 8 as dependent variable, treatment (fostemsavir or placebo) as an independent variable, and Day 1 log10 HIV-1 RNA as a continuous covariate. Change from Day 1 was calculated as value at Day 8 minus value at Day 1. The analysis was performed on Intent-to-Treat Exposed (ITT-E) Population which comprised of all randomized participants who received at least one dose of study treatment. Missing HIV-1 RNA values at Day 8 were imputed using (a) Day 1 Observation Carried Forward (D1OCF) for participants without a value during blinded treatment (i.e, imputing a zero change from Day 1) or (b) Last Observation Carried Forward (LOCF) for participants with an early value during blinded treatment before the Day 8 analysis visit window.	Day 1 and Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	The percentage of participants in the Randomized Cohort with HIV-1 RNA decreases from Day 1 that exceed 0.5 log10 c/mL and 1.0 log10 c/mL at Day 8 was determined by comparing HIV-1 RNA Day 1 measurement of each participant to their Day 8 measurement. This was an ITT analysis that classified participants without HIV-1 RNA at Day 1 or Day 8 as failures. The percentage of responders along with 95% confidence interval based on Wilson score is presented.	Day 1 and Day 8
Percentage of Participants With HIV-1 RNA <40 c/mL at Weeks 24, 48 and 96-Randomized Cohort	The durability of response (that is, the number of participants achieving HIV-1 RNA <40 c/mL) at Weeks 24, 48 and 96 of open-label fostemsavir plus OBT in the Randomized Cohort was assessed using the Food and Drug Administration (FDA) snapshot algorithm in which participants without HIV-1 RNA at Weeks 24, 48 and 96 or those who changed OBT due to lack of efficacy through Weeks 24, 48 and 96 were counted as failures. The percentage of participants in the Randomized Cohort who achieved virologic success (HIV-1 RNA <40 c/mL) at Weeks 24, 48 and 96 is presented along with 95% Wilson confidence interval. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.	At Weeks 24, 48 and 96
Number of Participants With On-treatment Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation (AELD)-Randomized Cohort	An SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or causes prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; an important medical event that may jeopardize the participant or require intervention. Number of participants with on-treatment SAEs and AEs leading to withdrawal of study treatment is presented. SAEs and AELDs were collected in Safety Population which comprised of all participants who received at least one dose of study treatment. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.	Up to Week 96 analysis cut-off date
Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort	Laboratory toxicities were graded for severity according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) grading system: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (potentially life-threatening). Baseline is defined as the latest pre-dose assessment. The number of participants with clinical chemistry toxicity grade increase to Grade 3-4 at anytime post-Baseline relative to Baseline is presented. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.	Baseline and up to Week 96 analysis cut-off date
Number of Participants With Toxicity Grade Increase in Hematology Results to Grade 3-4 Relative to Baseline-Randomized Cohort	Laboratory toxicities were graded for severity according to the DAIDS grading system: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (potentially life-threatening). Baseline is defined as the latest pre-dose assessment. The number of participants with hematology toxicity grade increase to Grade 3-4 at anytime post-Baseline relative to Baseline is presented. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.	Baseline and up to Week 96 analysis cut-off date
Number of Participants With Centers for Disease Control (CDC) Class C Events-Randomized Cohort	Disease progression during open label fostemsavir plus OBT was assessed based on the occurrence of new AIDS defining events (CDC Class C events) or death. The number of participants with on-treatment CDC Class C AIDS events is presented. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.	Up to Week 96 analysis cut-off date
Change From Day 1 in Cluster of Differentiation (CD) 4+ T-cell Count at Day 8-Randomized Cohort	CD4+ T- cell counts were assessed by flow cytometry. Mean change in CD4+ T- cell count from Day 1 at Day 8 was analyzed using one-way ANCOVA with change of CD4+ cell counts from Day 1 at Day 8 as the dependent variable, treatment (fostemsavir or placebo) as an in-dependent variable, and Day 1 CD4+ cell count as a continuous covariate. Change from Day 1 was calculated as value at Day 8 minus value at Day 1. Missing CD4+ cell count values at Day 8 were imputed using (a) D1OCF for participants without a value during blinded treatment (i.e., imputing a zero change from Day 1), or (b) LOCF for participants with an early value during blinded treatment before the Day 8 analysis visit window.	Day 1 and Day 8
Change in CD4+ T- Cell Count Percentage From Day 1 at Day 8-Randomized Cohort	CD4+ T- cell counts were assessed by flow cytometry. Mean change in CD4+ T- cell count percentage from Day 1 at Day 8 was analyzed using one-way ANCOVA with change of CD4+ cell count percentage from Day 1 at Day 8 as the dependent variable, treatment (fostemsavir or placebo) as an independent variable, and Day 1 CD4+ cell count percentage as a continuous covariate. Change from Day 1 was calculated as value at Day 8 minus value at Day 1. Missing CD4+ cell count values at Day 8 were imputed using (a) D1OCF for participants without a value during blinded treatment (ie, imputing a zero change from Day 1), or (b) LOCF for participants with an early value during blinded treatment before the Day 8 analysis visit window.	Day 1 and Day 8
Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 96-Randomized Cohort	Blood samples were collected for the analysis of HIV-1 RNA. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment. Change from Baseline was calculated as the value at post-dose visit minus the value at Baseline. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.	Baseline and at Day 8, Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84 and 96
Change From Baseline in CD4+ T- Cell Count Through Week 96-Randomized Cohort	CD4+ T- cell counts were assessed by flow cytometry. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment. Change from Baseline was calculated as the value at post-dose visit minus the value at Baseline.	Baseline and at Day 8, Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84 and 96
Change From Baseline in CD4+ T- Cell Count Percentage Through Week 96	Percentage CD4+ T- cell counts were assessed by flow cytometry. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment. Change from Baseline was calculated as the value at post-dose visit minus the value at Baseline.	Baseline and at Day 8, Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84 and 96
Number of Participants With Treatment-emergent Viral Genotypic Substitution of Interest in the GP160 Domain as a Measure of Genotypic Resistance-Randomized Cohort	Plasma samples were collected for emergent drug resistance testing. The number of participants with emergent viral genotypic substitutions of interest in the GP160 domain was identified by the next-generation sequencing (NGS) assay. Protocol defined virologic failure (PDVF) through Week 96 Population comprised of all participants with available phenotypic and genotypic resistance data meeting at the time protocol defined virologic failure (PDVF) was met. The criteria for PDVF was a) Confirmed, or last available prior to discontinuation, HIV-1 RNA >=400 c/mL at any time after prior confirmed suppression to <400 c/mL prior to Week 24 or Confirmed, or last available prior to discontinuation, > 1 log10 c/mL increase in HIV-1 RNA at any time above nadir level where nadir is >=40 c/mL prior to Week 24. b) Confirmed, or last available prior to discontinuation, HIV-1 RNA >=400 c/mL at or after Week 24.	Week 96
Number of Participants With Indicated Fold Change Ratio (FCR) Using the Monogram PhenoSense Entry Assay-Randomized Cohort	The phenotypic resistance to a drug is defined in terms of a fold change (FC) in IC50s, i.e., the ratio of the 50% inhibitory concentration (IC50) of the clinical isolate to the IC50 of a reference strain (wild type control). FCR was calculated as FC at PDVF divided by Baseline FC. The number of participants with the indicated change (ratio) in the two values at the time of PDVF is presented. FCR<1 indicates that FC is smaller on-treatment than at Baseline. FCR >3 indicates that on-treatment FC is 3 times greater than it was at Baseline.	Week 96

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Investigators: Study Director: GSK Clinical Trials, ViiV Healthcare

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2015
• Primary Completion (Actual): August 18, 2016
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: February 9, 2015
• First Submitted That Met QC Criteria: February 12, 2015
• First Posted (Estimated): February 13, 2015

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; Fostemsavir
• Other Study ID Numbers: 205888; AI438-047 (Other Identifier: Bristol-Myers Squibb); 2014-002111-41 (EudraCT Number)