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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02362503




Registration number
NCT02362503
Ethics application status
Date submitted
9/02/2015
Date registered
13/02/2015
Date last updated
17/02/2020

Titles & IDs
Public title
Attachment Inhibitor Comparison in Heavily Treatment Experienced Patients
Scientific 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)
Secondary ID [1] 0 0
AI438-047
Secondary ID [2] 0 0
205888
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BMS-663068
Other interventions - Placebo

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.

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.

Experimental: BMS-663068 - BMS-663068 600 mg tablets orally twice daily for 48 weeks or longer.


Treatment: Drugs: BMS-663068
BMS-663068

Other interventions: Placebo
Placebo

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Day 1 and Day 8
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Day 1 and Day 8
Secondary outcome [2] 0 0
Percentage of Participants With HIV-1 RNA <40 c/mL at Weeks 24 and 48-Randomized Cohort - The durability of response (that is, the number of participants achieving HIV-1 RNA <40 c/mL) at Weeks 24 and 48 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 and 48 or those who changed OBT due to lack of efficacy through Weeks 24 and 48 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 and 48 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.
Timepoint [2] 0 0
Weeks 24 and 48
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Up to Week 48 analysis cut-off date
Secondary outcome [4] 0 0
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. Only participants with data available at the specified time points were analyzed (represented by n=X in category titles). 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.
Timepoint [4] 0 0
Baseline and up to Week 48 analysis cut-off date
Secondary outcome [5] 0 0
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. Only participants with data available at the specified time points were analyzed (represented by n=X in category titles). 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.
Timepoint [5] 0 0
Baseline and up to Week 48 analysis cut-off date
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Up to Week 48 analysis cut-off date
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Day 1 and Day 8
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Day 1 and Day 8
Secondary outcome [9] 0 0
Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 48-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. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles). 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.
Timepoint [9] 0 0
Baseline and up to Week 48
Secondary outcome [10] 0 0
Change From Baseline in CD4+ T- Cell Count Through Week 48-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. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles). 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.
Timepoint [10] 0 0
Baseline and up to Week 48
Secondary outcome [11] 0 0
Change From Baseline in CD4+ T- Cell Count Percentage Through Week 48 - 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. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles). 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.
Timepoint [11] 0 0
Baseline and up to Week 48
Secondary outcome [12] 0 0
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 drug resistance testing. Participants with emergent viral genotypic substitutions of interest in GP160 domain was identified by next-generation sequencing (NGS) assay. Virologic failure (VF) Population comprised of all participants with available phenotypic and genotypic resistance data meeting at the time protocol defined virologic failure (PDVF) was met. 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. All participants received fostemsavir during open-label period irrespective of original randomization; hence, combined totals for Randomized Cohort is presented.
Timepoint [12] 0 0
Week 48
Secondary outcome [13] 0 0
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, ie, 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. All the participants received fostemsavir during open-label period irrespective of the original arms to which they were randomized; hence, combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.
Timepoint [13] 0 0
Week 48

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Darlinghurst
Recruitment hospital [2] 0 0
GSK Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
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United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Oklahoma
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
Argentina
State/province [19] 0 0
Buenos Aires
Country [20] 0 0
Argentina
State/province [20] 0 0
Córdova
Country [21] 0 0
Argentina
State/province [21] 0 0
Rosario
Country [22] 0 0
Belgium
State/province [22] 0 0
Antwerpen
Country [23] 0 0
Belgium
State/province [23] 0 0
Brussels
Country [24] 0 0
Brazil
State/province [24] 0 0
Paraná
Country [25] 0 0
Brazil
State/province [25] 0 0
Rio Grande Do Sul
Country [26] 0 0
Brazil
State/province [26] 0 0
São Paulo
Country [27] 0 0
Brazil
State/province [27] 0 0
Belo Horizonte
Country [28] 0 0
Brazil
State/province [28] 0 0
Ribeirao Preto
Country [29] 0 0
Brazil
State/province [29] 0 0
Rio de Janeiro
Country [30] 0 0
Brazil
State/province [30] 0 0
Salvador
Country [31] 0 0
Canada
State/province [31] 0 0
British Columbia
Country [32] 0 0
Canada
State/province [32] 0 0
Ontario
Country [33] 0 0
Canada
State/province [33] 0 0
Quebec
Country [34] 0 0
Canada
State/province [34] 0 0
Vancouver
Country [35] 0 0
Chile
State/province [35] 0 0
Región Metro De Santiago
Country [36] 0 0
Chile
State/province [36] 0 0
Santiago
Country [37] 0 0
Chile
State/province [37] 0 0
Temuco
Country [38] 0 0
Colombia
State/province [38] 0 0
Bogota
Country [39] 0 0
Colombia
State/province [39] 0 0
Bogotá
Country [40] 0 0
Colombia
State/province [40] 0 0
Cali, Valle Del Cauca
Country [41] 0 0
France
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Bordeaux cedex
Country [42] 0 0
France
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Marseille
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France
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Nantes
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France
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Paris Cedex 12
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France
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Paris
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Germany
State/province [46] 0 0
Baden-Wuerttemberg
Country [47] 0 0
Germany
State/province [47] 0 0
Hessen
Country [48] 0 0
Germany
State/province [48] 0 0
Nordrhein-Westfalen
Country [49] 0 0
Germany
State/province [49] 0 0
Berlin
Country [50] 0 0
Germany
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München
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Greece
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Athens
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Greece
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Thessaloniki
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Ireland
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Dublin
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Italy
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Lazio
Country [55] 0 0
Italy
State/province [55] 0 0
Lombardia
Country [56] 0 0
Italy
State/province [56] 0 0
Piemonte
Country [57] 0 0
Italy
State/province [57] 0 0
Modena
Country [58] 0 0
Italy
State/province [58] 0 0
Monza
Country [59] 0 0
Mexico
State/province [59] 0 0
Estado De México
Country [60] 0 0
Mexico
State/province [60] 0 0
Jalisco
Country [61] 0 0
Mexico
State/province [61] 0 0
Chihuahua
Country [62] 0 0
Mexico
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Ciudad de Mexico
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Mexico
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Distrito Federal
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Netherlands
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Utrecht
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Peru
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Loreto
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Peru
State/province [66] 0 0
Lima
Country [67] 0 0
Poland
State/province [67] 0 0
Szczecin
Country [68] 0 0
Poland
State/province [68] 0 0
Warszawa
Country [69] 0 0
Poland
State/province [69] 0 0
Wroclaw
Country [70] 0 0
Portugal
State/province [70] 0 0
Lisboa
Country [71] 0 0
Portugal
State/province [71] 0 0
Lisbon
Country [72] 0 0
Puerto Rico
State/province [72] 0 0
San Juan
Country [73] 0 0
Romania
State/province [73] 0 0
Bucharest
Country [74] 0 0
Russian Federation
State/province [74] 0 0
Irkutsk
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Krasnodar
Country [76] 0 0
South Africa
State/province [76] 0 0
Eastern Cape
Country [77] 0 0
South Africa
State/province [77] 0 0
Free State
Country [78] 0 0
South Africa
State/province [78] 0 0
Gauteng
Country [79] 0 0
South Africa
State/province [79] 0 0
KwaZulu- Natal
Country [80] 0 0
South Africa
State/province [80] 0 0
Western Province
Country [81] 0 0
South Africa
State/province [81] 0 0
Cape Town
Country [82] 0 0
South Africa
State/province [82] 0 0
Durban
Country [83] 0 0
Spain
State/province [83] 0 0
Badalona, Barcelona
Country [84] 0 0
Spain
State/province [84] 0 0
Barcelona
Country [85] 0 0
Spain
State/province [85] 0 0
Madrid
Country [86] 0 0
Spain
State/province [86] 0 0
Seville, Sevilla
Country [87] 0 0
Taiwan
State/province [87] 0 0
Taipei
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Bournemouth
Country [89] 0 0
United Kingdom
State/province [89] 0 0
Leicestershire
Country [90] 0 0
United Kingdom
State/province [90] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ViiV Healthcare
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02362503
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
ViiV Healthcare
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications