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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00559585




Registration number
NCT00559585
Ethics application status
Date submitted
15/11/2007
Date registered
16/11/2007
Date last updated
9/11/2015

Titles & IDs
Public title
Methotrexate-Inadequate Response Study
Scientific title
A Phase IIIB Multicenter, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Abatacept Administered Subcutaneously and Intravenously in Subjects With Rheumatoid Arthritis, Receiving Background Methotrexate, and Experiencing an Inadequate Response to Methotrexate
Secondary ID [1] 0 0
EUDRACT # 2007-005434-37
Secondary ID [2] 0 0
IM101-174
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis (RA) 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Subcutaneous (SC) Abatacept
Treatment: Drugs - Intravenous (IV) Abatacept

Active comparator: Subcutaneous (SC) Abatacept - Participants received 125 mg weekly SC abatacept injections (with an intravenous \[IV\] abatacept loading dose on Day 1, based on weight). A double-dummy design was used to protect the blind, thus, participants also received IV injections of placebo (IV Placebo) with the exception that on Day 1 a loading dose of IV abatacept replaced the IV Placebo treatment.

Active comparator: Intravenous (IV) Abatacept - Participants received IV abatacept infusions on Days 1, 15, 29, and every 28 days, thereafter. A double-dummy design was used to protect the blind, thus, participants also received SC injections of placebo (SC Placebo).


Treatment: Drugs: Subcutaneous (SC) Abatacept
Participants received 125 mg weekly SC abatacept injections (with an intravenous \[IV\] abatacept loading dose on Day 1, based on weight). A double-dummy design was used to protect the blind, thus, participants also received IV injections of placebo (IV Placebo) with the exception that on Day 1 a loading dose of IV abatacept replaced the IV Placebo treatment.

Treatment: Drugs: Intravenous (IV) Abatacept
Participants received IV abatacept infusions on Days 1, 15, 29, and every 28 days, thereafter. A double-dummy design was used to protect the blind, thus, participants also received SC injections of placebo (SC Placebo).

500mg (for body weight up to 60 kg)

750 mg (body weight between 61 and 100 kg)

1g (body weight above 100 kg)infusions

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

Outcomes
Primary outcome [1] 0 0
Double-blind Period: Number of Participants Achieving American College of Rheumatology (ACR) 20 Response at Day 169
Timepoint [1] 0 0
Day 169
Primary outcome [2] 0 0
Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population
Timepoint [2] 0 0
Days 85, and 169 and postvisits on Days 28, 56, and 85
Secondary outcome [1] 0 0
Double-blind Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Day 169
Timepoint [1] 0 0
Day 169
Secondary outcome [2] 0 0
Double-blind Period: Mean Baseline Health Assessment Questionnaire Disability Index (HAQ-DI) for Participants With Assessments at Day 169
Timepoint [2] 0 0
Day 169
Secondary outcome [3] 0 0
Double-blind Period: Adjusted Mean Change From Baseline to Day 169 in HAQ-DI
Timepoint [3] 0 0
Baseline to Day 169
Secondary outcome [4] 0 0
Double-blind Period: Number of Participants Achieving Clinically Meaningful HAQ-DI Response at Day 169
Timepoint [4] 0 0
Day 169
Secondary outcome [5] 0 0
Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation
Timepoint [5] 0 0
Day 1 to 56 days after last dose in short-term or first dose in the long-term, whichever occurs first.
Secondary outcome [6] 0 0
Anti-TNF Failure Sub-study Double-blind Period: Number of Participants With SAEs, AEs Leading to Discontinuation or Who Died
Timepoint [6] 0 0
Day 1 to 56 days after last dose in short-term or first dose in the long-term, whichever occurs first.
Secondary outcome [7] 0 0
Double-blind Period: Number of Participants With AEs of Special Interest
Timepoint [7] 0 0
Day 1 up to 56 days post last dose in short- term period or first dose in the long -term period, whichever occurs first.
Secondary outcome [8] 0 0
Double-blind Period: Number of Participants With Clinically Significant Abnormalities in Vital Sign Measurements
Timepoint [8] 0 0
Day 1 through end of short-term period (Day 169)
Secondary outcome [9] 0 0
Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality
Timepoint [9] 0 0
Day 1 through end of short-term period (Day 169)
Secondary outcome [10] 0 0
Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality
Timepoint [10] 0 0
Day 1 through end of short-term period (Day 169)
Secondary outcome [11] 0 0
Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality
Timepoint [11] 0 0
Day 1 through end of short-term period (Day 169)
Secondary outcome [12] 0 0
Double-blind Period: Minimum Observed Serum Concentration of Abatacept
Timepoint [12] 0 0
Days 57, 85, 113, 120, 127, 134, 141, and 169
Secondary outcome [13] 0 0
Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept
Timepoint [13] 0 0
Days 57, 85, 113, 120, 127, 134, 141, and 169 (ST Period)
Secondary outcome [14] 0 0
Double-blind Period: Maximum Observed Serum Concentration of Abatacept
Timepoint [14] 0 0
End of infusion on Days 1 and 113 for IV infusion and in the dosing interval of Days 113 to 120 for subcutaneous
Secondary outcome [15] 0 0
Anti-TNF Failure Substudy Double Blind Period: Geometric Mean Maximum Observed Serum Concentration of Abatacept
Timepoint [15] 0 0
End of infusion on Days 1 and 113 for IV infusion and in the dosing interval of Days 113 to 120 for subcutaneous
Secondary outcome [16] 0 0
Double-blind Period: Area Under The Curve In A Dose Interval (AUC TAU) of Abatacept
Timepoint [16] 0 0
Dosing interval between Days 113 and 141 (TAU=28 days)
Secondary outcome [17] 0 0
Anti-TNF Failure Sub-study Double Blind Period: Area Under The Curve In A Dose Interval (AUC TAU) of Abatacept
Timepoint [17] 0 0
Dosing Interval between Days 113 and 141 (TAU=28 days)
Secondary outcome [18] 0 0
Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA)
Timepoint [18] 0 0
Days 85, and 169 and postvisits on Days 28, 56, and 85
Secondary outcome [19] 0 0
Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period
Timepoint [19] 0 0
Baseline to Days 15, 29, 57, 85, 113, 141, and 169
Secondary outcome [20] 0 0
Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized
Timepoint [20] 0 0
Days 85, and 169 and postvisits on Days 28, 56, and 85
Secondary outcome [21] 0 0
Double-blind Period: Number of Participants Seroconverting by Day 169 According to Status (Negative or Positive) at Baseline
Timepoint [21] 0 0
Baseline to Day 169
Secondary outcome [22] 0 0
Open-Label LT Period: Number of Participants Achieving ACR 20 Response at Days 169, 729, 1261, and 1821
Timepoint [22] 0 0
Days 169, 729, 1261, 1821
Secondary outcome [23] 0 0
Open-Label LT Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Days 169, 729, 1261, 1821
Timepoint [23] 0 0
Days 169, 729, 1261, 1821
Secondary outcome [24] 0 0
Open-Label LT Period: Mean Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Using C-reactive Protein (CRP) at Days 169, 729, 1261, 1821
Timepoint [24] 0 0
Days 169, 729, 1261, 1821
Secondary outcome [25] 0 0
Open-Label LT Period: Number of Participants Achieving DAS 28 Remission at Days 169, 729, 1261, 1821
Timepoint [25] 0 0
Days 169, 729, 1261, 1821
Secondary outcome [26] 0 0
Open-Label LT Period: Number of Participants Achieving DAS 28 Low Disease Activity (LDA) at Days 169, 729, 1261, 1821
Timepoint [26] 0 0
Days 169, 729, 1261, 1821
Secondary outcome [27] 0 0
Open-Label LT Period: Number of Participants With HAQ-DI Response at Days 169, 729, 1261, 1821
Timepoint [27] 0 0
Days 169, 729, 1261, 1821
Secondary outcome [28] 0 0
Open-Label LT Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation
Timepoint [28] 0 0
End of ST Period (Day 169) to last dose plus 85 days, up to 5 years (September 2014)
Secondary outcome [29] 0 0
Open-Label LT Period: Number of Participants With AEs of Special Interest
Timepoint [29] 0 0
End of ST Period (Day 169) to last dose plus 85 days, up to 5 years (September 2014)
Secondary outcome [30] 0 0
Open-Label LT Period: Number of Participants With Clinically Significant Abnormalities in Vital Sign Measurements
Timepoint [30] 0 0
End of ST Period (Day 169) to last dose plus 7 days, up to 5 years (September 2014)
Secondary outcome [31] 0 0
Open-Label LT Period: Number of Participants With Clinically Significant Laboratory Abnormalities
Timepoint [31] 0 0
End of ST Period (Day 169) to last dose plus 7 days, up to 5 years (September 2014)

Eligibility
Key inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com



* Subjects who are considered methotrexate inadequate responders
* 10 or more swollen joints (66 joint count) and 12 or more tender joints (68 joint count)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Subjects who failed one or multiple anti-tumor necrosis factor (TNF) therapies
* Subjects who meet diagnostic criteria for any other rheumatic disease (e.g., lupus erythematous)
* Subjects with active vasculitis of a major organ system (except for subcutaneous rheumatoid nodules)
* Subjects with severe chronic or recurrent bacterial infections
* Subjects who have received treatment with rituximab

An Anti-TNF Failure Sub-study was initiated (recruited separately from Main study) using the same treatment as the Main study in order to assess the immunogenicity and safety in the Anti-TNF Failure population. The Sub-study terminated due to low recruitment and participants were permitted to roll into the LT Open Label Period.

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 analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Local Institution - St Leonards
Recruitment hospital [2] 0 0
Local Institution - Cairns
Recruitment hospital [3] 0 0
Local Institution - Maroochydore
Recruitment hospital [4] 0 0
Local Institution - Woodville
Recruitment hospital [5] 0 0
Local Institution - Heidelberg
Recruitment hospital [6] 0 0
Local Institution - Shenton Park
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
QLD 4870 - Cairns
Recruitment postcode(s) [3] 0 0
4558 - Maroochydore
Recruitment postcode(s) [4] 0 0
5011 - Woodville
Recruitment postcode(s) [5] 0 0
3081 - Heidelberg
Recruitment postcode(s) [6] 0 0
6008 - Shenton Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
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United States of America
State/province [8] 0 0
Georgia
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Idaho
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United States of America
State/province [10] 0 0
Illinois
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State/province [11] 0 0
Maryland
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Massachusetts
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Michigan
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Mississippi
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Missouri
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Nebraska
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New Jersey
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New Mexico
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New York
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North Carolina
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Ohio
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United States of America
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Oklahoma
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Oregon
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Pennsylvania
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Tennessee
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Texas
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Virginia
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Washington
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Argentina
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Argentina
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Bruxelles
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Ontario
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Quebec
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Saskatchewan
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Chile
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Le Mans
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Lille Cedex
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Marseille
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France
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Nice Cedex 3
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France
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Paris Cedex 13
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France
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Paris Cedex 14
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France
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Poitiers
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France
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Leipzig
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Muenchen
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Gujarat
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Karnataka
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Lucknow
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Napoli
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Padova
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Pavia
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Roma
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Siena
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Daegu
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Queretaro
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Mexico
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Netherlands
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Leeuwarden
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Peru
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Callao
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Peru
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Lima
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Poland
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Bialystok
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Bydgoszcz
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Konskie
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Krakow
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Poznan
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Torun
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Warszawa
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Russian Federation
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Ekaterinburg
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Russian Federation
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Moscow
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Russian Federation
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Yaroslavl
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South Africa
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Gauteng
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South Africa
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Kwa Zulu Natal
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South Africa
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Western Cape
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Taiwan
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Kaohsiung
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Taichung
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Turkey
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Denizli
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Edirne
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Turkey
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Gaziantep
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United Kingdom
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Cambridgeshire
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United Kingdom
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Glamorgan
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United Kingdom
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Greater London
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United Kingdom
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Hampshire
Country [123] 0 0
United Kingdom
State/province [123] 0 0
Tyne And Wear

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.