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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02049138




Registration number
NCT02049138
Ethics application status
Date submitted
28/01/2014
Date registered
30/01/2014

Titles & IDs
Public title
An Open-label Extension Study Evaluating the Safety and Efficacy of Upadacitinib (ABT-494) in Adults With Rheumatoid Arthritis
Scientific title
Phase 2 Study, Multicenter, Open-Label Extension (OLE) Study in Rheumatoid Arthritis Subjects Who Have Completed a Preceding Phase 2 Randomized Controlled Trial (RCT) With Upadacitinib (ABT-494)
Secondary ID [1] 0 0
2013-003530-33
Secondary ID [2] 0 0
M13-538
Universal Trial Number (UTN)
Trial acronym
BALANCE-EXTEND
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 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 - Upadacitinib
Treatment: Other - Pneumococcal 13-valent conjugate vaccine (PCV-13)

Experimental: Upadacitinib - Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). Participants who did not achieve a 20% improvement from RCT Baseline in both Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 6 or Week 12 were up-titrated to 12 mg BID. From January 2017 participants were transitioned to a once-daily (QD) regimen of upadacitinib, either 15 mg QD (participants who were taking 6 mg BID) or 30 mg QD (participants taking 12 mg BID). Starting with Protocol Amendment 5 participants receiving 30 mg QD upadacitinib had the option to decrease the dose to 15 mg QD at the investigator's discretion.

A subset of participants who opted-in to the vaccine substudy received a single-dose of 0.5 mL intramuscular injection of pneumococcal 13-valent conjugate vaccine (PCV-13).


Treatment: Drugs: Upadacitinib
Tablet taken orally

Treatment: Other: Pneumococcal 13-valent conjugate vaccine (PCV-13)
Administered by intramuscular injection

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

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response Over Time
Timepoint [1] 0 0
Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Primary outcome [2] 0 0
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response Over Time
Timepoint [2] 0 0
Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Primary outcome [3] 0 0
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response Over Time
Timepoint [3] 0 0
Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Primary outcome [4] 0 0
Percentage of Participants With Satisfactory Humoral Response to PCV-13 Four Weeks After Vaccination
Timepoint [4] 0 0
Vaccination Baseline (defined as the last non-missing observation on or before the date of receiving PCV-13 vaccination) and 4 weeks after vaccination
Secondary outcome [1] 0 0
Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score-28 (DAS28[CRP]) Over Time
Timepoint [1] 0 0
Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [2] 0 0
Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score-28 (DAS28[CRP]) Over Time
Timepoint [2] 0 0
Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [3] 0 0
Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Over Time
Timepoint [3] 0 0
Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [4] 0 0
Percentage of Participants Achieving Clinical Remission (CR) Based on Clinical Disease Activity Index (CDAI) Over Time
Timepoint [4] 0 0
Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [5] 0 0
Percentage of Participants Achieving Low Disease Activity (LDA) Based on Simplified Disease Activity Index (SDAI) Over Time
Timepoint [5] 0 0
Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [6] 0 0
Percentage of Participants Achieving Clinical Remission (CR) Based on Simplified Disease Activity Index (SDAI) Over Time
Timepoint [6] 0 0
Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [7] 0 0
Change From Baseline in Disease Activity Score Based on CRP (DAS28 [CRP]) Over Time
Timepoint [7] 0 0
Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [8] 0 0
Change From Baseline in Clinical Disease Activity Index (CDAI) Over Time
Timepoint [8] 0 0
Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [9] 0 0
Change From Baseline in SimplifiedDisease Activity Index (SDAI) Over Time
Timepoint [9] 0 0
Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [10] 0 0
Change From Baseline in Tender Joint Count (TJC68) Over Time
Timepoint [10] 0 0
Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [11] 0 0
Change From Baseline in Swollen Joint Count (SJC66) Over Time
Timepoint [11] 0 0
Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [12] 0 0
Change From Baseline in Physician's Global Assessment of Disease Activity Over Time
Timepoint [12] 0 0
Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [13] 0 0
Change From Baseline in Patient's Global Assessment of Disease Activity Over Time
Timepoint [13] 0 0
Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [14] 0 0
Change From Baseline in Patient's Assessment of Pain Over Time
Timepoint [14] 0 0
Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [15] 0 0
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Over Time
Timepoint [15] 0 0
Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [16] 0 0
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) Over Time
Timepoint [16] 0 0
Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [17] 0 0
Change From Baseline in in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Over Time
Timepoint [17] 0 0
Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [18] 0 0
Change From Baseline in Work Instability Scale for RA (RA-WIS) Over Time
Timepoint [18] 0 0
Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [19] 0 0
Change From Baseline in EuroQoL-5D (EQ-5D) Index Over Time
Timepoint [19] 0 0
Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [20] 0 0
Change From Baseline in EuroQoL-5D VAS Score Over Time
Timepoint [20] 0 0
Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Secondary outcome [21] 0 0
Percentage of Participants With Satisfactory Humoral Response to PCV-13 12 Weeks After Vaccination
Timepoint [21] 0 0
Vaccination Baseline and 12 weeks after vaccination
Secondary outcome [22] 0 0
Geometric Mean Fold Rise (GMFR) of Anti-pneumococcal Antibody Levels to Each of the 12 Pneumococcal Antigens 4 and 12 Weeks After Vaccination
Timepoint [22] 0 0
Vaccination Baseline and 4 and 12 weeks after vaccination

Eligibility
Key inclusion criteria
1. Subjects who have completed Study M13-550 (NCT01960855) or Study M13-537 (NCT02066389) with upadacitinib (ABT-494) and did not develop any discontinuation criteria.
2. If the subject has evidence of new latent tuberculosis (TB) infection, the subject must initiate and complete a minimum of 2 weeks (or per local guidelines, whichever is longer) of an ongoing TB prophylaxis before continuing to receive study drug.
3. If female, subject must be postmenopausal, OR permanently surgically sterile, OR for women of childbearing potential practicing at least one protocol-specified method of birth control, that is effective from Study Day 1 through at least 30 days after the last dose of study drug.
4. Subjects must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures.

Substudy:

1. Must currently be enrolled in the main study.
2. Must have been receiving a stable dose of upadacitinib (either 15 mg QD or 30 mg QD) for a minimum of 4 weeks prior to the Vaccination visit.
3. Must have been on a stable dose of background methotrexate (no change in dose or frequency) for a minimum of 4 weeks prior to the Vaccination visit.
4. If subject is on corticosteroids, must remain on a stable dose of = 10 mg/day of prednisone or equivalent corticosteroid therapy for at least 4 weeks after the vaccination visit.
5. Must meet the prescribing specifications as per local label requirements to receive Prevnar 13® vaccine.
6. Willing to receive Prevnar13® vaccine.
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnant or breastfeeding female.
2. Ongoing infections at Week 0 that have not been successfully treated. Subjects with ongoing infections undergoing treatment may be enrolled but not dosed until the infection has been successfully treated.
3. Anticipated requirement or receipt of any live vaccine during study participation including up to 30 days after the last dose of study drug.
4. Laboratory values from the visit immediately prior to Baseline Visit (local requirements may apply) meeting the following criteria:

* Serum aspartate transaminase (AST) or alanine transaminase (ALT) > 3.0 × upper limit of normal (ULN)
* Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 40 mL/min/1.73m^2
* Total white blood cell count (WBC) < 2,000/µL
* Absolute neutrophil count (ANC) < 1,000/µL
* Platelet count < 50,000/µL
* Absolute lymphocytes count < 500/µL
* Hemoglobin < 8 g/dL
5. Enrollment in another interventional clinical study while participating in this study.
6. Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive study drug.

Substudy:

1. Receiving any conventional synthetic disease modifying antirheumatic drugs (csDMARDs) other than methotrexate
2. Receiving > 10 mg/day of prednisone or equivalent corticosteroid therapy.
3. Receipt of any steroid injection within 4 weeks prior to Vaccination visit.
4. History of severe allergic reaction (e.g., anaphylaxis) to any component of Prevnar 13®.
5. History of any documented pneumococcal infection within the last 6 months prior to the vaccination visit.
6. Receipt of any vaccine 4 weeks prior to the vaccination visit and/or anticipation of any vaccination for 4 weeks after the vaccination visit.
7. Receipt of any pneumococcal vaccine.
8. Subject is not suitable for the sub-study as per the Investigator's judgment.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
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)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
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 Mexico
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
South Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
West Virginia
Country [22] 0 0
United States of America
State/province [22] 0 0
Wisconsin
Country [23] 0 0
Belgium
State/province [23] 0 0
Bruxelles-Capitale
Country [24] 0 0
Belgium
State/province [24] 0 0
Genk
Country [25] 0 0
Bulgaria
State/province [25] 0 0
Plovdiv
Country [26] 0 0
Bulgaria
State/province [26] 0 0
Sofia
Country [27] 0 0
Bulgaria
State/province [27] 0 0
Varna
Country [28] 0 0
Chile
State/province [28] 0 0
Los Lagos
Country [29] 0 0
Czechia
State/province [29] 0 0
Ostrava
Country [30] 0 0
Czechia
State/province [30] 0 0
Petrkovice
Country [31] 0 0
Czechia
State/province [31] 0 0
Praha
Country [32] 0 0
Czechia
State/province [32] 0 0
Prostejov
Country [33] 0 0
Hungary
State/province [33] 0 0
Pest
Country [34] 0 0
Hungary
State/province [34] 0 0
Budapest
Country [35] 0 0
Hungary
State/province [35] 0 0
Szolnok
Country [36] 0 0
Hungary
State/province [36] 0 0
Veszprem
Country [37] 0 0
Israel
State/province [37] 0 0
Tel-Aviv
Country [38] 0 0
Israel
State/province [38] 0 0
Ashkelon
Country [39] 0 0
Latvia
State/province [39] 0 0
Adazi
Country [40] 0 0
Latvia
State/province [40] 0 0
Baldone
Country [41] 0 0
Latvia
State/province [41] 0 0
Riga
Country [42] 0 0
Mexico
State/province [42] 0 0
Ciudad De Mexico
Country [43] 0 0
Mexico
State/province [43] 0 0
Mexico City
Country [44] 0 0
New Zealand
State/province [44] 0 0
Canterbury
Country [45] 0 0
New Zealand
State/province [45] 0 0
Waikato
Country [46] 0 0
New Zealand
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Nelson
Country [47] 0 0
Poland
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Dolnoslaskie
Country [48] 0 0
Poland
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Lubuskie
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Poland
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Malopolskie
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Poland
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Mazowieckie
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Poland
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Podlaskie
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Poland
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Pomorskie
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Poland
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Warminsko-mazurskie
Country [54] 0 0
Poland
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Wielkopolskie
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Poland
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Lublin
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Puerto Rico
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Carolina
Country [57] 0 0
Puerto Rico
State/province [57] 0 0
San Juan
Country [58] 0 0
Russian Federation
State/province [58] 0 0
Tatarstan, Respublika
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Tverskaya Oblast
Country [60] 0 0
Russian Federation
State/province [60] 0 0
Sankt-Peterburg
Country [61] 0 0
Slovakia
State/province [61] 0 0
Martin
Country [62] 0 0
Slovakia
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Senica
Country [63] 0 0
South Africa
State/province [63] 0 0
Western Cape
Country [64] 0 0
Spain
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A Coruna
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Spain
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Alicante
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Spain
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Madrid
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Spain
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Malaga
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Spain
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Barcelona
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Spain
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Sevilla
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Ukraine
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Kiev
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Ukraine
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Kyiv
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United Kingdom
State/province [72] 0 0
Cheshire West And Chester
Country [73] 0 0
United Kingdom
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London, City Of
Country [74] 0 0
United Kingdom
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Suffolk
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Leeds

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
For details on when studies are available for sharing, please refer to the link below.
Available to whom?
Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Use Agreement (DUA). For more information on the process, or to submit a request, visit the following link.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/abbvie/


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.