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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT02814175
Registration number
NCT02814175
Ethics application status
Date submitted
21/06/2016
Date registered
27/06/2016
Titles & IDs
Public title
A Study of Subjects With Psoriatic Arthritis to Investigate the Effectiveness of Adalimumab Introduction Compared With Methotrexate Dose Escalation (CONTROL)
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Scientific title
A Phase 4 Open-label Randomized Controlled Study COmparing the Effectiveness of Adalimumab iNTROduction and Methotrexate Dose escaLation in Subjects With Psoriatic Arthritis (CONTROL)
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Secondary ID [1]
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2016-000191-21
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Secondary ID [2]
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M14-496
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Universal Trial Number (UTN)
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Trial acronym
CONTROL
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Psoriatic Arthritis
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Condition category
Condition code
Musculoskeletal
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Osteoarthritis
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Inflammatory and Immune System
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Rheumatoid arthritis
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Inflammatory and Immune System
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Other inflammatory or immune system disorders
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Musculoskeletal
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Other muscular and skeletal disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Active comparator: Part 1: MTX Escalated Dose - Methotrexate (MTX) escalated to 20 - 25 mg or highest tolerable dose every week (ew)
Experimental: Part 1: ADA + MTX - Adalimumab (ADA) 40 mg every other week (eow) in combination with MTX 15 mg ew
Active comparator: Part 2: MTX Escalated Dose - Participants achieving minimal disease activity (MDA) at Week 16 on MTX escalated to 20 -25 mg or highest tolerable dose ew, continued with the same MTX dose
Active comparator: Part 2: ADA + MTX Escalated Dose - Participants not achieving MDA at Week 16 on MTX escalated to 20 - 25 mg or highest tolerable dose ew, received ADA 40 mg eow in combination with MTX 20 - 25 mg or highest tolerable dose ew
Experimental: Part 2: ADA - Participants achieving MDA at Week 16 on ADA 40 mg eow plus MTX 15 mg ew, had MTX completely withdrawn at Week 16 and continued receiving ADA as monotherapy
Experimental: Part 2: ADA ew + MTX - Participants not achieving MDA at Week 16 on ADA 40 mg eow plus MTX 15 mg ew, had ADA escalated to 40 mg ew in combination with MTX 15 mg ew
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Percentage of Participants Achieving Minimal Disease Activity (MDA) (Non-responder Imputation [NRI]) (Part 1)
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Assessment method [1]
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Minimal disease activity (MDA) for psoriatic arthritis (PsA) was defined as fulfilling at least 5 of the following 7 criteria: tender and swollen joint counts (TJC) = 1 (out of TJC68 assessed in this study), swollen joint count (SJC) = 1 (out of SJC66 assessed in this study), Psoriasis Area and Severity Index (PASI) = 1 or body surface area (BSA) = 3; Patient's assessment of pain visual analogue scale (VAS) = 15, Patient's global assessment of disease activity (PtGA) VAS = 20, Health Assessment Questionnaire Disability Index (HAQ-DI) score = 0.5, and tender entheseal points = 1 (out of 8 assessed in this study).
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Timepoint [1]
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Week 16
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Secondary outcome [1]
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Change in Dermatology Life Quality Index (DLQI) Score From Baseline (Part 1)
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Assessment method [1]
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The Dermatology Life Quality Index (DLQI) score is a measure of participant's quality of life (QOL) related to skin disease.The DLQI questionnaire consists of 10 questions concerning participants' perception of the impact of skin diseases on different aspects of their health related QOL over the last week. The items of the DLQI encompass aspects such as symptoms and feelings, daily activities, leisure, work or school, personal relationships and the side effects of treatment. The range of possible DLQI scores is 0 to 30, with a score of 0 indicating no effect at all on a participant's life and a score of 30 indicating extremely large effect on participant's life. A decrease in DLQI score indicates improvement.
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Timepoint [1]
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From Day 1 to Week 16
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Secondary outcome [2]
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Change in Tender Dactylitic Digit Count From Baseline for Participants With Presence of Dactylitis at Baseline (Part 1)
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Assessment method [2]
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Hands and feet bilaterally were assessed for the presence/absence of dactylitis and associated tenderness for participants with presence of dactylitis at baseline. The tender dactylitic digit count is equal to the number of swollen and painful digits (range 0 to 20). A decrease indicates improvement.
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Timepoint [2]
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From Day 1 to Week 16
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Secondary outcome [3]
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Change in Disease Activity Score 28 (DAS28)-C-reactive Protein (CRP) Score From Baseline (Part 1)
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Assessment method [3]
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The Disease Activity Score 28 (DAS28) is a validated index of rheumatoid arthritis disease activity but is also used in PsA clinical trials. DAS28 is a composite score calculated using a mathematical formula based on the scores for these scales. DAS28 includes tender and swollen joint counts, PtGA, and acute phase reactant (CRP in this study). DAS28 scores range from 0 to 10, with higher scores indicating more disease activity. A larger negative change in the DAS28 score indicates greater improvement.
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Timepoint [3]
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From Day 1 to Week 16
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Secondary outcome [4]
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Change in Psoriatic Arthritis Impact of Disease Score (PsAID) Score From Baseline (Part 1)
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Assessment method [4]
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Psoriatic Arthritis Impact of Disease Score (PsAID) was developed by an European League Against Rheumatism (EULAR) initiative and is a validated patient self-reported tool to assess the impact of PsA on the participant's life. The PsAID is a composite score calculated using a mathematical formula based on the scores for each component. PsAID-9 was developed for clinical trials and was used in this study. The PsAID-9 is calculated based on 9 Numerical rating scales (NRS) questions that include pain, fatigue, skin, work and/or leisure activities, function, discomfort, sleep, coping, and anxiety). Each NRS is assessed as a number between 0 and 10. PsAID scores range from 0 to 10, with higher scores indicating worse status. A larger negative change in the PsAID-9 score indicates greater improvement.
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Timepoint [4]
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From Day 1 to Week 16
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Secondary outcome [5]
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Percentage of Participants Achieving American College of Rheumatology (ACR) 20/50/70 Response (Part 1)
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Assessment method [5]
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The ACR is a standard criteria originally developed to measure the effectiveness of various arthritis medications or treatments in clinical trials for RA, but is also widely used in PsA. The ACR measures improvement in tender joint count (TJC) or swollen joint count (SJC), and improvement in at least 3 of the following 5 parameters: Patient Global Assessment (PtGA), Physician's Global Assessment of Disease Activity (PhGA), physical function (using HAQ-DI) and acute phase reactant (using CRP). ACR 20/50/70 response is achieved if = 20%/= 50%/= 70% improvement in tender joint count (TJC) or swollen joint count (SJC) as well as a = 20%/= 50%/= 70% improvement in = 3 of the other 5 parameters.
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Timepoint [5]
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Week 16
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Secondary outcome [6]
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Change in Leeds Enthesitis Index (LEI) From Baseline (Part 1) for Participants With Presence of LEI at Baseline
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Assessment method [6]
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The Leeds Enthesitis Index (LEI) is an enthesitis measure developed specifically for PsA and assesses the presence or absence of tenderness at the following 3 bilateral enthesial sites: medial femoral condyles, lateral epicondyles of the humerus, and Achilles tendon insertions for participants with presence of LEI at baseline.Tenderness on examination is recorded as either present (1) or absent (0) for each of the 6 sites, for an overall score range of 0 to 6. A decrease in LEI indicates improvement.
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Timepoint [6]
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From Day 1 to Week 16
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Secondary outcome [7]
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Percentage of Participants in MDA in Part 2 of the Study (Week 32)
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Assessment method [7]
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MDA for PsA was defined as fulfilling at least 5 of the following 7 criteria: TJC = 1 (out of TJC68 assessed in this study), SJC = 1 (out of SJC66 assessed in this study), PASI = 1 or BSA = 3; Patient's assessment of pain VAS = 15, PtGA VAS = 20, HAQ-DI score = 0.5, and tender entheseal points = 1 (out of 8 assessed in this study).
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Timepoint [7]
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Week 32
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Secondary outcome [8]
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Change in Psoriatic Arthritis Disease Activity Score (PASDAS) From Baseline (Part 1)
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Assessment method [8]
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Psoriatic Arthritis Disease Activity Score (PASDAS) is a weighted disease activity measure developed specifically for PsA. It includes PhGA, PtGA, SF-36 PCS, SJC, TJC, Leeds enthesitis count, tender dactylitic count and hsCRP lab test. The PASDAS is a composite score calculated using a mathematical formula based on the scores for each component. The PASDAS is unitless, with a typical score range between 0 and 10. Smaller values on PASDAS indicate a better condition; a negative change from baseline indicates improvement.
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Timepoint [8]
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From Day 1 to week 16
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Secondary outcome [9]
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Change in Short Form Health Survey 36 (SF-36) Score From Baseline (Part 1)
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Assessment method [9]
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The Short Form Health Survey 36 (SF-36) is a generic measure to assess participant's general health/well-being (health related quality of life); short version 2 (SF-36v2) was used. SF-36 determined participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 comprise physical component of the SF-36. Scores on each item were summed and averaged (PCS; range = 0-100). Items 5-8 comprise mental component of the SF-36. Scores on each item were summed and averaged (mental component score \[MCS\]; range = 0-100). Larger values on SF-36 indicate a better condition. A positive change from Baseline in either PCS or MCS indicates improvement.
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Timepoint [9]
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From Day 1 to Week 16
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Secondary outcome [10]
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Change in HAQ-DI Score From Baseline (Part 1)
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Assessment method [10]
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The HAQ-DI is a standardized measure of physical function in arthritis. The HAQ-DI questionnaire contains 20 items divided into 8 domains that measure: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 very severe, high-dependency disability. HAQ remission indicating normal physical function is defined by HAQ-DI score of \< 0.5. Negative change from Baseline indicates improvement.
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Timepoint [10]
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From Day 1 to Week 16
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Secondary outcome [11]
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Percentage of Participants Achieving Psoriasis Area and Severity Index (PASI) 75/90/100 Response Among Participants With BSA Greater Than or Equal to 3% at Baseline (Part 1)
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Assessment method [11]
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Psoriasis Area and Severity Index (PASI) provides a quantitative assessment of psoriasis lesional burden based on the amount of body surface area involved and the degree of severity of erythema, induration, and scale, weighted by body part. The score ranges from 0 to 72, with 0 indicating no psoriasis and 72 indicating very severe psoriasis. 75/90/100 denotes greater than or equal to 75%/90%/100% improvement in PASI score. A 100% reduction is considered complete clearance of psoriasis.
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Timepoint [11]
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Week 16
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Secondary outcome [12]
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Change in Disease Activity in Psoriatic Arthritis Score (DAPSA) Score From Baseline (Part 1)
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Assessment method [12]
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Disease Activity in Psoriatic Arthritis Score (DAPSA) score is a the sum of swollen joint count (66 joints), tender joint count (68 joints), CRP (mg/dL), Patient's Assessment of Pain (on a 10-unit VAS;0=no pain, 10=worst possible pain), and Patient's Global Assessment of Disease Activity (arthritis, on a 10-unit VAS; 0 to 100 centimeter \[cm\] VAS, 0=excellent and 10=poor). Change from baseline in DAPSA measures the change in disease activity, where a negative change indicates an improvement and a positive change indicates worsening of disease activity.
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Timepoint [12]
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From Day 1 to Week 16
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Eligibility
Key inclusion criteria
1. PsA diagnosis established at least 4 weeks prior to the date of the Screening visit and confirmed by ClASsification of Psoriatic Arthritis (CASPAR) criteria
2. Not in MDA at the time of screening
3. Has 3 or more tender and 3 or more swollen joints
4. Treated with methotrexate 15 mg (weekly) for at least 4 weeks
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1. Contraindications to adalimumab therapy and/or known hypersensitivity to adalimumab or its excipients
2. History of methotrexate intolerance/toxicity
3. Medical conditions(s) precluding methotrexate dose increase above 15 mg
4. Had prior exposure to any tumor necrosis factor (TNF) inhibitor, other mechanism of action biologic DMARD (bDMARD) or any systemic biologic agent in general
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 4
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
5/08/2016
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
19/03/2020
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Sample size
Target
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Accrual to date
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Final
246
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Recruitment in Australia
Recruitment state(s)
NSW,VIC
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Recruitment hospital [1]
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Royal Prince Alfred Hospital /ID# 153144 - Camperdown
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Recruitment hospital [2]
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Optimus Clinical Research Pty. /ID# 153145 - Kogarah
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Recruitment hospital [3]
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Liverpool Hospital /ID# 153147 - Liverpool
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Recruitment hospital [4]
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BJC Health /ID# 153875 - Paramatta
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Recruitment hospital [5]
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Box Hill Hospital /ID# 153146 - Melbourne
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Recruitment postcode(s) [1]
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2050 - Camperdown
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Recruitment postcode(s) [2]
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2217 - Kogarah
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Recruitment postcode(s) [3]
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2170 - Liverpool
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Recruitment postcode(s) [4]
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2150 - Paramatta
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Recruitment postcode(s) [5]
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3128 - Melbourne
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Recruitment outside Australia
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United States of America
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State/province [1]
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Arizona
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Florida
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Illinois
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Louisiana
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Massachusetts
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Michigan
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North Carolina
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Pennsylvania
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Washington
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United States of America
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West Virginia
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Brazil
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Rio Grande Do Sul
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Brazil
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Sao Paulo
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Bulgaria
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Plovdiv
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Bulgaria
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Sofia
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Manitoba
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Canada
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Newfoundland and Labrador
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Canada
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Ontario
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Canada
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Quebec
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Colombia
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Bogota
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Colombia
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Medellin
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Czechia
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Jihlava
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Czechia
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Praha 4
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Germany
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Baden-Wuerttemberg
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Germany
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Niedersachsen
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Germany
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Schleswig-Holstein
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Germany
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Frankfurt
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Germany
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Hamburg
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Calabria
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Rome
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Italy
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Siena
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Podkarpackie
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Bialystok
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Carolina
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Puerto Rico
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San Juan
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Qatar
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Ad Dawhah
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Spain
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Barcelona
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Spain
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Badalona
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Cordoba
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Spain
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Manises
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Spain
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Santa Cruz de Tenerife
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Spain
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Viladecans
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United Kingdom
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Bath
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United Kingdom
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Edinburgh
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United Kingdom
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Londonderry
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United Kingdom
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Manchester
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United Kingdom
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Preston
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
AbbVie
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
An interventional Phase 4 open-label, randomized, controlled, parallel-group, multi-country study in participants with psoriatic arthritis (PsA) consisting of 2 parts: Part 1 (Day 1 up to Week 16) is designed to compare the achievement of minimal disease activity (MDA) between participants randomized to either adalimumab in combination with methotrexate (MTX) or MTX alone escalated to the highest recommended or tolerable dose; Part 2 (Week 16 through Week 32) is designed to evaluate the maintenance or achievement of MDA on 4 different treatment regimens using adalimumab and/or MTX, with participant allocation based on the initial randomized treatment and achievement of MDA in Part 1, and with rescue treatment option.
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Trial website
https://clinicaltrials.gov/study/NCT02814175
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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AbbVie Inc.
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Address
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AbbVie
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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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)
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When will data be available (start and end dates)?
Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
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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 Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
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Available for what types of analyses?
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How or where can data be obtained?
IPD available at link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html
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What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/75/NCT02814175/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/75/NCT02814175/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT02814175