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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02814175




Registration number
NCT02814175
Ethics application status
Date submitted
21/06/2016
Date registered
27/06/2016
Date last updated
23/11/2020

Titles & IDs
Public title
A Study of Subjects With Psoriatic Arthritis to Investigate the Effectiveness of Adalimumab Introduction Compared With Methotrexate Dose Escalation (CONTROL)
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)
Secondary ID [1] 0 0
2016-000191-21
Secondary ID [2] 0 0
M14-496
Universal Trial Number (UTN)
Trial acronym
CONTROL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Psoriatic Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - methotrexate (MTX)
Other interventions - adalimumab (ADA)

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Part 2: ADA - Participants achieving MDA at Week 16 on ADA 40 mg eow plus MTX 15 mg ew, had MTX completely withdrawn at Week 16 and continued receiving ADA as monotherapy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


Treatment: Drugs: methotrexate (MTX)


Other interventions: adalimumab (ADA)


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
Percentage of Participants Achieving Minimal Disease Activity (MDA) (Non-responder Imputation [NRI]) (Part 1) - 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).
Timepoint [1] 0 0
Week 16
Secondary outcome [1] 0 0
Change in Dermatology Life Quality Index (DLQI) Score From Baseline (Part 1) - 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.
Timepoint [1] 0 0
From Day 1 to Week 16
Secondary outcome [2] 0 0
Change in Tender Dactylitic Digit Count From Baseline for Participants With Presence of Dactylitis at Baseline (Part 1) - 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.
Timepoint [2] 0 0
From Day 1 to Week 16
Secondary outcome [3] 0 0
Change in Disease Activity Score 28 (DAS28)-C-reactive Protein (CRP) Score From Baseline (Part 1) - 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.
Timepoint [3] 0 0
From Day 1 to Week 16
Secondary outcome [4] 0 0
Change in Psoriatic Arthritis Impact of Disease Score (PsAID) Score From Baseline (Part 1) - 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.
Timepoint [4] 0 0
From Day 1 to Week 16
Secondary outcome [5] 0 0
Percentage of Participants Achieving American College of Rheumatology (ACR) 20/50/70 Response (Part 1) - 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.
Timepoint [5] 0 0
Week 16
Secondary outcome [6] 0 0
Change in Leeds Enthesitis Index (LEI) From Baseline (Part 1) for Participants With Presence of LEI at Baseline - 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.
Timepoint [6] 0 0
From Day 1 to Week 16
Secondary outcome [7] 0 0
Percentage of Participants in MDA in Part 2 of the Study (Week 32) - 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).
Timepoint [7] 0 0
Week 32
Secondary outcome [8] 0 0
Change in Psoriatic Arthritis Disease Activity Score (PASDAS) From Baseline (Part 1) - 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.
.
Timepoint [8] 0 0
From Day 1 to week 16
Secondary outcome [9] 0 0
Change in Short Form Health Survey 36 (SF-36) Score From Baseline (Part 1) - 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.
Timepoint [9] 0 0
From Day 1 to Week 16
Secondary outcome [10] 0 0
Change in HAQ-DI Score From Baseline (Part 1) - 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.
Timepoint [10] 0 0
From Day 1 to Week 16
Secondary outcome [11] 0 0
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) - 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.
Timepoint [11] 0 0
Week 16
Secondary outcome [12] 0 0
Change in Disease Activity in Psoriatic Arthritis Score (DAPSA) Score From Baseline (Part 1) - 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.
Timepoint [12] 0 0
From Day 1 to Week 16

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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
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

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
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,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital /ID# 153144 - Camperdown
Recruitment hospital [2] 0 0
Optimus Clinical Research Pty. /ID# 153145 - Kogarah
Recruitment hospital [3] 0 0
Liverpool Hospital /ID# 153147 - Liverpool
Recruitment hospital [4] 0 0
BJC Health /ID# 153875 - Paramatta
Recruitment hospital [5] 0 0
Box Hill Hospital /ID# 153146 - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2170 - Liverpool
Recruitment postcode(s) [4] 0 0
2150 - Paramatta
Recruitment postcode(s) [5] 0 0
3128 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
United States of America
State/province [11] 0 0
West Virginia
Country [12] 0 0
Brazil
State/province [12] 0 0
Rio Grande Do Sul
Country [13] 0 0
Brazil
State/province [13] 0 0
Sao Paulo
Country [14] 0 0
Bulgaria
State/province [14] 0 0
Plovdiv
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Sofia
Country [16] 0 0
Canada
State/province [16] 0 0
Alberta
Country [17] 0 0
Canada
State/province [17] 0 0
British Columbia
Country [18] 0 0
Canada
State/province [18] 0 0
Manitoba
Country [19] 0 0
Canada
State/province [19] 0 0
Newfoundland and Labrador
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
Canada
State/province [21] 0 0
Quebec
Country [22] 0 0
Colombia
State/province [22] 0 0
Cundinamarca
Country [23] 0 0
Colombia
State/province [23] 0 0
Bogota
Country [24] 0 0
Colombia
State/province [24] 0 0
Medellin
Country [25] 0 0
Czechia
State/province [25] 0 0
Jihlava
Country [26] 0 0
Czechia
State/province [26] 0 0
Praha 4
Country [27] 0 0
Germany
State/province [27] 0 0
Baden-Wuerttemberg
Country [28] 0 0
Germany
State/province [28] 0 0
Niedersachsen
Country [29] 0 0
Germany
State/province [29] 0 0
Schleswig-Holstein
Country [30] 0 0
Germany
State/province [30] 0 0
Frankfurt
Country [31] 0 0
Germany
State/province [31] 0 0
Hamburg
Country [32] 0 0
Italy
State/province [32] 0 0
Calabria
Country [33] 0 0
Italy
State/province [33] 0 0
Rome
Country [34] 0 0
Italy
State/province [34] 0 0
Siena
Country [35] 0 0
Poland
State/province [35] 0 0
Mazowieckie
Country [36] 0 0
Poland
State/province [36] 0 0
Podkarpackie
Country [37] 0 0
Poland
State/province [37] 0 0
Bialystok
Country [38] 0 0
Puerto Rico
State/province [38] 0 0
Carolina
Country [39] 0 0
Puerto Rico
State/province [39] 0 0
San Juan
Country [40] 0 0
Qatar
State/province [40] 0 0
Ad Dawhah
Country [41] 0 0
Spain
State/province [41] 0 0
Barcelona
Country [42] 0 0
Spain
State/province [42] 0 0
Badalona
Country [43] 0 0
Spain
State/province [43] 0 0
Cordoba
Country [44] 0 0
Spain
State/province [44] 0 0
Manises
Country [45] 0 0
Spain
State/province [45] 0 0
Santa Cruz de Tenerife
Country [46] 0 0
Spain
State/province [46] 0 0
Viladecans
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Bath
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Edinburgh
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Londonderry
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Manchester
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Preston

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

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/show/NCT02814175
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

Summary results
Other publications