Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Subjects With Psoriatic Arthritis to Investigate the Effectiveness of Adalimumab Introduction Compared With Methotrexate Dose Escalation (CONTROL) (CONTROL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02814175
Recruitment Status : Completed
First Posted : June 27, 2016
Results First Posted : November 23, 2020
Last Update Posted : November 23, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie

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.

Condition or disease Intervention/treatment Phase
Psoriatic Arthritis Drug: methotrexate (MTX) Biological: adalimumab (ADA) Phase 4

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 246 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : August 5, 2016
Actual Primary Completion Date : September 23, 2019
Actual Study Completion Date : March 19, 2020


Arm Intervention/treatment
Active Comparator: Part 1: MTX Escalated Dose
Methotrexate (MTX) escalated to 20 - 25 mg or highest tolerable dose every week (ew)
Drug: methotrexate (MTX)
Experimental: Part 1: ADA + MTX
Adalimumab (ADA) 40 mg every other week (eow) in combination with MTX 15 mg ew
Drug: methotrexate (MTX)
Biological: adalimumab (ADA)
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
Drug: methotrexate (MTX)
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
Drug: methotrexate (MTX)
Biological: adalimumab (ADA)
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
Biological: adalimumab (ADA)
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
Drug: methotrexate (MTX)
Biological: adalimumab (ADA)



Primary Outcome Measures :
  1. Percentage of Participants Achieving Minimal Disease Activity (MDA) (Non-responder Imputation [NRI]) (Part 1) [ Time Frame: Week 16 ]
    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).


Secondary Outcome Measures :
  1. Change in Dermatology Life Quality Index (DLQI) Score From Baseline (Part 1) [ Time Frame: From Day 1 to Week 16 ]
    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.

  2. Change in Tender Dactylitic Digit Count From Baseline for Participants With Presence of Dactylitis at Baseline (Part 1) [ Time Frame: From Day 1 to Week 16 ]
    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.

  3. Change in Disease Activity Score 28 (DAS28)-C-reactive Protein (CRP) Score From Baseline (Part 1) [ Time Frame: From Day 1 to Week 16 ]
    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.

  4. Change in Psoriatic Arthritis Impact of Disease Score (PsAID) Score From Baseline (Part 1) [ Time Frame: From Day 1 to Week 16 ]
    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.

  5. Percentage of Participants Achieving American College of Rheumatology (ACR) 20/50/70 Response (Part 1) [ Time Frame: Week 16 ]
    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.

  6. Change in Leeds Enthesitis Index (LEI) From Baseline (Part 1) for Participants With Presence of LEI at Baseline [ Time Frame: From Day 1 to Week 16 ]
    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.

  7. Percentage of Participants in MDA in Part 2 of the Study (Week 32) [ Time Frame: 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).

  8. Change in Psoriatic Arthritis Disease Activity Score (PASDAS) From Baseline (Part 1) [ Time Frame: From Day 1 to week 16 ]

    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.

    .


  9. Change in Short Form Health Survey 36 (SF-36) Score From Baseline (Part 1) [ Time Frame: From Day 1 to Week 16 ]
    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.

  10. Change in HAQ-DI Score From Baseline (Part 1) [ Time Frame: From Day 1 to Week 16 ]
    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.

  11. 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) [ Time Frame: Week 16 ]
    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.

  12. Change in Disease Activity in Psoriatic Arthritis Score (DAPSA) Score From Baseline (Part 1) [ Time Frame: From Day 1 to Week 16 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02814175


Locations
Show Show 60 study locations
Sponsors and Collaborators
AbbVie
Investigators
Layout table for investigator information
Study Director: AbbVie Inc. AbbVie
  Study Documents (Full-Text)

Documents provided by AbbVie:
Study Protocol  [PDF] June 3, 2019
Statistical Analysis Plan  [PDF] June 10, 2019

Layout table for additonal information
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02814175    
Other Study ID Numbers: M14-496
2016-000191-21 ( EudraCT Number )
First Posted: June 27, 2016    Key Record Dates
Results First Posted: November 23, 2020
Last Update Posted: November 23, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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 Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Access Criteria: 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.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AbbVie:
Psoriatic Arthritis
Additional relevant MeSH terms:
Layout table for MeSH terms
Arthritis
Arthritis, Psoriatic
Joint Diseases
Musculoskeletal Diseases
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Adalimumab
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents