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

A Phase 4 Open-label Randomized Controlled Study COmparing the Effectiveness of Adalimumab iNTROduction and Methotrexate Dose escaLation in Subjects With Psoriatic Arthritis (CONTROL)

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.

Study Overview

• Status: Completed
• Conditions: Psoriatic Arthritis
• Intervention / Treatment: Drug: methotrexate (MTX); Biological: adalimumab (ADA)

• Study Type: Interventional
• Enrollment (Actual): 246
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital /ID# 153144
    • Kogarah, New South Wales, Australia, 2217
      • Optimus Clinical Research Pty. /ID# 153145
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital /ID# 153147
    • Paramatta, New South Wales, Australia, 2150
      • BJC Health /ID# 153875
  • Victoria
    • Melbourne, Victoria, Australia, 3128
      • Box Hill Hospital /ID# 153146
• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre /ID# 152345
  • Sao Paulo
    • Santo André, Sao Paulo, Brazil, 09060-870
      • Faculdade de Medicina do ABC /ID# 152344
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • MHAT Trimontsium /ID# 152658
  • Sofia, Bulgaria, 1505
    • Diag Consult Ctr 17 Sofia EOOD /ID# 152657
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5M 0H4
      • Rheumatology Research Assoc /ID# 161600
  • British Columbia
    • Victoria, British Columbia, Canada, V8V 3M9
      • Percuro Clinical Research, Ltd /ID# 161601
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1M3
      • Manitoba Clinic /ID# 151939
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1C 5B8
      • St. Clare's Mercy Hospital /ID# 159680
  • Ontario
    • Barrie, Ontario, Canada, L4M 6L2
      • The Waterside Clinic /ID# 151938
    • Hamilton, Ontario, Canada, L8N 1Y2
      • Adachi Medicine Prof. Corp /ID# 152575
  • Quebec
    • Rimouski, Quebec, Canada, G5L 8W1
      • Ctr. de Rheum de l'est du QC /ID# 151937
    • Sainte-foy, Quebec, Canada, G1V 3M7
      • Groupe de Recherche en Maladies Osseuses /ID# 205693
• Colombia
  • Bogota, Colombia, 111121
    • Riesgo de Fractura S.A - CAYRE /ID# 153817
  • Medellin, Colombia, 050034
    • San Vicente Fundacion /Id# 171324
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 110221
      • Centro de Investigacion en Reumatologia y Especialidades Medicas- CIREEM SAS /ID# 151954
• Czechia
  • Jihlava
    • Jihlava 1, Jihlava, Czechia, 586 01
      • Revmatolog s.r.o. /ID# 151753
  • Praha 4
    • Prague 4, Praha 4, Czechia, 140 00
      • Nuselská poliklinika, Revmatologie /ID# 151754
• Germany
  • Frankfurt, Germany, 60590
    • CIRI GmbH /ID# 152228
  • Hamburg, Germany, 22391
    • Hamburger Rheuma I /ID# 164055
  • Baden-Wuerttemberg
    • Heidelberg, Baden-Wuerttemberg, Germany, 69120
      • Universitaetsklinik Heidelberg /ID# 152229
  • Niedersachsen
    • Bruchhausen-Vilsen, Niedersachsen, Germany, 27305
      • Fachpraxis fuer Rheumatologie und Osteologie /ID# 203982
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Univ Hosp Schleswig-Holstein, Campus Kiel, Klinik furer Innere Medizin /ID# 152231
• Italy
  • Rome, Italy, 00161
    • Azienda Ospedaliera Policlinic /ID# 152011
  • Siena, Italy, 53100
    • A.O. Universitaria Senese /ID# 152012
  • Calabria
    • Catanzaro, Calabria, Italy, 88100
      • Universita di Catanzaro Magna Graecia /ID# 152013
• Poland
  • Bialystok, Poland, 15-879
    • ClinicMed Badurski i wspolnicy SJ /ID# 151987
  • Mazowieckie
    • Grodzisk Mazowiecki, Mazowieckie, Poland, 05-825
      • McBk Sc /Id# 163089
    • Warsaw, Mazowieckie, Poland, 01-518
      • Centrum Medyczne AMED /ID# 164047
  • Podkarpackie
    • Stalowa Wola, Podkarpackie, Poland, 37-450
      • SANUS Szpital Specjalistyczny /ID# 151988
• Puerto Rico
  • Carolina, Puerto Rico, 00983
    • Dr. Ramon L. Ortega-Colon, MD /ID# 152957
  • San Juan, Puerto Rico, 00917
    • GCM Medical Group, PSC /ID# 152091
• Qatar
  • Ad Dawhah
    • Doha, Ad Dawhah, Qatar
      • Hamad Hospital /ID# 152334
• Spain
  • Badalona, Spain, 08916
    • Hospital Univ Germans Trias I Pujol /ID# 151760
  • Cordoba, Spain, 14004
    • Hospital Universitario Reina S /ID# 151761
  • Manises, Spain, 46940
    • Hospital Manises /ID# 162778
  • Santa Cruz de Tenerife, Spain, 38320
    • Hospital Univ Canarias /ID# 206489
  • Viladecans, Spain, 8840
    • Hospital de Viladecans /ID# 163875
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Corporac Sanitaria Parc Tauli /ID# 151759
• United Kingdom
  • Bath, United Kingdom, BA1 1RL
    • Royal National Hosp for Rheuma /ID# 152767
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital /ID# 155195
  • Londonderry, United Kingdom, BT47 6SB
    • Altnagelvin Area Hospital /ID# 152766
  • Manchester, United Kingdom, M13 9WL
    • Central Manchester University /ID# 152765
  • Preston, United Kingdom, BT47 3EN
    • Lancashire Care NHS Foundation /ID# 152769
• United States
  • Arizona
    • Sun City, Arizona, United States, 85351
      • AZ Arthritis & Rheum Research /ID# 161796
  • Florida
    • Miami, Florida, United States, 33126
      • LeJenue Research Associates /ID# 200093
  • Illinois
    • Vernon Hills, Illinois, United States, 60061
      • Deerbrook Medical Associates /ID# 158655
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70836-6455
      • Ochsner Clinic Foundation /ID# 155178
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Clinical Pharmacology Study Gr /ID# 161057
  • Michigan
    • Saint Clair Shores, Michigan, United States, 48081
      • Shores Rheumatology, PC /ID# 162697
  • North Carolina
    • New Bern, North Carolina, United States, 28562
      • Coastal Carolina Health Care /ID# 152088
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington LLC /ID# 152089
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Ctr Clinical Res /ID# 152087
  • Texas
    • Dallas, Texas, United States, 75231
      • Metroplex Clinical Research /ID# 162486
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Medical Center /ID# 162051
  • West Virginia
    • South Charleston, West Virginia, United States, 25309
      • West Virginia Research Inst /ID# 157815

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From Day 1 to Week 16
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.	From Day 1 to Week 16
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.	From Day 1 to Week 16
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.	From Day 1 to Week 16
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.	Week 16
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.	From Day 1 to Week 16
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).	Week 32
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. .	From Day 1 to week 16
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.	From Day 1 to Week 16
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.	From Day 1 to Week 16
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.	Week 16
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.	From Day 1 to Week 16

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2016
• Primary Completion (Actual): September 23, 2019
• Study Completion (Actual): March 19, 2020

Study Registration Dates

• First Submitted: June 21, 2016
• First Submitted That Met QC Criteria: June 24, 2016
• First Posted (Estimate): June 27, 2016

Study Record Updates

• Last Update Posted (Actual): November 23, 2020
• Last Update Submitted That Met QC Criteria: October 30, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Psoriatic Arthritis
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Adalimumab; Methotrexate
• Other Study ID Numbers: M14-496; 2016-000191-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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.
• IPD Sharing Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• 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