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

Psoriatic Arthritis Clinical Trial

— CONTROL  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02814175
• Other study ID #: M14-496
• Secondary ID: 2016-000191-21
• Status: Completed
• Phase: Phase 4
• Start date: August 5, 2016
• Est. completion date: March 19, 2020

Study information

• Verified date: October 2020
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 246
• Est. completion date: March 19, 2020
• Est. primary completion date: September 23, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis

Intervention

Drug:
• methotrexate (MTX)

Biological:
• adalimumab (ADA)

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Bulgaria,  Canada,  Colombia,  Czechia,  Germany,  Italy,  Poland,  Puerto Rico,  Qatar,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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