A study of subjects with Psoriatic Arthritis to investigate the effectiveness of adalimumab introduction compared with methotrexate dose escalation

• Register: EUCTR
• Last refreshed on: 20 July 2020
• Main ID: EUCTR2016-000191-21-PL
• Date of registration: 09/11/2016
• Prospective Registration: Yes
• Primary sponsor: AbbVie Deutschland GmbH & Co. KG
• Public title: A study of subjects with Psoriatic Arthritis to investigate the effectiveness of adalimumab introduction compared with methotrexate dose escalation
• 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)
• Date of first enrolment: 09/11/2016
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000191-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 7
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Australia, Brazil, Bulgaria, Canada, Colombia, Czech Republic, European Union, Germany, Poland, Puerto Rico, Qatar, Spain, United Kingdom, United States

Contacts

• Name: EU Clinical Trials Helpdesk
• Affiliation: AbbVie Ltd.

• Name: EU Clinical Trials Helpdesk
• Affiliation: AbbVie Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Adult male or female, = 18 years of age at screening
2. PsA diagnosis established at least 4 weeks prior to the date of the Screening visit and confirmed by C1ASsification of Psoriatic Arthritis (CASPAR) criteria at the Screening visit
3. Not in MDA at the time of screening, defined as not meeting at least 5 of the following 7 criteria:
• Tender joint count (TJC) = 1 out of 68 assessed
• Swollen joint count (SJC) = 1 out of 66 assessed
• 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
• HAQ-DI score = 0.5
• Tender entheseal points = 1 out of 8 assessed
4. Has active arthritis defined as fulfilling both the below criteria at screening and baseline visits:
• = 3 tender joints (out of 68 assessed)
• = 3 swollen joints (out of 66 assessed)
5. Treated with MTX 15 mg ew for PsA defined as:
• Oral or subcutaneous (sc) administration of MTX for at least 4 weeks prior to screening.
• Change of the MTX administration route (oral or sc) is permitted in this time period if the administered dose of MTX 15 mg ew is not changed,
• This is the first course of MTX the subject has been receiving for the treatment of PsA,
• Subject has not received a dosage of MTX higher than 15 mg ew prior to the screening visit,
• Subject could have been receiving MTX doses lower than 15 mg ew before reaching the stable dose of MTX 15 mg ew defined above,
• If the subject had been on MTX 15 mg ew for = 12 weeks, temporary MTX discontinuation or dose decrease below 15 mg ew for up to 4 weeks is allowed.
6. If subject is receiving concomitant oral corticosteroids, prednisone or equivalent must be = 10 mg/day and the dose must be stable for at least 1 week prior to the baseline visit.
7. If subject is receiving nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase (COX) 2 selective inhibitors, paracetamol (up to the maximum recommended dose in the local country label), the dose must be stable for at least 1 week prior to the baseline Visit.
8. If subject is receiving other csDMARDs in addition to MTX (i.e., sulfasalazine), the dose must be stable for at least 4 weeks prior to the baseline visit. If csDMARDs are discontinued before study enrollment, the discontinuation must occur at least 4 weeks prior to the baseline Visit.
• Leflunomide should be discontinued at least 4 weeks prior to the baseline visit.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 228
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

Exclusion criteria:
1. Has contraindication(s) to adalimumab therapy and/or known hypersensitivity to adalimumab or its excipients (refer to SmPC or prescribing information)
2. Has history of MTX intolerance/toxicity
3. Has medical condition(s) precluding MTX dose increase above 15 mg ew
4. Has had prior exposure to any tumor necrosis factor (TNF) inhibitor, other mechanism of action biologic DMARD (bDMARD) or any systemic biologic agent in general



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Psoriatic Arthritis
MedDRA version: 21.0 Level: LLT Classification code 10037160 Term: Psoriatic arthritis System Organ Class: 100000004859

Intervention(s)

Trade Name: Humira 40mg/0.8ml solution for injection in pre-filled syringe
Product Name: Adalimumab
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Adalimumab
CAS Number: 331731-18-1
Current Sponsor code: Humira
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Trade Name: Metoject PEN 15 mg/0.30 ml solution for injection in pre-filled pen
Product Name: Methotrexate
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Methotrexate
CAS Number: 59-05-2
Other descriptive name: METHOTREXATE
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 15-

Trade Name: Metoject PEN 20 mg/0.40 ml solution for injection in pre-filled pen
Product Name: Methotrexate
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Methotrexate
CAS Number: 59-05-2
Other descriptive name: METHOTREXATE
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 20-

Trade Name: Metoject PEN 25 mg/0.50 ml solution for injection in pre-filled pen
Product Name: Methotrexate
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Methotrexate
CAS Number: 59-05-2
Other descriptive name: METHOTREXATE
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 25-

Trade Name: MTX HEXAL 5 mg tablets
Product Name: Methotrexate
Pharmaceutical Form: Tablet
INN or Proposed INN: Methotrexate
CAS Number: 59-05-2
Other descriptive name: METHOTREXATE
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Main Objective: To compare the effectiveness based on the achievement of minimal disease activity (MDA) at Week 16 between subjects who had adalimumab introduced and those that had methotrexate (MTX) escalated to the highest recommended dose of 20–25 mg every week (ew) or highest tolerable dose up to 25 mg ew after inadequate disease control on the initial MTX therapy.

Primary end point(s): The proportion of subjects achieving minimal disease activity (MDA) at Week 16 on adalimumab 40 mg eow plus MTX 15 mg ew as compared with subjects on MTX alone escalated to 20–25 mg or highest tolerable dose ew.

Timepoint(s) of evaluation of this end point: 16 weeks

Secondary Objective: •To compare the effectiveness at Week 16 between subjects who had adalimumab introduced and those that had MTX escalated to the highest recommended dose of 20-25mg ew or highest tolerable up to 25mg ew based on following clinical, functional and quality of life measures:
-Psoriatic Arthritis Disease Activity Score (PASDAS)
-Disease Activity in Psoriatic Arthritis (DAPSA) score
-Psoriatic Arthritis Impact of Disease (PsAID) score
-American College of Rheumatology criteria (ACR)
-Disease Activity Score 28 (DAS28)
-Psoriasis Area and Severity Index (PASI)
-Health Assessment Questionnaire Disability Index (HAQ-DI)
-Short Form Health Survey 36 (SF-36) scores: total, physical component summary (PCS) and mental component summary (MCS)
-Dermatology Life Quality Index (DLQI)
-Leeds Enthesitis Index (LEI)
-Tender dactylitic digit count
•To evaluate the achievement of MDA at Week 32 on each of the four different treatment regimens involving adalimumab and/or MTX in Part 2 of the study

Secondary Outcome(s)

Secondary end point(s): ? The following outcomes after 16 Weeks of treatment with adalimumab 40 mg eow plus MTX 15 mg ew compared with MTX alone escalated to 20-25 mg or highest tolerable dose ew:
- Change in PASDAS from baseline
- Change in DAPSA score from baseline
- Change in PsAID score from baseline
- Proportion of subjects achieving ACR 20/50/70 response
- Change in DAS28-CRP score from baseline
- Proportion of subjects achieving PASI 75/90/100 response among subjects with BSA = 3%
- Change in HAQ-DI score from baseline
- Changes in total SF-36 score, PCS and MCS from baseline
- Change in DLQI score from baseline
- Change in Leeds Enthesitis Index (LEI) from baseline
- Change in tender dactylitic digit count from baseline
? The proportion of subjects in MDA at Week 32 on each of the four different treatment regimens (Arms 1-4) in Part 2 of the study

Timepoint(s) of evaluation of this end point: 16 week or 32 weeks depending on secondary endpoint

Secondary ID(s)

2016-000191-21-BG

M14-496

Source(s) of Monetary Support

AbbVie Inc.

Ethics review

Status: Approved
Approval date: 09/11/2016
Contact: