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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 11 December 2017
Main ID:  EUCTR2013-004604-19-DE
Date of registration: 03/06/2014
Prospective Registration: Yes
Primary sponsor: Heinrich-Heine-Universität Düsseldorf
Public title: Effect of Adalimumab plus Methortrexat (MTX) versus Placebo plus MTX on cartilage in early RA patients
Scientific title: Delayed Gadolinium-enhanced Magnetic resonance Imaging (MRI) of Cartilage - A pilot study to measure the effect of Adalimumab plus Methotrexat (MTX) versus Placebo plus MTX on cartilage in early rheumatoid arthritis (RA) patients
Date of first enrolment: 06/08/2014
Target sample size: 30
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004604-19
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2  
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no
Countries of recruitment
Germany
Contacts
Name: Koordinierungszentrum kl. Studien   
Address:  Moorenstrasse 5 40225 Duesseldorf Germany
Telephone: 4902118119701
Email: dorothea.schilken@med.uni-duesseldorf.de
Affiliation:  Universiätsklinikum Düsseldorf
Name: Koordinierungszentrum kl. Studien   
Address:  Moorenstrasse 5 40225 Duesseldorf Germany
Telephone: 4902118119701
Email: dorothea.schilken@med.uni-duesseldorf.de
Affiliation:  Universiätsklinikum Düsseldorf
Key inclusion & exclusion criteria
Inclusion criteria:
1. Subject is = 18 years of age.
2. Subject has a diagnosis of early RA (ERA) fulfilling the 2010 ACR criteria for classification of RA) and has disease duration less than 12 months from symptoms onset.
3. MCP II and/or MCP III arthritis at the clinically dominant – selected for MRI- hand indicated by joint tenderness.
4. DAS28 > 3.2.
5. Anti-citrullinated peptide antibodies (ACPA) and/or RF positive.
6. Discrete low-grade erosions (Sharp van der Heijde (SHS) Score 0-2) but no larger erosions at MCP II/III joints of the clinically dominant hand are allowed.
7. Therapy-naive for disease modifying drugs (DMARD).
8. Oral Prednisone or prednisone equivalent at = 10 mg/day is allowed during the study and should be kept at a stable dose. The dose must not be changed at least 4 weeks prior to the baseline visit and at least 6 weeks prior to the Week 24 visit. One prednisone pulse not exceeding the duration of 14 days for acute medical conditions other than RA with an indication for steroid pulse treatment is allowed. The prednisone pulse is not permitted within 6 weeks prior to the Week 24.
9. Subject is judged to be in good general health as determined by the Coordinating Investigator based upon the results of medical history, laboratory profile, physical examination, chest X-ray (CXR), and 12-lead electrocardiogram (ECG) performed at Screening.
10. Subjects must be able and willing to self-administer SC injections or have a qualified person available to administer SC injections.

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 27
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion criteria:
1. Subject has previous exposure to any systemic biologic therapy (e.g. abatacept, tocilizumab) including anti-TNF therapy (e.g., infliximab, golimumab, certolizumab pegol, etanercept) including adalimumab.
2. Subject has been previously treated with DMARDs or MTX.
3. Joint injections into the reference joint (MCP II) are not allowed. Two joint injections of corticosteroids, not exceeding the equivalent of 40 mg prednisone
in other joints are allowed. Joint injections are not permitted 6 weeks prior to the Week 24 assessment. Two joints may be injected at the same visit and will be counted as two injections. For the analysis of the Tender joint count (TJC) and Swollen joint count (SJC) these joints will be considered "not assessable" for three months from the time of the intra-articular injection.
4. Subject has undergone joint surgery within the preceding two months (at joints to be assessed within the study).
5. Subject has a history of acute inflammatory joint disease of different origin other than RA (e.g., mixed connective tissue disease, seronegative spondyloarthropathy, psoriatic arthritis, Reiter's syndrome, fibromyalgia, systemic lupus erythematosus or any arthritis with onset prior to age 17 years)
6. Subject has been treated with any investigational drug of a "chemical" nature within two months prior to study entry (screening visit).
7. Subject has a poorly controlled medical condition, such as uncontrolled diabetes, unstable heart disease, congestive heart failure, recent cerebrovascular accidents and any other condition which, in the opinion of the Investigator, would put the subject at risk by participation in the study.
8. Subject has a history of clinically significant hematologic (e.g., severe anemia, leukopenia, thrombocytopenia), renal, liver disease (e.g., fibrosis, cirrhosis, hepatitis B and C), or gastroenteric ulcer.
9. Subject has a history or a present renal dysfunction (GFR < 30 ml/min/1.73m2) [Kaewlai R et al. 2012].
10. Subject has history of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease and/or diagnosis of central demyelinating disease.
11. Subject has history of cancer or lymphoproliferative disease other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix.
12. Subject has a history of listeriosis, histoplasmosis, untreated TB, persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous (IV) anti-infectives within 30 days or oral anti-infectives within 14 days prior to the Baseline visit.
13. Subject currently uses or plans to use anti-retroviral therapy at any time during the study.
14. Subject is known to have immune deficiency, history of HIV or is immunocompromised.
15. Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study or for 150 days after the last dose of study medication.
16. Subject has a history of clinically significant drug or alcohol usage in the last year or cannot maintain an alcohol intake of 30 g a day or less throughout the study.
17. Subject has a positive Tb Screening test.
18. Subject with evidence of earlier or present hepatitis B or C infection.
19. Subjects with a pacemaker, defibrillator, or cerebral aneurysm clip or planning to receive any such device within the duration of the study
20. Subjects with a previous history of kidney failure, dialysis, or


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
patients with early progressive rheumatoid arthritis
MedDRA version: 17.0 Level: LLT Classification code 10066578 Term: Progression of rheumatoid arthritis System Organ Class: 100000004859
Therapeutic area: Body processes [G] - Bones and nerves physological processes [G11]
Intervention(s)

Trade Name: Humira 40mg Injektionslösung
Product Name: Humira
Pharmaceutical Form: Injection
Pharmaceutical form of the placebo: Injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)
Main Objective: To compare longitudinally the effect of adalimumab plus methotrexate (MTX) versus MTX monotherapy on cartilage Glycosaminglycan (GAG) content, reflected by delayed Gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) index, in patients with early progressive rheumatoid arthritis (RA), who had not previously received any disease modifying antirheumatic drug (DMARD) or biolologic treatment.
Primary end point(s): Mean Intergroup difference of pooled (per patient) dGEMRIC index (T1 [ms]) of the MCP II and MCP III joints of the clinically dominant hand, measured by variable flip-angle imaging 3T MRI at week 24 versus baseline.
Secondary Objective: • To assess differences in cartilage thickness between patients initially treated with adalimumab plus MTX versus MTX monotherapy as measured by 3T (threetime) MRI at weeks 12 and 24 and correlate changes from baseline to week 24 in each treatment arm with changes in dGEMRIC index.
• To assess differences of specific bio-respectively serum cartilage markers (e.g. C2c, Collagen Typ II, COMP, MMP-3, YKL-40) in patients initially treated with adalimumab plus MTX versus MTX monotherapy at week 0, 12 and 24 and to correlate changes in serum cartilage markers (e.g. C2c, Collagen Type II, COMP, MMP-3, YKL-40) from baseline in each treatment arm with changes in dGEMRIC index from baseline to week 24.
• To compare clinical and functional outcome (American college of rheumatology (ACR) response, Disease-activity-score (DAS)28, (HAQ)) between treatment groups at week 12 and 24 and assess changes of these parameters from baseline up to weeks 12 and 24 in each treatment group.

Timepoint(s) of evaluation of this end point: after 24 weeks (End of Study)
Secondary Outcome(s)
Secondary end point(s): •Proportion of patients showing no decrease in dGEMRIC index from week 0 to week 24 in each treatment group
•Proportion of patients in each treatment group showing an increase of dGEMRIC index from week 0 to weeks 12 and 24
•Difference of cartilage thickness / Joint space narrowing (JSN) at MCP II and MCP III joints of the clinically dominant hand from baseline to weeks 12 and 24 in each treatment group, determined by 3T MRI using T1 weighed gradient echo images
•Total rheumatoid arthritis magnetic resonance Imaging (RAMRI) score and subscores for synovitis, osteitis and bone erosions at MCP II/III joints of the clinically dominant hand in each treatment group at 0, 12 and 24 weeks and intergroup difference of changes from week 0 to weeks 12 and 24
•Proportion of subjects showing no decrease of cartilage thickness / JSN in 3T MRI at week 24 compared to baseline
•Proportion of subjects with improvement in RAMRI score for synovitis, osteitis and bone erosion in each treatment group at week 24 compared to baseline
•Proportion of subjects with decrease in rate of early enhancement in perfusion MRI in each treatment group
•Mean and median concentration of cartilage markers (e.g. Collagen Typ II, COMP, MMP-3, YKL-40) at week 0, 12 and 24 and changes from baseline to week 12 and 24 in each treatment arm
•Proportion of subjects in each treatment group who are in clinical remission (DAS 28 < 2.6) or low disease activity (DAS 28 >2.6 <3.2) at 12 and 24 weeks
•Mean and median DAS28 at 0, 12 and 24 weeks and changes in DAS28 from baseline to week 12 and 24 in each treatment arm
•ACR 20, 50 and 70 response at 12 and 24 weeks in each treatment arm
•Mean and median total health assessment question (HAQ) at 0, 12 and 24 weeks and changes in total HAQ from baseline to week 12 and 24 in each treatment group
Timepoint(s) of evaluation of this end point: after 24 weeks (End of Study)
Secondary ID(s)
CAR-ERA
Source(s) of Monetary Support
AbbVie Deutschland GmbH&Co.KG
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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