A Multicenter Study of the Efficacy and Safety of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects with Axial Spondyloarthritis

• Register: EUCTR
• Last refreshed on: 10 March 2014
• Main ID: EUCTR2009-010643-14-CZ
• Date of registration: 25/06/2009
• Prospective Registration: Yes
• Primary sponsor: AbbVie Deutschland GmbH & Co. KG
• Public title: A Multicenter Study of the Efficacy and Safety of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects with Axial Spondyloarthritis
• Scientific title: A Multicenter Study of the Efficacy and Safety of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects with Axial Spondyloarthritis
• Date of first enrolment: 09/09/2009
• Target sample size: 194
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-010643-14
• 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

Countries of recruitment

Czech Republic, France, Germany, Netherlands, Spain, United Kingdom

Contacts

• Name: Abbott House Vanwall Business Park
• Affiliation: AbbVie Ltd.

• Name: Abbott House Vanwall Business Park
• Affiliation: AbbVie Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subject is = 18 years of age;
2. Subject must have had an inadequate response to, or intolerance to at least one NSAID or have a contraindication for NSAIDs as defined by the Investigator;
3. Subject must have chronic back pain (of at least 3 months duration) with onset at age < 45 years;
4. MRI evidence of active inflammatory lesions of sacroiliac joints (past or present) with definite bone marrow edema/osteitis, suggestive of sacroiliitis associated with SpA PLUS = 1 of the clinical criteria listed below:
OR
Positive HLA-B27 PLUS = 2 of the clinical criteria listed below other than HLA-B27 positivity:
? Inflammatory back pain defined as the presence at Screening of at least 4 out of the following 5 parameters: 1) age at onset < 40 yrs, 2) insidious onset, 3) improvement with exercise, 4) no improvement with rest, 5) night pain with improvement upon getting up;
? Arthritis (past or present);
? Heel enthesitis (past or present);
? Anterior Uveitis confirmed by an ophthalmologist (past or present);
? Dactylitis (past or present);
? Crohn's disease or ulcerative colitis (past or present);
? Good prior response to NSAIDs – back pain is not present anymore or much better 24 to 48 hours after a full dose of a NSAID;
? Family history of SpA;
? Positive HLA-B27;
? Elevated CRP.
(See Appendix G of the protocol for definition of SpA features)
5. Subjects must have baseline disease activity as defined by having a Total Back Pain VAS (Appendix E) score =40 mm and BASDAI (Appendix F) = 4 at both the Screening and Baseline visit;
6.If female, subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) or is of childbearing potential and is practicing an approved method of birth control throughout the study and for 150 days after last dose of study drug. The results of the serum pregnancy test performed during the Screening Period and urine pregnancy test performed at the Baseline Visit must be negative.
Examples of approved methods of birth control include the following:
? Condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD);
? Oral, parenteral or intravaginal contraceptives for 90 days prior to study drug administration;
? A vasectomized partner.
7. Subject is judged to be in good health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, chest x-ray (CXR), and a 12-lead electrocardiogram (ECG) performed at Screening;
? Subject has a negative PPD test (or equivalent) and CXR (PA and lateral view) at Screening (Section 5.3.1.1). If the subject had a positive PPD test (or equivalent) and/or CXR (PA and/ or lateral view) consistent with prior TB exposure, the subject must initiate, be currently receiving or have documented completion of a course of anti-TB therapy (Section 5.3.1).
8. Inclusion Criteria deleted in Amendment 1.
9. Subjects must be able and willing to provide written informed consent and comply with the requirements of this study protocol;
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for
Exclusion criteria:
1. Subject fulfilling a diagnosis of ankylosing spondylitis (as defined by the modified New York criteria; at or prior to the Screening Visit;
2. Subject with a past or present diagnosis of psoriasis or psoriatic arthritis;
3. Prior exposure to any biologic therapy with a potential therapeutic impact on SpA, including anti-TNF therapy;
4. Enclusion Criteria deleted in Amendment 1.
5. If entering the study on concomitant Disease-Modyfying Anti-Rheumatic Drugs (DMARDs), subject not on stable dose of MTX (= 25 mg per week) and/or SSZ (= 3 g per day) and/or hydroxychloroquine (= 400 mg per day) for 28 days prior to the Baseline Visit;
6. If entering the study on concomitant oral corticosteroids, subject not on stable dose of prednisone (= 10 mg per/day) (or oral corticosteroid equivalents) and/or NSAIDs for at least 14 days prior to the Baseline Visit;
7. Subject has received cyclosporine or second line anti-rheumatic therapy (except MTX, SSZ, hydroxychloroquine or azathioprine) within 28 days prior to the Baseline Visit;
8. Subject has been treated with intra-articular joint injection(s) or spinal/ paraspinal injections(s) of corticosteroids in the preceding 28 days prior to the Baseline Visit;
9. Subject has been treated with any investigational drug of chemical or biologic nature within a minimum of 30 days or five half lives (whichever is longer) of the drug prior to the Baseline Visit;
10. Infection(s) requiring treatment with intravenous (IV) antibiotics, IV antivirals, or IV antifungals within 30 days prior to the Baseline Visit or oral antibiotics, oral antivirals, or oral antifungals within 14 days prior to the Baseline Visit;
11. Subject with extra-articular manifestations (e.g., inflammatory bowel disease, uveitis, etc.) that is not clinically stable for at least 30 days prior to study entry;
12. Subject has a history of inflammatory arthritis of a different etiology other than axial spondyloarthritis (e.g., rheumatoid arthritis, gout, systemic lupus erythematosus, polyarticular or systemic juvenile idiopathic arthritis);
13. Known hypersensitivity to the excipients of adalimumab as stated in the label;
14. History of CNS demyelinating disease or neurologic symptoms suggestive of CNS demyelinating disease;
15. History of listeriosis, histoplasmosis, chronic or active Hepatitis B infection, human immunodeficiency virus (HIV) infection, immunodeficiency syndrome, chronic recurring infections or active TB;
16. History of moderate to severe congestive heart failure (NYHA class III or IV), recent cerebrovascular accident and any other condition which, in the opinion of the Investigator, would put the subject at risk by participation in the protocol;
17. Evidence of dysplasia or history of malignancy (including lymphoma and leukemia) other than a successfully treated non-metastatic cutaneous squamous cell, basal cell carcinoma or localized carcinoma in situ of the cervix;
18. Female subjects who are pregnant or breast-feeding or considering becoming pregnant during the study;
19. History of clinically significant drug or alcohol abuse in the last 12 months;
20. Clinically significant abnormal screening laboratory results as evaluated by the Investigator
21. Subject is considered by the Investigator, for any reason, to be an unsuitable candidate for the study.
22. If entering the study on concomitant azathioprine, subject not on stable dose (= 150 mg/day) for 28 days prior to the Baseline Visit or on azathioprine a

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

Health Condition(s) or Problem(s) studied

Active axial spondyloarthritis
MedDRA version: 15.1 Level: PT Classification code 10051265 Term: Spondyloarthropathy System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Trade Name: Humira 40 mg solution for injection in pre-filled syringe
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Adalimumab
CAS Number: 331731-18-1
Other descriptive name: ABT-Humira
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: The objective of this study is to evaluate the efficacy and safety of adalimumab 40 mg given every other week (eow) subcutaneously (SC) compared to placebo for 12 weeks followed by open-label safety and efficacy assessments in subjects with active axial spondyloarthritis not fulfilling the modified New York criteria for AS who have had an inadequate response to, or intolerance to one or more NSAIDs or have a cotraindication for NSAIDs.

Primary end point(s): The primary efficacy variable is the proportion of subjects who have achieved ASAS40 response at the Week 12 Visit.

Secondary Objective: N/A

Secondary ID(s)

M10-791

2009-010643-14-FR

Source(s) of Monetary Support

AbbVie Inc.