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: 31 July 2012
• Main ID: EUCTR2009-010643-14-GB
• Date of registration: 18/06/2009
• Prospective Registration: Yes
• Primary sponsor: Abbott 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: 13/10/2009
• 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

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;
3. Subject must have chronic back pain (of at least 3 months duration) with onset at age < 45 years;
4. Active inflammatory lesions of sacroiliac joints 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 presence 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.
5. Subjects must have baseline disease activity as defined by having a Total Back Pain VAS score greater than or equal to 40 mm and BASDAI = 4;
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;
8. Subject has a negative PPD test (or equivalent) and CXR (PA and lateral view) at Screening. 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 have had one of the following:
? Prophylactic treatment is initiated prior to administration of study drug; however the course of prophylaxis need not be completed prior to the onset of study drug. Prophylactic treatment will be according to the United States Centers for Disease Control (CDC) recommended preventive therapy for TB or per local guidelines as approved by the Abbott Medical Monitor. Prophylactic treatment should be captured on the concomitant medications page in the CRF and in the source documents. See for Centers for Disease Control (CDC) recommended preventive therapy for TB.
OR
? Subject has documented prophylactic treatment for TB in the past and does not need to repeat this treatment or TB prophylaxis is ongoing;
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-
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 diagnosed with psoriasis;
3. Prior exposure to any biologic therapy including anti-TNF therapy;
4. Subject has received any live (attenuated) vaccines within 52 weeks prior to the Baseline Visit;
5. 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 4 weeks prior to the Baseline Visit;
6. Subject not on stable dose of prednisone (= 10 mg per/day) (or oral corticosteroid equivalents) and/or NSAIDs for at least 2 weeks prior to the Baseline Visit;
7. Subject has received cyclosporine, azathioprine or other second line anti-rheumatic therapy (except MTX, SSZ or hydroxychloroquine) within 4 weeks prior to the Baseline Visit;
8. Subject has been treated with intra-articular joint injection(s) of corticosteroids in the preceding 4 weeks 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 4 weeks prior to study entry;
12. Subject has a history of acute inflammatory arthritis of a different etiology other than axial spondyloarthritis (e.g., rheumatoid arthritis, Reiter's syndrome, systemic lupus erythematosus, or any arthritis with onset prior to age 17 years);
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. Screening clinical laboratory analysis show any of the following abnormal laboratory results:
? Aspartate transaminase (AST) or alanine transaminase (ALT) > 1.5 × the upper limit of normal (ULN)
? Serum total bilirubin = 1.5 mg/dL (= 26 µmol/L); or
? Creatinine > 1.5 mg/dL (133 µmol/L) in subjects < 65 years old and > upper limit of normal range in subjects = 65
21. Subject is considered by the Investigator, for any reason, to be an unsuitable candidate for the study.


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

Health Condition(s) or Problem(s) studied

Active axial spondyloarthritis
MedDRA version: 9.1 Level: LLT Classification code 10051265 Term: Spondyloarthropathy

Intervention(s)

Trade Name: Humira 40 mg solution for injection in pre-filled syringe
Product Name: Humira
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.

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)

2009-010643-14-FR

M10-791