The aim of the study is to assess the efficacy and safety of treatment with adalimumab in patients with peripheral spondyloarthritis (without AS of PsA). Furthermore, the effect of adalimumab will be investigated on systemic and local disease…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy: Patient*s Global Assessment of Disease at week 12
Safety: detailled questionaire for adverse events, clinical examination,
laboratory evaluation (hematology, chemistry, urine analysis)
Secondary outcome
Efficacy: Patient's Global Assessment of Disease at week 24, Physician*s Global
Assessment of Disease, BASDAI, number of swollen and tender joints, CRP and ESR
Serum biomarkers: MMP3, MRP8/14, cartilage and bone biomarkers, autoantibodies
Synovial biomarkers: celinfiltration, cytokine expression, MMP expression,
vascularisation
Function and quality of life: Health Assessment Questionnaire; AMC Linear
Disability Score; HUI-3
Background summary
Spondyloarthritis is a frequent form of chronic, inflammatory arthritis and is
divided in different subtypes: ankylosing spondylitis (AS), psoriatic arthritis
(PsA), reactive arthritis, arthritis with inflammatory bowel diseases and
undifferentiated spondyloarthritis. Both clinical and pathophysiological data
show that the different subtypes belong to one concept. Almost all
therapeutical trials with TNFalpha blockers are conducted in patients with AS
or PsA. Peripheral spondyloarthritis without AS or PsA counts for almost 20 %
of all patients with spondyloarthritis. This important group has no entrance
tot treatment with TNFalpha blockers, whereas the standard treatment (local
injections with corticosteroids, NSAID of sulphasalazine) is not efficient
enough in 25-50% of the patients. Furthermore, there are now (preliminary) data
that TNFalpha blockers are effective in this patient group.
Study objective
The aim of the study is to assess the efficacy and safety of treatment with
adalimumab in patients with peripheral spondyloarthritis (without AS of PsA).
Furthermore, the effect of adalimumab will be investigated on systemic and
local disease activity (serum and synovial biomarkers), function and quality of
life.
Study design
After screening, patients with active peripheral spondyloarthritis (without AS
of PsA) will be enrolled in a 12-week, randomised, double-blind,
placebo-controlled trial, followed by a 12-week open label extension trial.
Study medication = adalimumab (Humira); dosage = 40 mg every 2 weeks,
subcutaneous injection. The study is conducted in the department of Clinical
Immunology and Rheumatology, AMC, Amsterdam. In total, there are 6 visits:
screening, baseline, and week 6, 12, 18 and 24. At every visit, there is a
clinical evaluation of the disease activity and safety (according the
guidelines of *Good Clinical Practise*) and a laboratory evaluation. If a large
peripheral joint is affected, the patient undergoes a needle-arthroscopy at
baseline, week 12 and week 24, in order to obtain synovial tissue.
Intervention
Therapeutical intervention:
The first 12 weeks the patients are treated with adalimumab (40 mg every 2
weeks, subcutaneous injection) or placebo. The last 12 weeks all patients are
treated with adalimumab (40 mg every 2 weeks, subcutaneous injection).
Procedure:
Venous blood punction at every study visit (40 ml per visit, in total 240 ml)
Arthroscopy at baseline, week 12 and week 24
Study burden and risks
Adalimumab is used worldwide in thousands of patients with chronic arthritis
(rheumatoid arthritis, AS, PsA) and is extensively investigated in clinical
trials. The most reported adverse events are: local skin reaction on the site
of the injection, infections of the upper airways, headache and nausea. Some of
the rare adverse events are: opportunistic infections and reactivation of
tuberculosis, neurological disorders caused by demyelinisation, and allergic
reactions. During treatment with adalimumab, the patient should not receive
vaccinations with living viruses. On the moment, there are not sufficient data
on the effect of adalimumab on the foetus. The therapy can be harmful. Pregnant
women or during lactation are therefore not allowed to participate in the
study.
Beside the risks related to the treatment with adalimumab, there are also risks
related to the procedures. The venous blood punction (40 ml blood at each
visit) and the arthroscopy can cause a vagal reaction. This adverse event is
rarely seen. At the arthroscopy, there is a very small risk (< 0,3%) on a
complication, such as an infection of the joint. Careful disinfection of the
skin and the use of sterile gloves diminish that risk. Reactions on the local
anaesthesia (nausea, nervositas, skin reactions) are rarely seen and disappear
quickly.
In general, the therapeutic effects of treatment with adalimumab are superior
to the extent of the burden and risks associated with participation in the
trial.
Meibergdreef 9 F4-218
1105 AZ Amsterdam ZO
Nederland
Meibergdreef 9 F4-218
1105 AZ Amsterdam ZO
Nederland
Listed location countries
Age
Inclusion criteria
1. Prior to any study procedure, voluntary written informed consent must be obtained, after the nature and purpose of this study are explained
2. Patients should be between 18 and 70 years of age
3. Patients must have a diagnosis of peripheral spondyloarthritis not fulfilling the classification criteria for ankylosing spondylitis or psoriatic arthritis for at least 3 months. The disease must be moderate to severely active as defined by at least 1 swollen and at least 1 tender or painful joints
4. If female, patient should either be of not-childbearing potential (i.e. postmenopausal or surgically sterile) or practice a reliable method of birth control until 150 days post-study (e.g. use of condom, IUD, oral contraceptives) or have a vasectomized partner
5. Patients should have inadequate response to NSAID therapy (non-steroidal, anti-inflammatory drugs)
6. The use of concomitant NSAIDs and corticosteroids is allowed. The dose of corticosteroids should not exceed a prednisone equivalent * 10 mg/day and must be stable for at least 4 weeks prior to baseline
7. The use of concomitant DMARDs (disease modifying anti-rheumatic drugs, Methotrexaat or Sulphasalazine) is allowed. If using DMARDs, patients must have received a minimum of 3 months of therapy and be on a stable dose for at least 4 weeks prior to baseline
8. Patients are considered to be in generally good health based upon the result of a medical history, physical examination, laboratory profile, chest X-ray and ECG
Exclusion criteria
1. Patient has previously received anti-TNF therapy or another investigational drug in the past 2 months
2. Patient has received an intra-articular injection with corticosteroids within 4 weeks prior to baseline
3. Patient has an active articular disease (other than peripheral spondyloarthritis not fulfilling the classification criteria for ankylosing spondylitis or psoriatic arthritis) that could interfere with the assessment of arthritis
4. Patient has a history of active tuberculosis. A PPD test and chest X-ray done at screening should be negative (in case of latent tuberculosis, a patient may enter the study if prophylaxis with isoniazide is begun prior to administration of adalimumab)
5. Patients has a recent history of (or persistent) infection requiring hospitalization or antibiotic treatment within 4 weeks of baseline
6. Patient has a significant history of cardiac, renal, neurological, metabolic or any other disease that may affect his/her participation in this study
7. Patient has a history of malignancy (other than basal cell carcinoma of the skin) in the past 10 years
8. If female, patient should not be pregnant or breast-feeding. A serum pregnancy-test will be performed at screening has to be negative
9. Patient is, in the opinion of the investigator, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-006885-27-NL |
| CCMO | NL25563.018.08 |