The primary objective is to study changes in synovial inflammation in serial biopsy samples following the administration of tocilizumab in patients with active RA.The secondary objectives of this study are to:I. Assess clinical response at week 16;…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the change in CD68+ macrophages in the synovium between
baseline and week 2 after treatment with tocilizumab.
Secondary outcome
The clinical severity of the affected joints during treatment will be evaluated
at each visit using the following parameters:
* Tender joint count (28 joints)
* Swollen joint count (28 joints)
* Patient*s visual analogue scale (VAS) of global disease activity
* Patient*s VAS of pain
* CRP
* Erythrocyte sedimentation rate (ESR).
Background summary
Tocilizumab is a relatively new therapeutic. The molecular mechanisms of
tocilizumab treatment at te site of inflammation have not yet been studied. The
results from this stud will provide insight into the cellular and molecular
changes after specific IL-6 recpeotr blockkade on different levels.
Study objective
The primary objective is to study changes in synovial inflammation in serial
biopsy samples following the administration of tocilizumab in patients with
active RA.
The secondary objectives of this study are to:
I. Assess clinical response at week 16;
II. Identify synovial biomarkers predictive of the clinical response to
tocilizumab treatment.
Study design
Following a screening period of 4 weeks, active RA patients, who are eligible
to receive tocilizumab treatment in routine rheumatology practice, will be
enrolled in a prospective, open-label study for a period of 16 weeks. Synovial
biopsies from an actively inflamed joint (knee, ankle or wrist) will be
obtained by mini-arthroscopy or ultrasound-guided biopsy before administration
of tocilizumab at baseline, after 2 and 6 weeks of treatment. The serial
biopsies are obtained from the same joint. The baseline visit and first
arthroscopy must be within 3 days before the first administration of
tocilizumab.
Clinical evaluation of joint pain and swelling will be performed at baseline
and repeated after 2, 4, 6, 8, 12, and 16 weeks of treatment. Patients will be
seen for efficacy and safety assessments in accordance with standard guidelines
for clinical practice.
In total there will be nine study visits: screening, week 0 (i.e., baseline),
week 2, week 4, week 6, week 8, week 12, week 16, and week 20 (i.e.,
follow-up). For week 4 and on, there will be a ±3-day deviation for all return
visits. All visits will be fixed with reference to the baseline visit.
Study burden and risks
the risk associated with participation are connected with drawing extra blood,
saliva and the arthroscopy. These risks are mild till close to zero.
The burden concerns the arthroscopy, the joint can become stiff and the advise
is to spare the joint
Meibergdreef 9 F4-105
1105 AZ Amsterdam ZO
NL
Meibergdreef 9 F4-105
1105 AZ Amsterdam ZO
NL
Listed location countries
Age
Inclusion criteria
males/females suffering form RA according to the ACR/EULAR 2010 classification criteria
active disease das 28 * 3.2 despite adequate MTX treatment
ARA functional classes I, II and III
* 18 and * 70 years of age
stable MTX treatment (5 - 30 mg/week) for at least 28 days
inflamed knee, ankle or wrist joint
Exclusion criteria
Pregnancy;
Breastfeeding;
Subjects who are impaired, incapacitated, or incapable of completing study related assessments;
Subjects who meet diagnostic criteria for any other rheumatic disease (e.g., lupus erythematosus);
Subjects who have previously received treatment with tocilizumab;
Current use of oral corticosteroids (if exceeding a prednisone equivalent of 10 mg daily) or DMARDs other than MTX; intra-articular injections of corticosteroids 28 days or less before inclusion.
Current use of TNF blocking agents, such as etanercept, adalimumab, infliximab, golimumab or certlizumab. Washout periods are depending on pharmacokinetic profile of the various agents
Rituximab en abatacept washout
Subjects with active vasculitis of a major organ system with the exception of rheumatoid nodules.
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 | EUCTR2011-000768-86-NL |
| CCMO | NL35611.018.11 |