To assess the efect of IL-17 blockade on:- the global synovial histology and inflammatory infiltration- the number and type of IL-17 producing cells in SpA synovitis- the productuion of inflammatory mediators (including other IL-17 related cytokines…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Changes in the synovial cellular and molecular pathways as indicated in the
objectives between baseline and week 12
Secondary outcome
- Stratification of these cellular and molecular changes according to the
genetic biomarkers of relevance for anti-IL17 treatment response
- Correlation between the synovial features at baseline and the clinical
response at week 12
- Comparison of the synovial molecular changes induced by anti-IL17 with the
changes induced by anti-TNF (historical samples in a similar patient population
and study setting)
- Comparison of the changes in Target to Background Ration (TBR) as an
indicator of vessel wall inflammation assessed by FDG PET/CT of the aorta and
carotid arteries
Background summary
Spondyloarthritis is the second most frequent form of chronic inflammatory
arhtritis with a prevalence of 0.5%. It effects mainly young adults and leads
to major functional handicap due to inflammation of axial and peripheral joints
as well as progressive ankylosis and structural damage.
In the late nineties we introduced TNF blockade as a successfull treatment,
but: only 50% responds well and tolerates, antiTNF does not halt the structural
damage and TNF blockade does no induce long lasting remission as almost all
patients relapse within a few weeks after interruption of the treatment. There
is thus a high unmet need for alternatives.
The rationale for anti-IL17 therapy is based on various auto-inflammatory and
auto immune models, preliminary efficacy data in psoriasis and RA and an
association of SpA with IL23R SNPs.
Preliminary efficacy data on anti-IL17 shows that it is a highly effective
treatment for signs and symptoms in SpA, moreover sub-analysis of the anti-TNF
naïve patients shows the same trend.
Study objective
To assess the efect of IL-17 blockade on:
- the global synovial histology and inflammatory infiltration
- the number and type of IL-17 producing cells in SpA synovitis
- the productuion of inflammatory mediators (including other IL-17 related
cytokines and TNF) and total tissue biopsies (ex vivo culture system)
- The synovial stromal cell signature
- The pan-genomic synovial gene expression profile
Secondary:
To compare wich molecular disease pathways are affected by IL-17 blockade and
not by TNF blockade and thereby identify molecular biomarkers which may help to
determine which patients may benefit form this treament in comparison with
anti-TNF treatment.
To assess wether AIN457 sileces vessel wall inflammation (by means of 18F-FDG
PET/CT of the carotic arteries and aorta.
Study design
Single centre, 12-week open label study in subjects with clinically active
peripheral spondylarthritis, with open label extension up to 2 years. Synovial
biopsies and FDG PET/CT of the aorta and carotid arteries will be obtained from
patients before and after 12 weeks of treatment with secukinumab.
Intervention
Secukinumab (AIN457) by monthly subcutanious injections.
Study burden and risks
Medium risk
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
-Male or non-pregnant/non-lactating females age 18-70
- Diagnosis of SpA according to ESSG criteria and/or ASAS criteria
- Active disease defined by *1 swollend and * 1 tender joint, and at least 1 swollen knee or ankle joint at baseline
Exclusion criteria
- Evidence for infectious or malignant process (on chest X ray/MRI etc)
- Pts taking opioid angalgetics
- Previous IL-17 therapy exposure
- Previous use of celldepleting therapies, biological immunomodulants (except for a.TNF)
- no more then 50% of included patients are allowed to be previously exposed to (1) TNF blocking agent
- Significant medical problems or diseases
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 | EUCTR2013-002709-79-NL |
| CCMO | NL45246.018.13 |