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Mechanism of Action of Anti-IL17 Therapy in Peripheral Spondyloarthritis (MoA aIL-17)

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ClinicalTrials.gov Identifier: NCT03358134
Recruitment Status : Completed
First Posted : November 30, 2017
Last Update Posted : November 30, 2017
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
D.L.P. Baeten, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary:

The purpose of this study is to determine the mechanism of action on target tissue level of anti Interleukine-17 (anti-IL-17) an therapy in peripheral spondyloarthritis.

Patients will be treated with anti-IL-17 therapy (secukinumab) for 12 weeks and with a 2 year extension period thereafter.

At week 0 and 12 peripheral blood, synovial tissue and skin will be analysed with different techniques, including immunohistochemistry, RNA analysis and tissue culture to assess the effect of the therapy on inflammatory pathways.


Condition or disease Intervention/treatment Phase
Spondylarthropathies Drug: Secukinumab Phase 3

Detailed Description:

Background of the study:

Spondyloarthritis is the second most frequent form of chronic inflammatory arthritis 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 Tumor Necrosis Factor (TNF) blockade was introduced as a successful treatment, but: only 50% responds well and tolerates, a-TNF does not halt the structural damage and TNF blockade does not 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 Rheumatoid arthritis (RA) and an association of SpA with Interleukin 23 Receptor (IL23R) single nucleotide polymorphism (SNP).

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.

Objective of the study:

To assess molecular and cellular effects of the treatment on the synovium.

Secondary:

To compare which molecular and cellular 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 treatment in comparison with anti-TNF treatment.

To assess wether AIN457 silences vessel wall inflammation (by means of 18F-FDG PET(positron emission tomography)/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 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (18F FDG) PET/CT of the aorta and carotid arteries will be obtained from patients before and after 12 weeks of treatment with secukinumab.

Study population:

Patients with a diagnosis of spondyloarthritis according to the European Spondyloarthropathy Study Group (ESSG) or Assess Spondyloarthritis to international Society (ASAS) criteria with at least one swollen knee or ankle joint.

Intervention :

Secukinumab (AIN457) by subcutaneous injections (weekly for the first 4 weeks and every 4 weeks thereafter).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Mechanism of Action Study of Anti-IL17 Treatment in Spondyloarthritis: Impact on Cellular and Molecular Pathways of Synovial Inflammation and Tissue Remodeling
Study Start Date : March 2014
Actual Primary Completion Date : July 2017
Actual Study Completion Date : October 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Secukinumab

Arm Intervention/treatment
Experimental: Secukinumab
All patients will be treated with active treatment. (anti-IL17)
Drug: Secukinumab
anti IL17 therapy (subcutaneous)
Other Name: AIN457




Primary Outcome Measures :
  1. Biological changes induced by therapy on target tissue (synovium) [ Time Frame: week 0 and week 12 ]
    Molecular changes of the synovium as measured by expression of several cytokines/chemokines by quantitative polymerase chain reaction (qPCR) as measured by a change in cytokine expression between baseline and week 12.

  2. Changes of cellular infiltrate in the target tissue (synovium) [ Time Frame: week 0 and week 12 ]
    Changes in cell count measured by immunohistochemistry (on a 0-4 semi-quantitative analysis scale)


Secondary Outcome Measures :
  1. Adverse events [ Time Frame: between day0 and 2 yrs of treatment ]
    Number of patients with adverse events as a measure of safety and tolerability

  2. Vessel wall inflammation [ Time Frame: week 0 and week 12 ]
    Changes in Fludeoxyglucose (FDG18) PET/CT uptake in the vessel walls of the carotic arteries and aorta as measured by CT values



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 swollen 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)
  • Patients taking opioid analgetics
  • Previous IL-17 therapy exposure
  • Previous use of cell-depleting therapies, biological immunomodulators (except for TNF blockade , as 25% may have been previously treated with 1 TNF blocking agent)
  • Significant medical problems or diseases

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03358134


Locations
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Netherlands
Academic Medical Center Amsterdam
Amsterdam, Noord-Holland, Netherlands, 1105AZ
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Novartis
Investigators
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Principal Investigator: dominique LP Baeten, MD PhD prof. AIDS Malignancy Consortium
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Responsible Party: D.L.P. Baeten, Professor, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT03358134    
Other Study ID Numbers: AMC__45246_MoA_aIL17
2013-002709-79 ( EudraCT Number )
First Posted: November 30, 2017    Key Record Dates
Last Update Posted: November 30, 2017
Last Verified: November 2017
Keywords provided by D.L.P. Baeten, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Peripheral Spondylarthropathies
Psoriatic arthritis
Reactive arthritis
Additional relevant MeSH terms:
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Spondylarthritis
Spondylarthropathies
Spondylitis
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases
Arthritis
Joint Diseases