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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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)

Tracking Information
First Submitted Date  ICMJE February 12, 2014
First Posted Date  ICMJE November 30, 2017
Last Update Posted Date November 30, 2017
Study Start Date  ICMJE March 2014
Actual Primary Completion Date July 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 29, 2017)
  • 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.
  • 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)
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: November 29, 2017)
  • Adverse events [ Time Frame: between day0 and 2 yrs of treatment ]
    Number of patients with adverse events as a measure of safety and tolerability
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mechanism of Action of Anti-IL17 Therapy in Peripheral Spondyloarthritis
Official Title  ICMJE Mechanism of Action Study of Anti-IL17 Treatment in Spondyloarthritis: Impact on Cellular and Molecular Pathways of Synovial Inflammation and Tissue Remodeling
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.

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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Spondylarthropathies
Intervention  ICMJE Drug: Secukinumab
anti IL17 therapy (subcutaneous)
Other Name: AIN457
Study Arms  ICMJE Experimental: Secukinumab
All patients will be treated with active treatment. (anti-IL17)
Intervention: Drug: Secukinumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 29, 2017)
20
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 2017
Actual Primary Completion Date July 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03358134
Other Study ID Numbers  ICMJE AMC__45246_MoA_aIL17
2013-002709-79 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party D.L.P. Baeten, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study Sponsor  ICMJE Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators  ICMJE Novartis
Investigators  ICMJE
Principal Investigator: dominique LP Baeten, MD PhD prof. AIDS Malignancy Consortium
PRS Account Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Verification Date November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP