SpondylarthropathiesPhase 3MoA aIL-17NCT03358134
Mechanism of Action of Anti-IL17 Therapy in Peripheral Spondyloarthritis
A Phase 3 study testing Secukinumab in people with Spondylarthropathies, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Spondylarthropathies
- What is being tested?
- Secukinumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2014to Oct 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Academic Medical Center Amsterdam
Amsterdam, North Holland, 1105AZ
About this study
Official title: Mechanism of Action Study of Anti-IL17 Treatment in Spondyloarthritis: Impact on Cellular and Molecular Pathways of Synovial Inflammation and Tissue Remodeling
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.
Read the 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).
- Conditions
- Spondylarthropathies
- Being tested
- Secukinumab
- Keywords
- Peripheral Spondylarthropathies, Psoriatic arthritis, Reactive arthritis
- Medical subject headings
- Spondylarthropathies, Arthritis, Psoriatic, Arthritis, Reactive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SecukinumabDrug
Also called AIN457
anti IL17 therapy (subcutaneous)
| Study group | Role | What they receive |
|---|---|---|
| Secukinumab | Experimental | All patients will be treated with active treatment. (anti-IL17) Receives: Drug: Secukinumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biological changes induced by therapy on target tissue (synovium)
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.
Measured: week 0 and week 12
Changes of cellular infiltrate in the target tissue (synovium)
Changes in cell count measured by immunohistochemistry (on a 0-4 semi-quantitative analysis scale)
Measured: week 0 and week 12
Secondary outcomes (2)
Adverse events
Number of patients with adverse events as a measure of safety and tolerability
Measured: between day0 and 2 yrs of treatment
Vessel wall inflammation
Changes in Fludeoxyglucose (FDG18) PET/CT uptake in the vessel walls of the carotic arteries and aorta as measured by CT values
Measured: week 0 and week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2017
- Study startMar 2014
- Primary completionJul 2017
- Study completionOct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SpondylarthropathiesStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Principal investigator, D.L.P. Baeten, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- dominique LP Baeten, MD PhD prof., Principal investigator, AIDS Malignancy Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03358134
- Sponsor's protocol ID
- AMC__45246_MoA_aIL17
- Other IDs
- 2013-002709-79
- Acronym
- MoA aIL-17
- Status last verified
- Nov 2017
- First submitted
- 12 Feb 2014
- Last updated
- 30 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanism of Action Study of Anti-IL17 Treatment in Spondyloarthritis: Impact on Cellular and Molecular Pathways of Synovial Inflammation and Tissue Remodeling
- ClinicalTrials.gov ID
- NCT03358134
- Acronym / sponsor ID
- MoA aIL-17 / AMC__45246_MoA_aIL17
- Conditions
- Spondylarthropathies
- Keywords
- Peripheral Spondylarthropathies, Psoriatic arthritis, Reactive arthritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- Novartis
- Study start
- Mar 2014
- Primary completion
- Jul 2017 (actual)
- Study completion
- Oct 2017 (actual)
- First posted
- 30 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Secukinumab | Experimental | Drug: SecukinumabAll patients will be treated with active treatment. (anti-IL17) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SecukinumabAlso: AIN457anti IL17 therapy (subcutaneous) | Drug | Secukinumab |
Primary outcome
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)
2 secondary outcomes
Adverse events
Time frame: between day0 and 2 yrs of treatment
Vessel wall inflammation
Time frame: week 0 and week 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
dominique LP Baeten, MD PhD prof. principal investigator
AIDS Malignancy Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Secukinumab in people with Spondylarthropathies, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biological changes induced by therapy on target tissue (synovium) (time frame: week 0 and week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Nov 2017; AzTrials last refreshed its copy on 8 Nov 2026.