Clinical trial NCT03639740: Treat-to-target With Secukinumab in Axial Spondyloarthritis
Official title: TReat-to-tArget (T2T) With seCukinumab in Axial Spondyloarthritis. IdEntification of MRI and Biochemical Biomarkers for Disease Activity, Treatment Response and Structural Damage Progression (the TRACE Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Axial Spondyloarthritis
Ankylosing Spondylitis
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Novartis Healthcare A/S
First posted: 2018-08-21
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Intervention model description: Dose will be increased or maintained after predetermined intervals depending on remission
Primary purpose: TREATMENT

Brief summary: A study of axSpA and AS receiving Secukinumab in a treat-to-target strategy.

Detailed description: Comparison of reductions in MRI inflammation in the sacroiliac joints and spine from week 16 to 24 in patients who at week 16 are in ASDAS remission (i.e. continue sc. secukinumab 150 mg monthly) vs. not in ASDAS remission (i.e. increase sc. secukinumab 300 mg monthly). ASDAS remission is defined as ASDAS inactive disease i.e. ASDAS\<1.3.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of axial spondyloarthritis (axSpA) according to the ASAS (Assessment of Spondyloarthritis International Society) criteria and/or ankylosing spondylitis (AS) according to the modified New York criteria as judged by a spondyloarthritis (SpA) rheumatologist (regarding imaging in the criteria, see below).
2. Active inflammation on MRI of the SIJs and/or spine as evaluated by a central SpA imaging expert and/or radiographic modified New York criteria fulfilled as judged by a central SpA imaging expert.
3. Active disease defined as ASDAS ≥ 2.1 (ASDAS high disease activity).
4. Total back pain as measured on a visual analogue scale (VAS) scale ≥ 4 0 mm (0-100 mm) at baseline.
5. Clinical indication for a biologic drug as assessed by the treating physician.
6. Patients should have received at least 2 different NSAIDs at the highest recommended dose for at least 2 weeks each with an inadequate response or failure to respond, or less if therapy had to be reduced due to intolerance, toxicity or contraindications.
7. Patients on NSAIDs at inclusion should stay on a stable dose from at least 2 weeks before the baseline MRI scans are performed and to the week 24 visit.
8. Patients on synthetic disease-modifying anti-rheumatic drugs (sDMARDs) at inclusion should stay on a stable dose from at least 4 weeks before initiation of secukinumab to the week 24 visit.
9. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study and must provide written, signed and dated informed consent before any study assessment is performed.
10. Male or female patients at least 18 years and less than 70 years of age.
11. Sufficient contraception for women.
12. Age ≥18 to \<70 years.
13. Capable of giving informed consent.
14. Capable of complying with the examination programme of the protocol.

Exclusion Criteria:

1. Contraindications for secukinumab (described in protocol).
2. Contraindication for TNF inhibitor (described in protocol).
3. Contraindication for MRI (described in protocol).
4. Previous exposure to secukinumab or other biologic drug directly targeting interleukin-17 or interleukin-17 receptor.
5. Previous exposure to TNF inhibitor or drug targeting TNF.
6. Previous exposure to other types of biological disease-modifying anti-rheumatic drugs (bDMARDs) than TNF inhibitor.
7. Patients taking high-potency opioid analgesics (e.g. methadone, hydromorphone, morphine)
8. Any change in the dose of oral corticosteroids in the last 8 weeks prior to the baseline visit or use of i.v. intramuscular or intra-articular corticosteroid during the last 8 weeks prior to the enrollment visit.
9. Use of any investigational drug and/or devices within 4 weeks before randomization or a period of 5 half-lives of the investigational drug, whichever is longer.
10. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
11. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during the entire study or longer if required by locally approved prescribing information (e.g. 20 weeks in EU).
12. Known recent drug or alcohol abuse.
13. Incapable of complying with the examination programme for physical or mental reasons.
14. Failure to provide written consent

Primary outcomes:
measure: Proportion of patients with a positive change in MRI-inflammation
timeFrame: Comparison of week 16 and 24
Secondary outcomes:
measure: Proportion of patients in remission vs patients not in ASDAS (Ankylosing Spondylitis Disease Activity Score) remission.
timeFrame: Comparison of week 16 and 24
measure: Changes in ASDAS score (i.e. Ankylosing Spondylitis Disease Activity Score (ASDAS 0.6-7.0))
timeFrame: Evaluated from week 0 to 16 and from week 16 to 24
measure: Changes in MRI inflammation scores from week 0 to 16 and week 16 to 24, respectively.
timeFrame: Week 0 to 16 and week 16 to 24
measure: Changes in scores/anatomical location of MRI lesions in the spine
timeFrame: week 16
measure: Changes in scores/anatomical location of MRI lesions in the SIJs
timeFrame: week 16
measure: MRI inflammation
timeFrame: week 16
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Reumatologisk Afdeling, Aarhus Universitetshospital
city: Frederiksberg
country: Denmark
facility: Videncenter for Reumatologi og Rygsygdomme, Rigshospitalet - Frederiksberg
city: Glostrup
country: Denmark
facility: Videncenter for Reumatologi og Rygsygdomme, Rigshospitalet Glostrup
city: Gråsten
country: Denmark
facility: Kong Christian X´s Gigthospital
city: Hellerup
country: Denmark
facility: Videncenter for Reumatologi og Rygsygdomme, Rigshospitalet - Gentofte
city: Hillerød
country: Denmark
facility: Videncenter for Reumatologi og Rygsygdomme, Rigshospitalet - Nordsjællands Hospital Hillerød
city: Hjørring
country: Denmark
facility: Reumatologisk Afdeling, Regionshospitalet Nordjylland, Hjørring
city: Køge
country: Denmark
facility: Reumatologisk afdeling, Sjællands Universitetshospital, Køge
city: Odense
country: Denmark
facility: Reumatologisk Afdeling, Odense Universitetshospital
city: Silkeborg
country: Denmark
facility: Reumatologisk Afdeling, Regionshospitalet Silkeborg
Study officials:
affiliation: Rigshospitalet, Denmark
name: Mikkel Østergaard, DMSc PhD MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Susanne J Pedersen, MD PhD
role: STUDY_CHAIR
References: