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)

• Register: EUCTR
• Last refreshed on: 19 February 2024
• Main ID: EUCTR2017-004037-93-DK
• Date of registration: 07/11/2017
• Prospective Registration: Yes
• Primary sponsor: Afdeling for Rygkirurgi, Led- og Bindevævssygdomme ; Rigshospitalet - Glostrup
• Public 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)
• Scientific 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)
• Date of first enrolment: 17/01/2018
• Target sample size: 88
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004037-93
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Dose will be increased or maintained after predetermined intervals depending on remission If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Denmark

Contacts

• Name: Information desk at entrance 5
• Affiliation: Videncenter for Reumatologi og Rygsygdomme, Rigshospitalet

• Name: Information desk at entrance 5
• Affiliation: Videncenter for Reumatologi og Rygsygdomme, Rigshospitalet

Key inclusion & exclusion criteria

Inclusion criteria:
1) Diagnosis of axSpA according to the ASAS criteria and/or AS according to the modified New York criteria as judged by a 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 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 sDMARDs (syntetic DMARDs) 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

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 IL-17 or IL-17 receptor
5) Previous exposure to TNF inhibitor or drug targeting TNF.
6) Previous exposure to other types of bDMARDs than TNF inhibitor (e.g. anti-interlukin 1, anti-interleukin 6, anti-interleukin 12/23, anti-interleukin 23, anti-CD20, co-stimulation inhibitors, JAK-inhibitors etc).
7) Patients taking high-potency opioid analgesics (e.g. methadone, hydromorphone, morphine)
8) Any change in the dose of oral corticosteroids in the last 4 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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Axial spondyloarthritis and ankylosing spondylitis

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: Cosentyx
Product Name: Cosentyx
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Secukinumab
CAS Number: 1229022-83-6
Other descriptive name: SECUKINUMAB
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 150-300

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: After completion of the last patient visit in the study

Primary end point(s): The primary endpoint is defined as the proportion of patients with an improvement in MRI inflammation from week 16 to 24. This is defined as measured a positive change in MRI inflammation score =2 in the SIJs and spine, as assessed with the sum of SPARCC MRI SIJ and spine inflammation indices

Main Objective: To compare reductions in MRI inflammation in the SIJs and spine from week 16 to 24 in patients who at week 16 are in ASDAS remission (defined as ASDAS inactive disease i.e. ASDAS<1.3) (i.e. continue sc. secukinumab 150 mg monthly) vs. not in ASDAS remission (i.e. increase sc. secukinumab 300 mg monthly).

Secondary Objective: Several objectives, among others:

To compare changes in ASDAS and in MRI inflammation in the SIJs 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 to sc. secukinumab 300 mg monthly).

To compare changes in ASDAS and in MRI inflammation in the SIJs and spine from week 0 to 16 in patients who at week 16 are in ASDAS remission vs. not in ASDAS remission.

To describe the temporal changes on cMRI in MRI inflammation and structural lesions in the SIJs and spine from week 0 to week 56 in patients treated with secukinumab (cf. “treatment arms”).

Secondary Outcome(s)

Secondary end point(s): 1) Proportion of patients at week 16 and 24 who are in ASDAS remission respectively not in ASDAS remission.
2) Changes in ASDAS score from week 16 to 24 and from week 0 to 16, respectively.
3) Proportion of patients improving from week 16 to 24 (as measured by a positive change in MRI inflammation in the spine as assessed with the Canada-Denmark MRI system for assessment of inflammation).
4) Changes in MRI inflammation scores from week 0 to 16 and week 16 to 24, respectively (as measured by the SPARCC MRI SIJ and Spine Inflammation indices and the Canada-Denmark MRI system for assessment of inflammation).
5) Changes in scores/anatomical location of MRI lesions in the spine (as measured by the Canada-Denmark MRI system for assessment of inflammation, fat metaplasia, erosion, and new bone formation).
6) Changes in scores/anatomical location of MRI lesions in the SIJs (as measured by the SPARCC MRI SIJ Inflammation Index and SPARCC SIJ Structural Score (SSS)
7) MRI inflammation (as measured by the SPARCC MRI SIJ and Spine Inflammation indices and the Canada-Denmark MRI system for assessment of inflammation assessed on cMRI i.e. on STIR sequences on conventional and novel scan planes and on DWI sequences evaluated visually and based on regions of interest (ROIs)).

Timepoint(s) of evaluation of this end point: After completion of the last patient visit in the study

Secondary ID(s)

TRACE

Source(s) of Monetary Support

Novartis Healthcare A/S

Ethics review

Status: Approved
Approval date: 17/01/2018
Contact: