Treat-to-target With Secukinumab in Axial Spondyloarthritis (TRACE)

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)

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

Study Overview

• Status: Unknown
• Conditions: Ankylosing Spondylitis; Axial Spondyloarthritis
• Intervention / Treatment: Drug: Secukinumab 150 milligram [Cosentyx]

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.

• Study Type: Interventional
• Enrollment (Anticipated): 88
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Mikkel Østergaard, DMSc PhD MD; Phone Number: +45 38633015; Email: mo@dadlnet.dk
• Study Contact Backup: Name: Sengül Seven, MD; Phone Number: +45 3863 3014; Email: senguel.seven@regionh.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Not yet recruiting
    • Reumatologisk Afdeling, Aarhus Universitetshospital
    • Principal Investigator: Anne G Loft, MS DMSc
  • Frederiksberg, Denmark, 2000
    • Recruiting
    • Videncenter for Reumatologi og Rygsygdomme, Rigshospitalet - Frederiksberg
    • Principal Investigator: Bente Jensen, MD PhD
  • Glostrup, Denmark, 2600
    • Recruiting
    • Videncenter for Reumatologi og Rygsygdomme, Rigshospitalet Glostrup
    • Contact: Mikkel Østergaard, MD PhD DMSc
    • Principal Investigator: Mikkel Østergaard, MD PhD DMSc
    • Sub-Investigator: Susanne J Pedersen, MD PhD
    • Sub-Investigator: Sengül Seven, MD
    • Sub-Investigator: Inge J Sørensen, MD PhD
  • Gråsten, Denmark, 6300
    • Not yet recruiting
    • Kong Christian X´s Gigthospital
    • Principal Investigator: Oliver Hendricks, MD PhD
  • Hellerup, Denmark, 2900
    • Recruiting
    • Videncenter for Reumatologi og Rygsygdomme, Rigshospitalet - Gentofte
    • Principal Investigator: Ole R Madsen, MD PhD DMSc
  • Hillerød, Denmark, 3400
    • Not yet recruiting
    • Videncenter for Reumatologi og Rygsygdomme, Rigshospitalet - Nordsjællands Hospital Hillerød
    • Principal Investigator: Jesper Nørregaard, MD DMSc
  • Hjørring, Denmark, 9800
    • Not yet recruiting
    • Reumatologisk Afdeling, Regionshospitalet Nordjylland, Hjørring
    • Principal Investigator: Marcin Kowalski, MD PhD
  • Køge, Denmark, 4600
    • Not yet recruiting
    • Reumatologisk afdeling, Sjællands Universitetshospital, Køge
    • Principal Investigator: Bo Ejbjerg, MD PhD
  • Odense, Denmark, 5000
    • Not yet recruiting
    • Reumatologisk Afdeling, Odense Universitetshospital
    • Principal Investigator: Hans C Horn, consultant
  • Silkeborg, Denmark, 8600
    • Not yet recruiting
    • Reumatologisk Afdeling, Regionshospitalet Silkeborg
    • Principal Investigator: Rene Østgaard, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Secukinumab 150 mg 300 mg or tumor necrosis factor inhibitor; Secukinumab 150 mg sc. injection once a week for four weeks (induction phase) and thereafter once a month. If patients do not achieve ASDAS remission they get increased dosage of Secukinumab 300 mg sc. injection once a month. If still no ASDAS remission patients change to a TNF-inhibitor	Drug: Secukinumab 150 milligram [Cosentyx]; For intervention description: see arm/group description; Other Names: Secukinumab 300 milligram [Cosentyx]

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with a positive change in MRI-inflammation	Assessed with the sum of SPARCC MRI SIJ and spine inflammation indices	Comparison of week 16 and 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients in remission vs patients not in ASDAS (Ankylosing Spondylitis Disease Activity Score) remission.	as measured by remission (<1.3) / not in ASDAS remission (>1.3)	Comparison of week 16 and 24
Changes in ASDAS score (i.e. Ankylosing Spondylitis Disease Activity Score (ASDAS 0.6-7.0))	as measured by changes in ASDAS.	Evaluated from week 0 to 16 and from week 16 to 24
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 a positive change in MRI inflammation in the spine as assessed with the Canada-Denmark MRI system for assessment of inflammation.	Week 0 to 16 and week 16 to 24
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.	week 16
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)	week 16
MRI inflammation	as measured by the SPARCC (Spondyloarthritis Research Consortium of Canada) MRI sacroiliac joint and Spine Inflammation indices and the Canada-Denmark MRI system for assessment of inflammation assessed on cMRI (conventional MRI) i.e. on STIR (short tau inversion recovery) sequences on conventional and novel scan planes and on DWI (Diffusion-weighted imaging) sequences evaluated visually and based on regions of interest (ROIs).	week 16

Collaborators and Investigators

• Sponsor: Professor Mikkel Østergaard
• Collaborators: Novartis Healthcare A/S
• Investigators: Principal Investigator: Mikkel Østergaard, DMSc PhD MD, Rigshospitalet, Denmark; Study Chair: Susanne J Pedersen, MD PhD, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): January 15, 2019
• Primary Completion (ANTICIPATED): February 1, 2021
• Study Completion (ANTICIPATED): February 1, 2021

Study Registration Dates

• First Submitted: August 17, 2018
• First Submitted That Met QC Criteria: August 17, 2018
• First Posted (ACTUAL): August 21, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 3, 2019
• Last Update Submitted That Met QC Criteria: January 2, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: TRACE; 2017-004037-93 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No