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CompletedNCT03445845ROC-SPAUpdated Nov 18, 2024

Rotation or Change of Biotherapy After TNF Blocker Treatment Failure for Axial Spondyloarthritis

A Phase 4 interventional study of Secukinumab and TNF blocker in Axial Spondyloarthritis, sponsored by Centre Hospitalier Universitaire de Saint Etienne. Completed at 35 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-11-18.

Sponsored by Centre Hospitalier Universitaire de Saint Etienne · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
300
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterized by inflammatory arthritis and enthesitis involving the spine. AxSpA prevalence is around 0.17% of the French population. Tumor necrosis factor (TNF) was the first target defined in axSpA. Since one third of axSpA patients failed to the first TNF blocker, many axSpA patients received a second biological Disease-Modifying AntiRheumatic Drugs (bDMARDs). Until few months, the only choice was to use a second TNF blocker.Since 2003, pharmaceutical companies investigated efficacy of TNF blockers already used in rheumatoid arthritis. Etanercept is a fusion protein with TNF receptor type II p75 and IgG1 Fc fragment, whereas adalimumab, infliximab, and golimumab are monoclonal antibodies. Certolizumab is a fusion between a fab fragment targeting TNF and a Peg fraction. All demonstrated efficacy versus placebo in a randomized double blinded study

In case of failure to the first TNF blockers, rheumatologists will follow the "Treat-to-Target" principle. This approach already demonstrated its benefit in rheumatoid arthritis or in psoriatic arthritis. This concept was also suggested for axSpA with low levels of evidence and recommendation. So rheumatologist will provide the best treatment in case of failure to the first TNF blockers, which is a daily clinical situation. Since few months, rheumatologists have the choice between targeting IL-23/17 axis compared to a second TNF blocker.

02

Conditions studied

  • Axial Spondyloarthritis

Keywords

  • TNF blocker
  • change of biotherapy
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Active axSPA with BASDAI>4 or ASDAS>3.5, who need change in TNF blocker treatment
  • Aged over 18 years
  • Inadequate response after at least 3 months to the 1st TNF blocker
  • If non biologic DMARD treatment : stable dose for at least on month before inclusion
  • If oral corticosteroids treatment : stable dose for at least on month before inclusion
  • If NSAIDs treatment : stable dose for at least on month before inclusion
  • Ability to complete questionnaires
  • Social security affiliation
  • Informed written consent given

Exclusion criteria

Exclusion Criteria:

  • Any contra-indication to TNF blocker and/or secukinumab
  • Inflammatory bowel diseases
  • Existing pregnancy, lactation, or intended pregnancy within the next 15 months Active tuberculosis or other severe infections such as sepsis or opportunistic infections
  • Active infections, including chronic or localised infections.
  • Moderate to severe heart failure (NYHA classes III/IV)
  • Impossibility to give informed consent
  • Impossibility to be followed for 12 months
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
300 participants (actual)

Study arms

  • Experimental
    targeting IL-23/17 axis

    The experimental group (targeting IL-23/17 axis) receiving secukinumab in compliance with the marketing authorization regimen: 150 mg per week for 5 weeks, and then every month by subcutaneous injection. Blood specimen at each visits

    Drug: Secukinumab · Biological: blood specimen

  • Active comparator
    TNF blocker

    • The control group receiving a second TNF blocker in compliance with the marketing authorization regimen: The TNF blocker (originator or biosimilar) will be different to the TNF used before the inclusion and will be chose by the investigator: * infliximab: 5mg/kg per IV infusion at weeks 0, 2, 6, and then every 6 weeks, * etanercept: 50mg per week in subcutaneous injection, * adalimumab: 40mg every other week in subcutaneous injection, * certolizumab: 400mg every other week 3 times, and then 200mg every other week or 400mg per month in subcutaneous injections, * golimumab: 50mg every month in subcutaneous injection, in case of overweight (\>100kg) an inadequate response, 100mg every month is allow. Blood specimen at each visits

    Drug: TNF blocker · Biological: blood specimen

Interventions

  • DrugSecukinumab

    Secukinumab : 150 mg per week for 5 weeks, and then every month by subcutaneous injection

  • DrugTNF blocker

    TNF blocker (originator or biosimilar) : * infliximab: 5mg/kg per IV infusion at weeks 0, 2, 6, and then every 6 weeks, * etanercept: 50mg per week in subcutaneous injection, * adalimumab: 40mg every other week in subcutaneous injection, * certolizumab: 400mg every other week 3 times, and then 200mg every other week or 400mg per month in subcutaneous injections, * golimumab: 50mg every month in subcutaneous injection, in case of overweight (\>100kg) an inadequate response, 100mg every month is allow.

  • Biologicalblood specimen

    Blood specimen at each visits for measurement of bDMARS blockers concentration and anti-drug antibody concentration

05

What researchers measure

Primary outcomes

  1. Proportion of axSpA patients with a clinical response Assessments in Ankylosing Spondylitis International Society 40 (ASAS 40) at week 24

    ASAS 40 is defined as an improvement of at least 40% and absolute improvement of at least 2 units on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion: * Patient global assessment : numerical rating scale with extremes labelled "none" and "severe." * Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain." * Function : BASFI average of 10 questions measured by numerical rating scale with extremes labelled "easy" and "impossible." * Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening at all in remaining domain

    Time frame: 24 weks

Secondary outcomes

  1. Proportion of axSpA patients with a clinical response ASAS 40 at week 12

    ASAS 40 is defined as an improvement of at least 40% and absolute improvement of at least 2 units on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion: * Patient global assessment : numerical rating scale with extremes labelled "none" and "severe." * Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain." * Function : BASFI average of 10 questions measured by numerical rating scale with extremes labelled "easy" and "impossible." * Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening at all in remaining domain

    Time frame: 12 weeks

  2. Proportion of axSpA patients with a clinical response ASAS 40 at week 52

    ASAS 40 is defined as an improvement of at least 40% and absolute improvement of at least 2 units on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion: * Patient global assessment : numerical rating scale with extremes labelled "none" and "severe." * Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain." * Function : BASFI average of 10 questions measured by numerical rating scale with extremes labelled "easy" and "impossible." * Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening at all in remaining domain

    Time frame: 52 weeks

  3. Proportion of axSpA patients with a clinical response ASAS 20 at week 12

    ASAS 20 is defined as an improvement of at least 20% and absolute improvement of at least 1 unit on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion: * Patient global assessment : numerical rating scale with extremes labelled "none" and "severe." * Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain." * Function : BASFI average of 10 questions regarding measured by numerical rating scale with extremes labelled "easy" and "impossible." * Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening in a similar amount in the fourth domain

    Time frame: 52 weeks

  4. Proportion of axSpA patients with a clinical response ASAS 20 at week 24

    ASAS 20 is defined as an improvement of at least 20% and absolute improvement of at least 1 unit on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion: * Patient global assessment : numerical rating scale with extremes labelled "none" and "severe." * Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain." * Function : BASFI average of 10 questions regarding measured by numerical rating scale with extremes labelled "easy" and "impossible." * Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening in a similar amount in the fourth domain

    Time frame: 24 weeks

  5. Proportion of axSpA patients with a clinical response ASAS20 at week 52

    ASAS 20 is defined as an improvement of at least 20% and absolute improvement of at least 1 unit on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion: * Patient global assessment : numerical rating scale with extremes labelled "none" and "severe." * Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain." * Function : BASFI average of 10 questions regarding measured by numerical rating scale with extremes labelled "easy" and "impossible." * Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening in a similar amount in the fourth domain

    Time frame: 52 weeks

  6. Proportion of axSpA patients with a partial remission rate at week 12

    Partial remission is defined by values lower than 2/10 in each 4 domains: * Patient global assessment measured on a numerical rating scale with extremes labelled "none" and "severe." * Pain assessment represented by the average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain." * Function represented by BASFI average of 10 questions regarding ability to perform specific tasks as measured by numerical rating scale with extremes labelled "easy" and "impossible." * Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI regarding morning stiffness as measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours."

    Time frame: 12 weeks

  7. Proportion of axSpA patients with a partial remission rate at week 24

    Partial remission is defined by values lower than 2/10 in each 4 domains: * Patient global assessment measured on a numerical rating scale with extremes labelled "none" and "severe." * Pain assessment represented by the average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain." * Function represented by BASFI average of 10 questions regarding ability to perform specific tasks as measured by numerical rating scale with extremes labelled "easy" and "impossible." * Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI regarding morning stiffness as measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours."

    Time frame: 24 weeks

  8. Proportion of axSpA patients with a partial remission rate at week 52

    Partial remission is defined by values lower than 2/10 in each 4 domains: * Patient global assessment measured on a numerical rating scale with extremes labelled "none" and "severe." * Pain assessment represented by the average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain." * Function represented by BASFI average of 10 questions regarding ability to perform specific tasks as measured by numerical rating scale with extremes labelled "easy" and "impossible." * Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI regarding morning stiffness as measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours."

    Time frame: 52 weeks

  9. Proportion of axSpA patients with a ASDAS major improvement at week 12

    ASDAS major improvement was defined by a variation of ASDAS-CRP≥2

    Time frame: 12 weeks

  10. Proportion of axSpA patients with a ASDAS major improvement at week 24

    ASDAS major improvement was defined by a variation of ASDAS-CRP≥2

    Time frame: 24 weeks

  11. Proportion of axSpA patients with a ASDAS major improvement at week 52

    ASDAS major improvement was defined by a variation of ASDAS-CRP≥2

    Time frame: 52 weeks

  12. Proportion of axSpA patients with biological Disease-Modifying AntiRheumatic Drugs (bDMARDs) treatment at week 12

    Patient with the same bDAMRs treatment at inclusion and week 12

    Time frame: 12 weeks

  13. Proportion of axSpA patients with biological Disease-Modifying AntiRheumatic Drugs (bDMARDs) treatment at week 24

    Patient with the same biological Disease-Modifying AntiRheumatic Drug (bDAMR) treatment at inclusion and week 24

    Time frame: 24 weeks

  14. Proportion of axSpA patients with bDMARDs treatment at week 52

    Patient with the same biological Disease-Modifying AntiRheumatic Drug (bDAMR) treatment at inclusion and week 52

    Time frame: 52 weeks

  15. Number of adverse events

    Number of adverse events

    Time frame: 52 weeks

  16. Correlation between concentration of antibodies to bDMARS blockers and clinical response according to treatment

    Concentration of antibodies to bDMARS blockers is measured by Enzyme Linked ImmunoSorbent Assay (ELISA) low disease activity is defined by BASDAI \<4 and ASDAS \<2.1

    Time frame: From baseline to 52 weeks

  17. Correlation between concentration of anti-drug antibodies and clinical response according to treatment

    Concentration of anti-drug antibodies is measured by Enzyme Linked ImmunoSorbent Assay (ELISA) low disease activity is defined by BASDAI \<4 and ASDAS \<2.1

    Time frame: From baseline to 52 weeks

06

Study locations

35 sites
  • CHU d'Angers
    Angers, France
  • CHRU Besançon
    Besançon, France
  • APHP- Hôpital Avicenne
    Bobigny, France
  • CHU Bordeaux
    Bordeau, France
  • CHRU Brest
    Brest, France
  • CHU Clermont-Ferrand
    Clermont-Ferrand, France
  • CHU de Grenoble Alpes
    Grenoble, France
  • CHD Vendée
    La Roche-sur-Yon, France
  • CH Le Mans
    Le Mans, France
  • CHRU Lille
    Lille, France
  • Hôpital Saint-Philibert
    Lomme, France
  • CH Lyon SUD
    Lyon, France
  • Hôpital Edouard Herriot
    Lyon, France
  • CHRU Montpellier
    Montpellier, France
  • CHU Montpellier - 2 - Unité Clinique thérapeutique des Maladies Ostéo-Articulaires
    Montpellier, France
  • CHU Nancy
    Nancy, France
  • CHU de Nantes
    Nantes, France
  • CHU de Nice
    Nice, France
  • CHR d'Orléans
    Orléans, France
  • APHP - Hôpital Ambroise Paré
    Paris, France
  • APHP - Hôpital Bichat
    Paris, France
  • APHP - Hôpital Cochin
    Paris, France
  • APHP - Hôpital Henri Mondor
    Paris, France
  • APHP - Hôpital Lariboisière
    Paris, France
  • APHP - Hôpital Pitié-Salpétrière
    Paris, France
  • APHP - Hôpital Saint-Antoine
    Paris, France
  • APHP - Kremlin-Bicêtre
    Paris, France
  • CHU de Poitiers
    Poitiers, France
  • CHU Reims
    Reims, France
  • CHU de Rouen
    Rouen, France
  • CHU Saint-Etienne
    Saint-Étienne, 42055, France
  • CHU STRASBOURG - Hautepierre
    Strasbourg, 67200, France
  • CHU Toulouse
    Toulouse, France
  • CHRU Tours
    Tours, France
  • CH Princesse de Grace
    Monaco, Monaco
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03445845
Lead sponsor
Centre Hospitalier Universitaire de Saint Etienne
Collaborators
Ministry of Health, France
Responsible party
Sponsor
First posted
Feb 26, 2018
Start date
Dec 14, 2018
Primary completion
Sep 21, 2024
Completion
Oct 1, 2024
Last update
Nov 18, 2024

Study contacts

Hubert MAROTTE, MD
study director · CHU Saint-Etienne

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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