Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    roc-spa
Previous Study | Return to List | Next Study

Rotation or Change of Biotherapy After TNF Blocker Treatment Failure for Axial Spondyloarthritis (ROC-SPA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03445845
Recruitment Status : Recruiting
First Posted : February 26, 2018
Last Update Posted : July 27, 2021
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Saint Etienne

Brief 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.


Condition or disease Intervention/treatment Phase
Axial Spondyloarthritis Drug: Secukinumab Drug: TNF blocker Biological: blood specimen Phase 4

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Rotation or Change of Biotherapy After TNF Blocker Treatment Failure for Axial Spondyloarthritis
Actual Study Start Date : December 14, 2018
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : November 2023

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

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

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

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.

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




Primary Outcome Measures :
  1. Proportion of axSpA patients with a clinical response Assessments in Ankylosing Spondylitis International Society 40 (ASAS 40) at week 24 [ Time Frame: 24 weks ]

    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


Secondary Outcome Measures :
  1. Proportion of axSpA patients with a clinical response ASAS 40 at week 12 [ Time Frame: 12 weeks ]

    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

  2. Proportion of axSpA patients with a clinical response ASAS 40 at week 52 [ Time Frame: 52 weeks ]

    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

  3. Proportion of axSpA patients with a clinical response ASAS 20 at week 12 [ Time Frame: 52 weeks ]

    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

  4. Proportion of axSpA patients with a clinical response ASAS 20 at week 24 [ Time Frame: 24 weeks ]

    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

  5. Proportion of axSpA patients with a clinical response ASAS20 at week 52 [ Time Frame: 52 weeks ]

    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

  6. Proportion of axSpA patients with a partial remission rate at week 12 [ Time Frame: 12 weeks ]

    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."

  7. Proportion of axSpA patients with a partial remission rate at week 24 [ Time Frame: 24 weeks ]

    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."

  8. Proportion of axSpA patients with a partial remission rate at week 52 [ Time Frame: 52 weeks ]

    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."

  9. Proportion of axSpA patients with a ASDAS major improvement at week 12 [ Time Frame: 12 weeks ]
    ASDAS major improvement was defined by a variation of ASDAS-CRP≥2

  10. Proportion of axSpA patients with a ASDAS major improvement at week 24 [ Time Frame: 24 weeks ]
    ASDAS major improvement was defined by a variation of ASDAS-CRP≥2

  11. Proportion of axSpA patients with a ASDAS major improvement at week 52 [ Time Frame: 52 weeks ]
    ASDAS major improvement was defined by a variation of ASDAS-CRP≥2

  12. Proportion of axSpA patients with biological Disease-Modifying AntiRheumatic Drugs (bDMARDs) treatment at week 12 [ Time Frame: 12 weeks ]
    Patient with the same bDAMRs treatment at inclusion and week 12

  13. Proportion of axSpA patients with biological Disease-Modifying AntiRheumatic Drugs (bDMARDs) treatment at week 24 [ Time Frame: 24 weeks ]
    Patient with the same biological Disease-Modifying AntiRheumatic Drug (bDAMR) treatment at inclusion and week 24

  14. Proportion of axSpA patients with bDMARDs treatment at week 52 [ Time Frame: 52 weeks ]
    Patient with the same biological Disease-Modifying AntiRheumatic Drug (bDAMR) treatment at inclusion and week 52

  15. Number of adverse events [ Time Frame: 52 weeks ]
    Number of adverse events

  16. Correlation between concentration of antibodies to bDMARS blockers and clinical response according to treatment [ Time Frame: From baseline to 52 weeks ]
    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

  17. Correlation between concentration of anti-drug antibodies and clinical response according to treatment [ Time Frame: From baseline to 52 weeks ]
    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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03445845


Contacts
Layout table for location contacts
Contact: Hubert MAROTTE, MD 04 77 12 76 49 ext +33 hubert.marotte@chu-st-etienne.fr
Contact: Florence RANCON florence.rancon@chu-st-etienne.fr

Locations
Show Show 32 study locations
Sponsors and Collaborators
Centre Hospitalier Universitaire de Saint Etienne
Ministry of Health, France
Investigators
Layout table for investigator information
Study Director: Hubert MAROTTE, MD CHU Saint-Etienne
Layout table for additonal information
Responsible Party: Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier: NCT03445845    
Other Study ID Numbers: 1608185
2017-004700-22 ( EudraCT Number )
First Posted: February 26, 2018    Key Record Dates
Last Update Posted: July 27, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:
TNF blocker
change of biotherapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases
Arthritis
Joint Diseases
Tumor Necrosis Factor Inhibitors
Anti-Inflammatory Agents