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

Axial Spondyloarthritis Clinical Trial

— ROC-SPA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03445845
• Other study ID #: 1608185
• Secondary ID: 2017-004700-22
• Status: Recruiting
• Phase: Phase 4
• Start date: December 14, 2018
• Est. completion date: November 2025

Study information

• Verified date: June 2024
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: Hubert MAROTTE, MD
• Phone: 04 77 12 76 49
• Email: hubert.marotte[@]chu-st-etienne.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: November 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Axial Spondyloarthritis
• Spondylarthritis
• Spondylitis

Intervention

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

Locations

Country	Name	City	State
France	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
France	CHU STRASBOURG - Hautepierre	Strasbourg
France	CHU Toulouse	Toulouse
France	CHRU Tours	Tours
Monaco	CH Princesse de Grace	Monaco

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne	Ministry of Health, France

Countries where clinical trial is conducted

France,  Monaco, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	24 weks
Secondary	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	12 weeks
Secondary	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	52 weeks
Secondary	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	52 weeks
Secondary	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	24 weeks
Secondary	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	52 weeks
Secondary	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."	12 weeks
Secondary	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."	24 weeks
Secondary	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."	52 weeks
Secondary	Proportion of axSpA patients with a ASDAS major improvement at week 12	ASDAS major improvement was defined by a variation of ASDAS-CRP=2	12 weeks
Secondary	Proportion of axSpA patients with a ASDAS major improvement at week 24	ASDAS major improvement was defined by a variation of ASDAS-CRP=2	24 weeks
Secondary	Proportion of axSpA patients with a ASDAS major improvement at week 52	ASDAS major improvement was defined by a variation of ASDAS-CRP=2	52 weeks
Secondary	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	12 weeks
Secondary	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	24 weeks
Secondary	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	52 weeks
Secondary	Number of adverse events	Number of adverse events	52 weeks
Secondary	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	From baseline to 52 weeks
Secondary	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	From baseline to 52 weeks