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

NCT03445845 | Completed Phase 4

• 2 other identifiers: 16081852017-004700-22
• Study Type: interventional
• Target: 300
• Locations: 2 countries
• Sites: 35

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.

Conditions

Axial Spondyloarthritis

Keywords

TNF blocker; change of biotherapy

Outcome Measures

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

  24 weks

Secondary Outcomes (17)

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

  12 weeks

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

  52 weeks

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

  52 weeks

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

  24 weeks

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

  52 weeks

Study Arms (2)

targeting IL-23/17 axis

EXPERIMENTAL

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

TNF blocker

ACTIVE COMPARATOR

• 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

Secukinumab DRUG

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

targeting IL-23/17 axis

TNF blocker DRUG

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.

TNF blocker

blood specimen BIOLOGICAL

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

TNF blocker; targeting IL-23/17 axis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Ability to complete questionnaires
• Social security affiliation
• Informed written consent given

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead
• Ministry of Health, France: collaborator

Study Sites (35)

CHU d'Angers

Angers, France

Location

CHRU Besançon

Besançon, France

Location

APHP- Hôpital Avicenne

Bobigny, France

Location

CHU Bordeaux

Bordeau, France

Location

CHRU Brest

Brest, France

Location

CHU Clermont-Ferrand

Clermont-Ferrand, France

Location

CHU de Grenoble Alpes

Grenoble, France

Location

CHD Vendée

La Roche-sur-Yon, France

Location

CH Le Mans

Le Mans, France

Location

CHRU Lille

Lille, France

Location

Hôpital Saint-Philibert

Lomme, France

Location

CH Lyon SUD

Lyon, France

Location

Hôpital Edouard Herriot

Lyon, France

Location

CHRU Montpellier

Montpellier, France

Location

CHU Montpellier - 2 - Unité Clinique thérapeutique des Maladies Ostéo-Articulaires

Montpellier, France

Location

CHU Nancy

Nancy, France

Location

CHU de Nantes

Nantes, France

Location

CHU de Nice

Nice, France

Location

CHR d'Orléans

Orléans, France

Location

APHP - Hôpital Ambroise Paré

Paris, France

Location

APHP - Hôpital Bichat

Paris, France

Location

APHP - Hôpital Cochin

Paris, France

Location

APHP - Hôpital Henri Mondor

Paris, France

Location

APHP - Hôpital Lariboisière

Paris, France

Location

APHP - Hôpital Pitié-Salpétrière

Paris, France

Location

APHP - Hôpital Saint-Antoine

Paris, France

Location

APHP - Kremlin-Bicêtre

Paris, France

Location

CHU de Poitiers

Poitiers, France

Location

CHU Reims

Reims, France

Location

CHU de Rouen

Rouen, France

Location

CHU Saint-Etienne

Saint-Etienne, 42055, France

Location

CHU STRASBOURG - Hautepierre

Strasbourg, 67200, France

Location

CHU Toulouse

Toulouse, France

Location

CHRU Tours

Tours, France

Location

CH Princesse de Grace

Monaco, Monaco

Location

Related Publications (1)

• Dalix E, Marcelli C, Bejan-Angoulvant T, Finckh A, Rancon F, Akrour M, De Araujo L, Presles E, Marotte H; ROC-SpA study group. Rotation or change of biotherapy after TNF blocker treatment failure for axial spondyloarthritis: the ROC-SpA study, a randomised controlled study protocol. BMJ Open. 2024 Sep 10;14(9):e087872. doi: 10.1136/bmjopen-2024-087872.

  PMID: 39260856 DERIVED

MeSH Terms

Conditions

Axial Spondyloarthritis

Interventions

secukinumab; Tumor Necrosis Factor Inhibitors; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Intervention Hierarchy (Ancestors)

Anti-Inflammatory Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Hubert MAROTTE, MD

  CHU SAINT-ETIENNE

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2018
• First Posted: February 26, 2018
• Study Start: December 14, 2018
• Primary Completion: September 21, 2024
• Study Completion: October 1, 2024
• Last Updated: November 18, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

MO (1); FR (34)