E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
non-radiographic axial spondyloarthritis |
spondyloarthrite axiale non radiographique active |
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E.1.1.1 | Medical condition in easily understood language |
non-radiographic axial spondyloarthritis |
spondyloarthrite axiale non radiographique active |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076297 |
E.1.2 | Term | Non-radiographic axial spondyloarthritis |
E.1.2 | System Organ Class | 100000004859 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate superiority of secukinumab 150 mg s.c., with or without loading, over placebo at Week 16, based on the proportion of patients achieving an ASAS40 response (Assessment of SpondyloArthritis International Society criteria). |
Démontrer la supériorité du sécukinumab 150 mg en sous-cutanée (s.c.) avec ou sans dose de charge versus placebo à la semaine 16, basé sur la proportion de patients répondeurs ASAS40 (Assessment of Spondyloarthritis International Society criteria). |
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E.2.2 | Secondary objectives of the trial |
-To demonstrate that the efficacy of secukinumab 150 mg s.c., with or without loading, at Week 16 is superior to placebo based on:
• the proportion of patients meeting the ASAS 5/6 response criteria
• the change from baseline in total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
• the proportion of patients achieving BASDAI 50
• the change from baseline of high sensitivity C-Reactive Protein (hsCRP)
• the change from baseline in Short Form-36 Physical Component Summary (SF-36 PCS)
• the proportion of subjects achieving an ASAS20 response
• the change from baseline in total Bath Ankylosing Spondylitis Functional Index (BASFI)
• the change from screening in SI joint edema on MRI
• the proportion of patients achieving ASAS partial remission
-Overall safety and tolerability of secukinumab
|
Démontrer que l'efficacité du sécukinumab 150 mg s.c., avec ou sans dose de charge, versus placebo, à la semaine 16 est superieur, selon les critères suivants :
- la proportion de patients répondeurs ASAS5/6,
- l’évolution du score Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) total par rapport à la baseline,
- la proportion de patients atteignant le BASDAI50,
- l’évolution du taux de Protéine C-Réactive hypersensible (hsCRP) par rapport à la baseline,
- l’évolution de la composante physique du SF-36 « Physical Component Summary » (SF-36 PCS) par rapport à la baseline,
- la proportion de patients répondeurs ASAS20,
- l’évolution du score Bath Ankylosing Spondylitis Functional Index (BASFI) par rapport à la baseline,
- l’évolution de l’atteinte œdémateuse des articulations sacro-iliaques (SI) par rapport à la sélection, à l'IRM,
- la proportion de patients répondeurs ASAS rémission partielle,
Evaluer la sécurité d’emploi et la tolérance globale du sécukinumab.
|
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or non-pregnant, non-nursing female patients at least 18 years of age
• Diagnosis of axSpA according to ASAS axSpA criteria
• Objective signs of inflammation (MRI or abnormal CRP)
• Active axSpA as assessed by total BASDAI >=4 cm
• Spinal pain as measured by BASDAI question #2 ≥ 4 cm (0-10 cm) at baseline
• Total back pain as measured by VAS ≥ 40 mm (0-100 mm) at baseline
• Patients should have been on at least 2 different NSAIDs with an inadequate response
• Patients who have been on a TNFα inhibitor (not more than one) must have experienced an inadequate response
• Other protocol-defined inclusion criteria may apply |
• Homme ou femme (hors grossesse et allaitement) âgés d'au moins 18 ans,
• Diagnostic de SpA axiale conformément aux critères ASAS axSpA
• Signes objectifs d'inflammation
• SpA axiale active : BASDAI total ≥ 4 cm
• Douleur rachidienne : BASDAI question #2 ≥ 4 cm (0-10 cm) à la baseline,
• Intensité de la douleur rachidienne, mesurée par Echelle Visuelle Analogique (EVA) ≥ 40 mm (0- 100 mm) à la baseline,
• Les patients traités par au moins 2 differents AINS avec une réponse insuffisante
• Les patients traités par un anti-TNFα (pas plus d'un) doivent avoir eu une réponse insuffisante .
• Autres critères d'inclusion définis par le protocole peuvent s'appliquer |
|
E.4 | Principal exclusion criteria |
• Patients with radiographic evidence for sacroiliitis, grade ≥ 2 bilaterally or grade ≥ 3 unilaterally
• Inability or unwillingness to undergo MRI
• Chest X-ray or MRI with evidence of ongoing infectious or malignant process
• Patients taking high potency opioid analgesics
• Previous exposure to secukinumab or any other biologic drug directly targeting IL-17 or IL-17 receptor
• Pregnant or nursing (lactating) women
• Other protocol-defined exclusion criteria may apply |
• Des patients avec signe radiographique de sacro-iliite bilatérale grade ≥ 2 ou unilatérale grade ≥ 3 2.
• Incapacité ou refus de réaliser une IRM
• Radiographie du thorax ou IRM présentant des signes d’une infection active ou d’un cancer,
• Des patients utilisand de très puissants analgésiques opioïdes
• Exposition antérieure au sécukinumab ou à tout autre médicament biologique ciblant directement l’IL-17 ou le récepteur de l’IL-17
• Des femmes enceintes ou allaitant
• Autres critères d'exclusion définis par le protocole peuvent s'appliquer |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of participants who achieved an ASAS 40 response (Assessment of SpondyloArthritis International Society criteria) |
La proportion de patients répondeurs ASAS40 (Assessment of Spondyloarthritis International Society criteria). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- The proportion of participants who achieved an ASAS 5/6 (a)
- Change in BASDAI over time (a)
- The proportion of patients to achieve a BASDAI 50 response (a)
- Change in hsCRP over time (a)
- Change in SF-36 physical Component Summary over time (a)
- The proportion of participants who achieved an ASAS 20 response (a)
- Change in BASFI over time (a)
- Change in SI Joint Edema (a)
- The proportion of patients who achieved an ASAS partial remission (a)
- Safety and tolerability (b) |
- la proportion de patients répondeurs ASAS5/6 (a),
- l’évolution du score Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) total par rapport à la baseline (a)
- la proportion de patients atteignant le BASDAI50 réponse (a)
- l’évolution du taux de Protéine C-Réactive hypersensible (hsCRP) par rapport à la baseline (a)
- l’évolution de la composante physique du SF-36 « Physical Component Summary » (SF-36 PCS) par rapport à la baseline (a)
- la proportion de patients répondeurs ASAS20 réponse (a)
- l’évolution du score Bath Ankylosing Spondylitis Functional Index (BASFI) par rapport à la baseline (a)
- l’évolution de l’atteinte œdémateuse des articulations sacro-iliaques (SI) par rapport à la sélection, à l'IRM (a)
- la proportion de patients répondeurs ASAS rémission partielle (a)
- la sécurité et la tolerance (b) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
(a) Week 16
(b) Week 112 |
(a) semaine 16
(b) semaine 112 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 105 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
Bulgaria |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Italy |
Japan |
Netherlands |
Norway |
Poland |
Portugal |
Russian Federation |
Spain |
Sweden |
Switzerland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |