E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Schnitzler syndrome is characterized by chronic urticarial rashes and monoclonal gammopathy. Further symptoms include recurrent fever, bone and muscle pain, arthralgia and lymphadenopathy. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062908 |
E.1.2 | Term | Schnitzler's syndrome |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of canakinumab on the clinical signs and symptoms of Schnitzler Syndrome (SchS) |
|
E.2.2 | Secondary objectives of the trial |
To assess the safety of canakinumab in subjects with SchS
To assess the change in biomarkers of inflammation (C-reactive protein, serum amyloid A, erythrocyte sedimentation rate) during the treatment period with canakinumab
To assess changes in patients’ quality of life during the treatment period with canakinumab
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adults (18 years or older) Informed consent signed and dated Able to read, understand and willing to sign the informed consent form and abide with study procedures SchS diagnosis based on diagnostic criteria defined in Appendix Patients with symptomatic SchS (as defined by the physician’s global assessment with a minimum score of 8 and CRP >ULN)
|
|
E.4 | Principal exclusion criteria |
Concurrent/ongoing treatment with anakinra (Kineret®) or recent treatment within 48 hours prior to day 0 Concurrent/ongoing treatment with other biologics or recent treatment (less than 5 half lives) Concurrent/ongoing treatment with immunosuppressives (e.g. cyclosporine, methotrexate, dapsone or others) within 4 weeks or 5 half lives prior to day 0, whichever is longer Concurrent/ongoing treatment with high doses of systemic steroids (>20mg prednisolone equivalent) Evidence of recurrent or latent systemic infection such as tuberculosis Significant medical condition rendering the patient immunocompromised or not suitable for a clinical trial Treatment with a live (attenuated) virus vaccine during three months prior to day 0 and for 3 months after end of study
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with complete response (based on physician’s global assessment on overall autoinflammatory disease activity) at day 7 in the canakinumab treated group as compared to the placebo group |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Proportion of patients with partial response (based on physician’s global assessment on overall autoinflammatory disease activity) at day 7 in the canakinumab treated group as compared to the placebo group
Change in the patient based Schnitzler Activity Score (SCHAS) during the treatment period (The SCHAS combines five symptoms, i.e. urticarial rash, periodic fever, joint pain, bone/muscle pain and fatigue; daily SCHAS values will be documented using daily health assessment forms [DHAFs])
Overall efficacy (response rate) of canakinumab as determined by the physician’s global assessment of autoinflammatory disease activity for symptoms: Urticarial rash, fatigue, fever/chills, myalgia and arthralgia
Time to relapse of clinical symptoms of SchS after canakinumab treatment
Safety of patients treated with canakinumab: This includes physical examination, routine safety laboratory assessments, vital signs and adverse event reporting
Change in inflammation markers (ESR, CRP, SAA) during the treatment period
Change in the patient’s quality of life (assessed by the Dermatology Life Quality Index and SF 36) during the treatment period
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |