E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Schnitzler syndrome is an acquired autoinflammatory syndrome characterized by urticaria and monoclonal gammopathy, accompanied by intermittent fever, arthralgia or arthritis, bone pain and lymphadenopathy. This chronic disease severely impedes the quality of life of the patients. |
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MedDRA Classification |
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 |
Primary: To assess if canakinumab can induce complete or almost complete response in patients with symptomatic Schnitzler syndrome at Day 14. |
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E.2.2 | Secondary objectives of the trial |
Secondary: 1. To assess if canakinumab can induce complete or almost complete response in patients with symptomatic Schnitzler syndrome at Day 3 and Day 7 2. To assess if canakinumab can induce clinical remission at Day 3, Day 7 and Day 14 3. To assess if canakinumab can prevent disease relapse in patients who demonstrated complete remission at Day 14 4. To assess the change in CRP and SAA during the treatment and follow-up periods 5. To assess the change in physician and patient global assessment of disease activity during the treatment and follow-up periods 6. To assess the time to relapse after the last canakinumab dose 7. To evaluate the safety and tolerability of canakinumab in the treatment of patients with Schnitzler syndrome. 8. To assess PK/PD properties of canakinumab in patients with Schnitzler syndrome
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with a diagnosis of Schnitzler syndrome as per criteria (see Table 1). 2. Patients that have been / are treated with Anakinra must have demonstrated a partial or complete clinical response with an associated normalization of their biomarkers of inflammation (CRP). 3. Male and female patients at least 18 years of age at the time of the screening visit. 4. Patient’s informed consent. 5. Negative QuantiFERON test or negative Purified Protein Derivative (PPD) test (< 5 mm induration) at screening or within 1 month prior to the screening visit, according to the national guidelines. Patients with a positive PPD test (≥ 5 mm induration) at screening may be enrolled only if they have either a negative chest x-ray or a negative QuantiFERON test (QFT-TB G In-Tube). 6. Adequate contraception in premenopausal females |
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E.4 | Principal exclusion criteria |
1. Pregnant or nursing (lactating) women 2. History of being immunocompromised, including a positive HIV at screening (ELISA and Western blot). 3. Serologic evidence of hepatitis B or C infection 4. Live vaccinations within 3 months prior to the start of the trial, during the trial, and up to 3 months following the last dose 5. History of significant medical conditions, which in the Investigator’s opinion would exclude the patient from participating in this trial 6. History of recurrent and/or evidence of active bacterial, fungal, or viral infection(s) 7. Use of the following therapies: • Anakinra within 24 hours prior to Baseline visit • Corticosteroids (oral prednisone (or equivalent)) > 1.0 mg/kg/day (or greater than the maximum of 60 mg/day for children over 60 kg) within 3 days prior to the Baseline visit • Intra-articular, peri-articular or intramuscular corticosteroid injections within 4 weeks prior to the Baseline visit • Any other investigational biologics within 8 weeks prior to the Baseline visit • Any other investigational drugs, other than investigational biologic treatment, within 30 days (or 3 months for investigational monoclonal antibodies) or 5 half-lives prior to the Baseline visit, whichever is longer 8. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of patients with a complete or almost complete response in patients with symptomatic Schnitzler syndrome at Day 14 after canakinumab administration.
Secondary: 1. To assess if canakinumab can induce complete or almost complete response in patients with symptomatic Schnitzler syndrome at Day 3 and Day 7 2. To assess if canakinumab can induce clinical remission at Day 3, Day 7 and Day 14 3. To assess if canakinumab can prevent disease relapse in patients who demonstrated complete remission at Day 14 4. To assess the change in CRP and SAA during the treatment and follow-up periods 5. To assess the change in physician and patient global assessment of disease activity during the treatment and follow-up periods 6. To assess the time to relapse after the last canakinumab dose 7. To evaluate the safety and tolerability of canakinumab in the treatment of patients with Schnitzler syndrome. 8. To assess PK/PD properties of canakinumab in patients with Schnitzler syndrome
Exploratory: 1. To explore the changes in patient quality of life during canakinumab treatment in patients with Schnitzler syndrome by using RAND-36, a modified version of the Medical Outcome Short Form (36) Health Survey (SF-36®). 2. To explore potential biomarkers and pharmacogenomic characterization of these patients at baseline as predictors of total clinical response with canakinumab treatment
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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 | Yes |
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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | Information not present in EudraCT |
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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Canakinumab will be administered to the patients for 6 months with a maximum follow-up period of 6 months. Patients who experience serious adverse events possibly attributable to Canakinumab as determined by the investigator will discontinue its use immediately. Patients who experience a disease flare which is persistent or progressive even though an extra 150mg dose was provided, will be considered treatment failures and will revert to their original treatment (e.g. anakinra). |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
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 |