E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Familial Mediterranean Fever |
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E.1.1.1 | Medical condition in easily understood language |
Familial Mediterranean Fever |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016207 |
E.1.2 | Term | Familial mediterranean fever |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 measure the effect of canakinumab on the frequency of FMF
attacks defined as percentage of subjects with at least 50% reduction in the attack frequency during 3 month treatment period. |
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E.2.2 | Secondary objectives of the trial |
•To assess the effect of canakinumab with regard to percentage of subjects with no attacks in month 3 after treatment.
•To evaluate the safety and tolerability of canakinumab by monitoring adverse events and patient discontinuations due to AE
•To assess the change in frequency of FMF attacks during the treatment period
•To assess effect of canakinumab on the following inflammatory parameters: ESR, Creactive protein and serum amyloid A
•To assess effect of canakinumab on an acute attack
•To assess the time to relapse after 3 months of canakinumab treatment
•To assess changes in the severity (acute phase response and VAS evaluation of attack severity by patient) and duration of acute attacks during the treatment period
•To assess changes in the quality of life during study period with a generic tool SF-36
•To assess PK/PD properties of canakinumab by measuring canakinumab and IL-1beta levels before each dosing
•To find the optimal dose of canakinumab for FMF in this population |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Male and female patients between 12 and 75 years of age with active type 1 FMF disease (according to Tel-Hashomer criteria for diagnosis of FMF) despite colchicine therapy (1.5 to 2.0 mg/day).
•Patients who are intolerant to effective doses of colchicine (1.5 to 2 mg/day)
•Patients with demonstrated minimum 1 typical acute attack per month and genetic confirmation of diagnosis (with at least one of the known MEFV gene exon 10 mutations). Patients with manifested amyloidosis are excluded.
•Patients must have a historical data showing a frequency of at least 1 attack/month within the last 3 months before they can be enter the run-in period.
•Patients must have type 1 disease characterized by recurrent and short episodes of inflammation and serositis with an average of at least 1 documented acute FMF attack per month during the previous 6 months and lasting approximately 12 to 72 hours.
•Patients treated with IL-1 therapies must complete washout and have experienced at least 2 attacks since (e.g. Anakinra: 3 day washout; Rilonacept: 3 week washout)
•Patients treated with anti-TNF drugs must undergo appropriate washout. Prior to randomization, use of Etanercept must be discontinued for 4 weeks or use of Adalimumab or Infliximab must be discontinued for 8 weeks.
•Female subjects of childbearing potential must be using two acceptable methods of contraception
•Patients treated with Interferon therapies must complete 1 month washout period.
Other protocol-defined inclusion/exclusion criteria may app |
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E.4 | Principal exclusion criteria |
•Patients with end-organ dysfunction due to amyloidosis (e.g. existing biopsy proven amyloidosis or proteinuria > 0.5 gram per day)
•Patients taking steroids within 1 month prior to baseline
•Presence or history of any other inflammatory rheumatic disease
•Positive PPD test (according to local guidance) where a latent or active TB infection cannot be excluded via Quantiferon (T-Spot or radiographic imaging if needed).
•Patients who are pregnant or lactating
•Presence of any active or chronic infection or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 30 days or oral antibiotics within 14 days prior to screening
•History or a malignancy within the last 5 years, except for successfully excised squamous or basal cell carcinoma of the skin
Other protocol-defined inclusion/exclusion criteria may apply
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E.5 End points |
E.5.1 | Primary end point(s) |
To measure the effect of canakinumab on the frequency of FMF attacks defined as percentage of patients with at least 50% reduction in the attack frequency during 3 month treatment period. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•To assess the effect of canakinumab with regard to percentage of patients with no attacks in month 3.
•To find the optimal dose of canakinumab for FMF in this population
•To assess changes in the severity (acute phase response and VAS evaluation of attack severity by patient) and duration of acute attacks during the treatment period
•To assess PK/PD properties of canakinumab by measuring canakinumab and IL-1beta levels before dosing
•To evaluate the safety and tolerability of canakinumab by monitoring adverse events and patient discontinuations due to AE |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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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25-Oct-2011 (last patient completed) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |