Efficacy and Safety of Canakinumab in Patients With Colchicine Resistant Familial Mediterranean Fever

• To assess the effect of canakinumab with regard to percentage of patients with no attacks in month 3. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• To find the optimal dose of canakinumab for FMF in this population [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• 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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• To assess PK/PD properties of canakinumab by measuring canakinumab and IL-1beta levels before dosing [ Designated as safety issue: No ]
• To evaluate the safety and tolerability of canakinumab by monitoring adverse events and patient discontinuations due to AE [ Designated as safety issue: Yes ]

Establish the safety and efficacy of 3 months treatment with canakinumab in patients with colchicine resistant Familial Mediterranean Fever.

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.

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