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

Condition(s) targeted: Familial Mediterranean Fever

Intervention: Canakinumab (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Novartis Pharmaceuticals

Official(s) and/or principal investigator(s):
Novartis Pharmaceuticals, Study Director, Affiliation: Novartis Pharmaceuticals

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

Official title: An Open-label, Exploratory Study to Establish the Safety and Efficacy of 3 Months Treatment With Canakinumab in Patients With Colchicine Resistant Familial Mediterranean Fever

Study design: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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.

Secondary outcome:

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

Minimum age: 12 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

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

Istanbul Medical Faculty, Dept of Rheumatology, Capa, Istanbul, Turkey

Starting date: April 2010
Last updated: April 27, 2012