Study of Efficacy and Safety of Canakinumab in Patients With Hereditary Periodic Fevers

This study consists of 3 randomized cohorts (one per condition of colchicine
resistant/intolerant Familial Mediterranean Fever (crFMF), Hyper Immunoglobulin D Syndrome
(also known as mevalonate kinase deficiency (HIDS/MKD), and Tumor Necrosis Factor Receptor
Associated Periodic Syndrome (TRAPS), and 4 study epochs:

1. Epoch 1: a screening epoch to assess participant's eligibility;

2. Epoch 2: a randomized treatment epoch of 16 weeks where participants are randomized to
canakinumab 150 mg every 4 weeks (q4w) or to placebo to obtain efficacy and safety data
in a double-blind placebo controlled parallel-arm setting. This epoch contained 2
possible escape options :

1. early blinded escape option for non responders from Day 8 to Day 28 with here an
add-on dose of 150mg canakinumab followed by blinded uptitration at the next
scheduled visit (Day 29)

2. late unblinded escape option for non responders from Day 29 to Day 112; with
open-label uptitration

3. Epoch 3: a randomized withdrawal epoch of 24 weeks where canakinumab responders from the
randomized treatment epoch were re-randomized to canakinumab 150mg q8w or placebo to
assess the potential for canakinumab to maintain clinical efficacy at a reduced dosing
frequency;

4. Epoch 4: an open-label treatment epoch of 72 weeks to collect long-term

Inclusion Criteria: - Patient's written informed consent (or parent's written informed
consent in case of pediatric patient) at screening - Male and female patients at least 2
years of age at the time of the screening visit. Male and female patients >28 days but <2
years eligible for open label treatment only. - Confirmed diagnosis and active flare at
randomization - CRP >10mg/L at randomization

Exclusion Criteria: - Use of the following therapies (within varying protocol defined
timeframes): Corticosteroids, anakinra, canakinumab, rilonacept, tocilizumab, TNF
inhibitors, abatacept, tofacitinib, rituximab, leflunomide, thalidomide, cyclosporine,
intravenous immunoglobulin, 6-Merceptopurine, azathioprine, cyclophosphamide, or
chlorambucil, any other investigational biologics - History of malignancy of any organ
system (other than localized basal cell carcinoma of the skin or in - situ cervical
cancer), treated or untreated - Significant medical diseases, including but not limited to
the following: a. History of organ transplantation b. Elevated liver enzymes ≥3x ULN d.
Increase in total bilirubin e. Serious hepatic disorder (Child-Pugh scores B or C) f.
Chronic Kidney Disease g. Thyroid disease h. Diagnosis of active peptic ulcer disease i.
Coagulopathy j. Significant CNS effects including vertigo and dizziness - Any conditions or
significant medical problems which immunecompromise the patient and/or places the patient
at unacceptable risk for immunomodulatory therapy - Live vaccinations within 3 months prior
to the start of the trial, during the trial, and up to 3 months following the last dose