study of efficacy and safety of canakinumab in patients with hereditary periodic fevers

Conditions: Hereditary Periodic Fevers

Summary: this study is to determine whether canakinumab is able to induce and maintain a clinically meaningful reduction of disease activity in participants with hereditary periodic fevers (hpf) compared to placebo.

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

Eligibility criteria:
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 \ 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

Keywords: canakinumab, interleukin-1, hereditary periodic fevers, auto-inflammatory diseases