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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

Brief 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.

Detailed Summary:

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

Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: Percentage of Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16weeks) [ Time Frame: 16 weeks ]

Resolution of the initial disease flare is defined as: Physical Global Assessment of Disease activity (PGA) <2 and C-reactive protein (CRP) within normal range (<= 10 mg/L) or reduction by at least 70% from baseline. The PGA was evaluated by the investigator based on a 5-point scale: 0 = None (no) disease associated with clinical signs and symptoms; 1 = minimal disease associated signs and symptoms; 2 = mild disease associated signs and symptoms; 3 = moderate disease associated signs and symptoms; and 5 = severe disease associated signs and symptoms.


Original Primary Outcome: Proportion of participants with resolution of initial flare at time of the randomization and absence of new flares [ Time Frame: 16 weeks ]

To demonstrate significant reduction of disease activity with canakinumab versus placebo


Current Secondary Outcome:

  • Percentage of Participants Who Achieve Physician's Global Assessment < 2 [ Time Frame: 16 weeks ]
    The PGA was evaluated by the investigator based on a 5-point scale: 0 = None (no) disease associated with clinical signs and symptoms; 1 = minimal disease associated signs and symptoms; 2 = mild disease associated signs and symptoms; 3 = moderate disease associated signs and symptoms; and 5 = severe disease associated signs and symptoms.
  • Percentage of Participants With the Serologic Remission [ Time Frame: 16 weeks ]
    Serologic remission was defined as C-reactive protein <= 10 mg/L.
  • Percentage of Participants With Normalized Serum Amyloid A (SAA) Level [ Time Frame: 16 weeks ]
    Normalized SAA was defined as SAA <= 10 mg/L.


Original Secondary Outcome:

  • Percentage of participants who achieve Physician's global assessment < 2 [ Time Frame: 16 weeks ]
    Assessment of Physician's global assessment
  • Percentage of participantswith the serologic remission [ Time Frame: 16 weeks ]
    Normalization of C-reactive protein, Serum Amyloid A


Information By: Novartis

Dates:
Date Received: February 7, 2014
Date Started: June 28, 2014
Date Completion: June 28, 2017
Last Updated: May 16, 2017
Last Verified: May 2017