Tocilizumab for the Treatment of Familial Mediterranean Fever
Condition: Familial Mediterranean Fever
MeSH terms: Brucellosis; Familial Mediterranean Fever; Hereditary Autoinflammatory Diseases; Fever
Study type: Interventional
Phase: Phase 2

Summary: 
      Adult patients with Familial Mediterranean Fever, who have active disease
    

Detailed description: 
      FMF is a rare disease, which permanently affects daily life of the patients with severe pain
      and the risk of developing a life threatening amyloidosis. Today there are only very limited
      treatment options and an ongoing highly unmet medical need for improved treatment strategies.
      This study will be the first randomized, controlled trial to assess the benefit as well as
      the safety profile of IL6 receptor inhibition wirth TCZ in patients with FMF. Elevated tissue
      and serum levels of IL-6 have been implicated in the pathogenesis of FMF. FMF attacks are
      painfull during the period of the attack but are not life- or organthreatening and usually
      can be handeled by nonsteroidal and antipyretic treatment. Amyloidos is a longtime
      complication that appears after several years of uncontrolled disease. Placebo control
      trials' data are characterized as having greater ability to distinguish between effective and
      ineffective treatments (that is, greater assay sensitivity). The concerns about placebo use
      should revolve around the issue of risk to participants, rather than around denial of
      treatment, and that in the absence of a significant risk of harm, placebo treatment is
      acceptable. In general, it is easier to achieve statistical significance in
      placebo-controlled trials, where effects tend to be larger, such that smaller numbers of
      participants need to be exposed to the investigational medication (and research costs are
      lower.) This is especially important in rare diseases like FMF. If an active control was
      itself never evaluated in a placebo-controlled trial, using it in an equivalency study, begs
      the question of its efficacy. This is the case for Canakinumab as a potential active
      comparator in FMF. No randomized controlled trial is published for this indication by now.
      Therefore, a placebo controlled study over a period of 16 weeks seems to be justifiable
      without exposing our patients to risk of serious or irreversible harm. NSAR and antipyretic
      treatment, as a rescue therapy for attacks, is possible throughout the study. In addition,
      all patients with uncontrolled active disease despite NSAR or paracetamol will drop out and
      will be treated with escape therapy, especially Canakinumab. Based on the available safety
      data in the RA program, the adverse effects of TCZ have been shown to be manageable (e.g.
      cytopenia, liver encyme elevation), reversible and usually not treatment limiting . The
      safety profile and tolerability of TCZ are expected to be similar or even better in patients
      with FMF than in patients with rheumatoid arthritis or giant cell arteritis, as the cohort of
      FMF patients is, in general, younger and shows less concomitant diaseases. Overall, the
      benefit-risk ratio of FMF patients to be treated with TCZ is judged positive.
    

Intervention name(s): Tocilizumab Infusion RoAcemtra (EU); 0.9% physiological saline
Intervention type(s): Drug; Drug
Intervention description(s): Experimental arm's patients will obtain TCZ intravenously once every 4 weeks for 28 weeks; Experimental arm's patients will obtain saline intravenously once every 4 weeks for 16 weeks. If necessary, patients will get "rescue medication" after week 16 to week 28.
Other intervention name(s): Actemra
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Multi-center, phase II, randomized, placebo-controlled, double blind proof of concept trial
Masking: Double (Participant, Investigator)
Primary purpose: Treatment