NCT03446209

Tocilizumab for the Treatment of Familial Mediterranean Fever

Tocilizumab for the Treatment of Familial Mediterranean Fever - A Randomized, Doubleblind, Phase II Proof of Concept Study

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: University Hospital Tuebingen · Academic / Other
• Sex: All
• Age: 18 Years – 64 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Familial Mediterranean Fever

Interventions

Type	Name	Description
DRUG	Tocilizumab Infusion RoAcemtra (EU)	Experimental arm's patients will obtain TCZ intravenously once every 4 weeks for 28 weeks
DRUG	0.9% physiological saline	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.

Timeline

• Start date: 2018-04-23
• Primary completion: 2020-10-30
• Completion: 2020-10-30
• First posted: 2018-02-26
• Last updated: 2020-11-18

Locations

3 sites across 1 country: Germany