Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis Unresponsive to Optimal Symptomatic Treatment
Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis Unresponsive to Optimal Symptomatic Treatment
The purpose of this study is to evaluate the efficacy and safety of oral masitinib versus
 placebo in the treatment of patients suffering from smouldering or indolent systemic
 mastocytosis with severe symptoms of mast cell mediator release, unresponsive to optimal
 symptomatic treatment.
Masitinib is a selective tyrosine kinase inhibitor that modulates mast cell activity via
 inhibition of c-Kit, Lyn and Fyn kinase signaling pathways. This is a multicenter,
 randomized, double-blind, placebo-controlled, 2-parallel-group, trial comparing oral
 masitinib versus placebo in the treatment of patients suffering from smouldering or indolent
 systemic mastocytosis with severe symptoms of mast cell mediator release (also referred to as
 handicaps), unresponsive to optimal symptomatic treatment. The treatment period is 24 weeks.
 Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose
 escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0
 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety
 control.
Inclusion Criteria:

 1. Patient with one of the following documented mastocytosis subtypes (variants):
 Smouldering Systemic Mastocytosis, Indolent Systemic Mastocytosis

 2. An excess of mast cells or a presence of abnormal mast cells in at least two organs
 (among skin, bone-marrow and GI Tract).

 3. Patient with documented systemic mastocytosis and evaluable disease based upon
 histological criteria

 4. Patient with documented treatment failure of his/her symptom(s) (within the past 2
 years) with at least two of the symptomatic treatments used at optimized dose: Anti
 H1, Anti H2, Proton pump inhibitor, Antidepressants, Cromoglycate Sodium,
 Antileukotriene.

 5. Patient with severe symptoms of mastocytosis over the 14-day run-in period including
 at least one among pruritus, flushes, and depression: pruritus score ≥ 9, number of
 flushes per week ≥ 8, Hamilton rating scale for depression (HAMD-17) score ≥ 19.

 Exclusion Criteria:

 1. Patient with one of the following mastocytosis: Cutaneous Mastocytosis, Systemic
 Mastocytosis with an Associated clonal Hematologic Non Mast cell lineage Disease
 (SM-AHNMD), Mast cell leukemia (MCL), Aggressive systemic mastocytosis (ASM)

 2. Previous treatment with any Tyrosine Kinase Inhibitor

 3. Treatment with any investigational agent within 8 weeks prior to screening.