A 24-week With Possible Extension, Prospective, Multicentre, Randomized, Double Blind, Placebo-controlled, 2-parallel Group With a Randomization 1:1, Phase III Study to Compare Efficacy and Safety of Masitinib at 6 mg/kg/Day to Placebo in Treatment of Patients With Smouldering Systemic, Indolent Systemic or Cutaneous Mastocytosis With Handicap

Inclusion Criteria:

1. Patient with one of the following documented mastocytosis as per WHO classification:
Smouldering Systemic Mastocytosis, Indolent Systemic Mastocytosis, Cutaneous
Mastocytosis

2. Patient with documented mastocytosis and evaluable disease based upon histological
criteria: typical infiltrates of mast cells in a multifocal or diffuse pattern in
skin and/or bone marrow biopsy

3. Patient with documented treatment failure of his/her handicap(s) with at least one of
the following therapy used at optimized dose: Anti H1, Anti H2, Proton pump
inhibitor, Osteoclast inhibitor, Cromoglycate Sodium, Antileukotriene

4. Handicapped status defined as at least two of the following handicaps, including at
least one among pruritus, flushes, depression and asthenia: pruritus score ≥ 6,
number of flushes per week ≥ 7, Hamilton rating scale (depression) ≥ 10, number of
stools per day ≥ 4, number of mictions per day ≥ 8, Fatigue Impact Scale total score
(asthenia) ≥ 40

5. Patients with OPA > 2 (moderate to intolerable general handicap)

6. Male or female patient with age ≥ 18 years

Exclusion Criteria:

1. Patient with one of the following 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. Patient presenting with at least one of the following feature: ischemic heart
disease, cardiac failure, conduction disorders or arrythmia

4. Patient with any condition that the physician judges could be detrimental to subjects
participating in this study; including any clinically important deviations from
normal clinical laboratory values or concurrent medical events Previous treatment

5. Change in the symptomatic treatment of mastocytosis or administration of any new
treatment of mastocytosis within 4 weeks prior to baseline

6. Treatment with any investigational agent within 4 weeks prior to baseline