Masitinib for the Treatment of Severe Mast Cell Activation Syndrome

A 24-week, Multicenter, Randomized, Double Blind, Placebo-controlled, Dose-range Finding Phase II Study to Compare Efficacy and Safety of Oral Masitinib to Placebo in Treatment of Patients With Severe Mast Cell Activation Syndrome (MCAS) With Handicap Unresponsive to Optimal Symptomatic Treatment

To evaluate the efficacy and safety of two dosing schemes of oral masitinib versus matching placebo in the treatment of patients suffering from severe MCAS with handicap unresponsive to optimal symptomatic treatment.

Multicenter, double-blind, placebo-controlled trial comparing two different dosing schemes over a 24-week treatment period.

Dosing scheme #1: Oral masitinib treatment at 3 mg/kg/day for 4 weeks, then a switch to 4.5 mg/kg/day for the remainder of the treatment period, versus placebo with a matching titration scheme. Randomization 2: 1 (Masitinib MCAS: Placebo MCAS).

Dosing scheme #2: Oral masitinib treatment at 3 mg/kg/day for 4 weeks, then a switch to 4.5 mg/kg/day for 4 weeks, then a second switch to 6 mg/kg/day for the remainder of the treatment period versus placebo treatment with a matching titration scheme. Randomization 2: 1 (Masitinib MCAS: Placebo MCAS)

Inclusion Criteria include:

• Patient with mast cell activation syndrome (MCAS).
• Patient with severe symptoms over the 14-day run-in period defined as at least one of the following: Pruritus score ≥ 9; Number of flushes per week ≥ 8; Hamilton rating scale for depression (HAMD-17) score ≥ 19
• Patient with documented treatment failures of his/her handicap(s) (within last two years) with at least two of the symptomatic treatments used at optimized dose.
• Patients must be on a stable dose of Anti-H1 for a minimum of 4 weeks before screening and should remain at a stable dose throughout the study period.

Exclusion Criteria include:

• Previous treatment with any Tyrosine Kinase Inhibitor.
• Any change in the symptomatic treatment of MCAS, including systemic corticosteroids, or administration of any new treatment for MCAS within 4 weeks prior to screening.
• Patient with systemic indolent mastocytosis.
• Female patients who are pregnant or are breastfeeding.