Clinical trial NCT05449444: Masitinib for the Treatment of Severe Mast Cell Activation Syndrome
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Mast Cell Activation Syndrome
Lead sponsor: AB Science
Sponsor class: INDUSTRY
First posted: 2022-07-08
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled, parallel-group, multicenter comparative study with ascending dose titrations of masitinib and matching placebo
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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)

Eligibility criteria: 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.

Primary outcomes:
measure: Confirmed response at 50%
timeFrame: 24 weeks
Secondary outcomes:
measure: Cumulative response
timeFrame: week 8 to week 24
measure: Confirmed response (75%)
timeFrame: 24 weeks
measure: Patient-Reported Outcome for Symptom Severity (PROSS)
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Weldon Spring
country: United States
facility: St Charles Clinical Research
state: Missouri
city: Amiens
country: France
facility: Centre Hospitalier Universitaire Amiens-Picardie
city: Paris
country: France
facility: Necker-Enfants Malades Hospital, Centre de référence des Mastocytoses (CEREMAST)
city: Toulouse
country: France
facility: CHU Toulouse
Study officials:
affiliation: Reference Centre for Mastocytosis (CEREMAST), Necker Hospital, Paris, France
name: Julien Rossignol, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lortholary O, Chandesris MO, Bulai Livideanu C, Paul C, Guillet G, Jassem E, Niedoszytko M, Barete S, Verstovsek S, Grattan C, Damaj G, Canioni D, Fraitag S, Lhermitte L, Georgin Lavialle S, Frenzel L, Afrin LB, Hanssens K, Agopian J, Gaillard R, Kinet JP, Auclair C, Mansfield C, Moussy A, Dubreuil P, Hermine O. Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study. Lancet. 2017 Feb 11;389(10069):612-620. doi: 10.1016/S0140-6736(16)31403-9. Epub 2017 Jan 7.
citation: Latham BD, Oskin DS, Crouch RD, Vergne MJ, Jackson KD. Cytochromes P450 2C8 and 3A Catalyze the Metabolic Activation of the Tyrosine Kinase Inhibitor Masitinib. Chem Res Toxicol. 2022 Sep 19;35(9):1467-1481. doi: 10.1021/acs.chemrestox.2c00057. Epub 2022 Sep 1.