Masitinib for the Treatment of Severe Mast Cell Activation Syndrome

Mast Cell Activation Syndrome Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05449444
• Other study ID #: AB20006
• Secondary ID: 2021-005406-96
• Status: Recruiting
• Phase: Phase 2
• Start date: July 1, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2023
• Source: AB Science
• Contact: Clinical Study Coordinator
• Phone: +33(0)147200014
• Email: clinical[@]ab-science.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Mast Cell Activation Syndrome
• Mastocytosis
• Syndrome

Intervention

Drug:
• Masitinib 4.5 mg/kg/day
Masitinib 4.5 mg/kg/day
• Placebo
Matching placebo

Other:
• Best supportive care
Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, sodium cromoglicate, antidepressants, antileukotrienes, proton pump inhibitors, and corticosteroids.

Drug:
• Masitinib 6.0 mg/kg/day
Masitinib 6.0 mg/kg/day

Locations

Country	Name	City	State
France	Centre Hospitalier Universitaire Amiens-Picardie	Amiens
France	Necker-Enfants Malades Hospital, Centre de référence des Mastocytoses (CEREMAST)	Paris
France	CHU Toulouse	Toulouse
United States	St Charles Clinical Research	Weldon Spring	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
AB Science

Countries where clinical trial is conducted

United States,  France, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed response at 50%	Confirmed response at 50%, defined as an improvement with respect to the baseline values of 50% for Pruritus, Flushes and Depression (HAMD-17 score) which should be confirmed from the previous visit.; Handicaps at baseline defined as: pruritus score = 9; number of flushes per week = 8; HAMD-17 score = 19.	24 weeks
Secondary	Cumulative response	Cumulative (every patient visit) response at 75% on 3 handicaps (pruritus, flush, depression) from week 8 to week 24. Analysis will be performed using Generalized Estimating Equations (GEE) model with stratification.	week 8 to week 24
Secondary	Confirmed response (75%)	Confirmed response at 75%, defined as an an improvement with respect to the baseline values of 75% for Pruritus, Flushes and Depression (Hamilton Depression Rating Scale) which should be confirmed from the previous visit. The Hamilton Depression Rating Scale (HAMD-17) has 17 items and is scored between 0 and 4 points. Scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression; the maximum score being 52.	24 weeks
Secondary	Patient-Reported Outcome for Symptom Severity (PROSS)	Changes in MCAS symptom severity will also be assessed using the Patient-Reported Outcome for Symptom Severity (PROSS) questionnaire. Total and individual symptom scores will be determined at baseline and at every visit until Week 24.The PROSS questionnaire has 11 items and is scored between 0 and 10 points. A score of 0 is an absence of the symptom and a score of 10 is very severe; the maximum score being 110.	24 weeks