Masitinib for the Treatment of Severe Mast Cell Activation Syndrome

NCT ID: NCT05449444

Last Updated: 2023-02-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

72 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-01

Study Completion Date

2024-12-31

Brief Summary

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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

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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)

Conditions

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Mast Cell Activation Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized, double-blind, placebo-controlled, parallel-group, multicenter comparative study with ascending dose titrations of masitinib and matching placebo
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
Eligible patients will be randomized by means of a computerized central randomization system called IWRS (interactive web response system).

Study Groups

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Masitinib (4.5) & BSC

Masitinib 4.5 mg/kg/day administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC). Participants receive masitinib (3.0 mg/kg/day) for 4 weeks, given orally twice daily, with a dose escalation to 4.5 mg/kg/day for the remainder of the treatment period. Each ascending dose titration is subjected to a safety control.

Group Type EXPERIMENTAL

Masitinib 4.5 mg/kg/day

Intervention Type DRUG

Masitinib 4.5 mg/kg/day

Best supportive care

Intervention Type OTHER

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

Masitinib (6.0) & BSC

Masitinib 6.0 mg/kg/day administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC). Participants receive masitinib (3.0 mg/kg/day) for 4 weeks, given orally twice daily, with a dose escalation to 4.5 mg/kg/day for4 weeks of treatment, then a second dose escalation to 6 mg/kg/day for the remainder of the treatment period. Each ascending dose titration is subjected to a safety control.

Group Type EXPERIMENTAL

Best supportive care

Intervention Type OTHER

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

Masitinib 6.0 mg/kg/day

Intervention Type DRUG

Masitinib 6.0 mg/kg/day

Placebo & BSC

Placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC). Participants receive a matched dose placebo, given orally twice daily.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching placebo

Best supportive care

Intervention Type OTHER

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

Interventions

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Masitinib 4.5 mg/kg/day

Masitinib 4.5 mg/kg/day

Intervention Type DRUG

Placebo

Matching placebo

Intervention Type DRUG

Best supportive care

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

Intervention Type OTHER

Masitinib 6.0 mg/kg/day

Masitinib 6.0 mg/kg/day

Intervention Type DRUG

Other Intervention Names

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AB1010 Placebo Oral Tablet BSC AB1010

Eligibility Criteria

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Inclusion Criteria

* 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

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AB Science

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Julien Rossignol, MD

Role: PRINCIPAL_INVESTIGATOR

Reference Centre for Mastocytosis (CEREMAST), Necker Hospital, Paris, France

Locations

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St Charles Clinical Research

Weldon Spring, Missouri, United States

Site Status RECRUITING

Centre Hospitalier Universitaire Amiens-Picardie

Amiens, , France

Site Status RECRUITING

Necker-Enfants Malades Hospital, Centre de référence des Mastocytoses (CEREMAST)

Paris, , France

Site Status RECRUITING

CHU Toulouse

Toulouse, , France

Site Status RECRUITING

Countries

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United States France

Central Contacts

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Clinical Study Coordinator

Role: CONTACT

+33(0)147200014

References

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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.

Reference Type BACKGROUND
PMID: 28069279 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36048877 (View on PubMed)

Other Identifiers

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2021-005406-96

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AB20006

Identifier Type: -

Identifier Source: org_study_id

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