Masitinib for the Treatment of Severe Mast Cell Activation Syndrome

NCT05449444 | Unknown Phase 2 DMC FDA Drug

• 2 other identifiers: AB200062021-005406-96
• Study Type: interventional
• Target: 72
• Locations: 2 countries
• Sites: 4

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.

Conditions

Mast Cell Activation Syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Cumulative response

  week 8 to week 24

• Confirmed response (75%)

  24 weeks

• Patient-Reported Outcome for Symptom Severity (PROSS)

  24 weeks

Study Arms (3)

Masitinib (4.5) & BSC

EXPERIMENTAL

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.

Drug: Masitinib 4.5 mg/kg/day; Other: Best supportive care

Masitinib (6.0) & BSC

EXPERIMENTAL

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.

Other: Best supportive care; Drug: Masitinib 6.0 mg/kg/day

Placebo & BSC

PLACEBO COMPARATOR

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.

Drug: Placebo; Other: Best supportive care

Interventions

Masitinib 4.5 mg/kg/day DRUG

Masitinib 4.5 mg/kg/day

Also known as: AB1010

Masitinib (4.5) & BSC

Placebo DRUG

Matching placebo

Also known as: Placebo Oral Tablet

Placebo & BSC

Best supportive care OTHER

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

Also known as: BSC

Masitinib (4.5) & BSC; Masitinib (6.0) & BSC; Placebo & BSC

Masitinib 6.0 mg/kg/day DRUG

Masitinib 6.0 mg/kg/day

Also known as: AB1010

Masitinib (6.0) & BSC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AB Science: lead

Study Sites (4)

St Charles Clinical Research

Weldon Spring, Missouri, 63304, United States

RECRUITING

Centre Hospitalier Universitaire Amiens-Picardie

Amiens, France

RECRUITING

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

Paris, France

RECRUITING

CHU Toulouse

Toulouse, France

RECRUITING

Related Publications (2)

• 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.

  PMID: 28069279 BACKGROUND

• 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.

  PMID: 36048877 DERIVED

MeSH Terms

Conditions

Mast Cell Activation Syndrome

Interventions

masitinib

Condition Hierarchy (Ancestors)

Mast Cell Activation Disorders; Immune System Diseases

Study Officials

• Julien Rossignol, MD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Study Coordinator

CONTACT

+33(0)147200014; clinical@ab-science.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Eligible patients will be randomized by means of a computerized central randomization system called IWRS (interactive web response system).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo-controlled, parallel-group, multicenter comparative study with ascending dose titrations of masitinib and matching placebo

Study Record Dates

• First Submitted: July 2, 2022
• First Posted: July 8, 2022
• Study Start: July 1, 2022
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: February 6, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3); US (1)