Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis Unresponsive to Optimal Symptomatic Treatment

NCT ID: NCT04333108

Last Updated: 2023-05-06

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

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

140 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-01

Study Completion Date

2025-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The purpose of this study is to evaluate the efficacy and safety of oral masitinib versus placebo in the treatment of patients suffering from smouldering or indolent systemic mastocytosis with severe symptoms of mast cell mediator release, unresponsive to optimal symptomatic treatment.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Masitinib is a selective tyrosine kinase inhibitor that modulates mast cell activity via inhibition of c-Kit, Lyn and Fyn kinase signaling pathways. This is a multicenter, randomized, double-blind, placebo-controlled, 2-parallel-group, trial comparing oral masitinib versus placebo in the treatment of patients suffering from smouldering or indolent systemic mastocytosis with severe symptoms of mast cell mediator release (also referred to as handicaps), unresponsive to optimal symptomatic treatment. The treatment period is 24 weeks. Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Indolent Systemic Mastocytosis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Masitinib & BSC

Experimental Arm:

Masitinib (titration to 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), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control.

Group Type EXPERIMENTAL

Masitinib

Intervention Type DRUG

Masitinib 6 mg/kg/day

Best Supportive Care

Intervention Type OTHER

Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, proton pump inhibitors (PPI), sodium cromoglycate, antidepressants, leukotriene antagonists and corticosteroids.

Placebo & BSC

Placebo Comparator:

Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Matching placebo

Best Supportive Care

Intervention Type OTHER

Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, proton pump inhibitors (PPI), sodium cromoglycate, antidepressants, leukotriene antagonists and corticosteroids.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Masitinib

Masitinib 6 mg/kg/day

Intervention Type DRUG

Placebo

Matching placebo

Intervention Type OTHER

Best Supportive Care

Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, proton pump inhibitors (PPI), sodium cromoglycate, antidepressants, leukotriene antagonists and corticosteroids.

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

AB1010

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Patient with one of the following documented mastocytosis subtypes (variants): Smouldering Systemic Mastocytosis, Indolent Systemic Mastocytosis
2. An excess of mast cells or a presence of abnormal mast cells in at least two organs (among skin, bone-marrow and GI Tract).
3. Patient with documented systemic mastocytosis and evaluable disease based upon histological criteria
4. Patient with documented treatment failure of his/her symptom(s) (within the past 2 years) with at least two of the symptomatic treatments used at optimized dose: Anti H1, Anti H2, Proton pump inhibitor, Antidepressants, Cromoglycate Sodium, Antileukotriene.
5. Patient with severe symptoms of mastocytosis over the 14-day run-in period including at least one among pruritus, flushes, and depression: pruritus score ≥ 9, number of flushes per week ≥ 8, Hamilton rating scale for depression (HAMD-17) score ≥ 19.

Exclusion Criteria

1. Patient with one of the following mastocytosis: Cutaneous Mastocytosis, Systemic Mastocytosis with an Associated clonal Hematologic Non Mast cell lineage Disease (SM-AHNMD), Mast cell leukemia (MCL), Aggressive systemic mastocytosis (ASM)
2. Previous treatment with any Tyrosine Kinase Inhibitor
3. Treatment with any investigational agent within 8 weeks prior to screening.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

AB Science

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Cristina Bulai Livideanu, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire, Service de Dermatologie, Toulouse -France

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Centre Hospitalier Universitaire d'Amiens

Amiens, , France

Site Status RECRUITING

Hospital Jean-Minjoz

Besançon, , France

Site Status RECRUITING

Grenoble University Hospital

Grenoble, , France

Site Status RECRUITING

Hospital Claude Huriez

Lille, , France

Site Status RECRUITING

Marseille University Hospital Timone

Marseille, , France

Site Status RECRUITING

Centre de référence de Mastocytose (CEREMAST)

Paris, , France

Site Status RECRUITING

Poitiers University Hospital

Poitiers, , France

Site Status RECRUITING

Centre Hospitalier Universitaire

Toulouse, , France

Site Status RECRUITING

University Hospital Charité

Berlin, , Germany

Site Status NOT_YET_RECRUITING

Erasmus University Medical Center

Rotterdam, , Netherlands

Site Status RECRUITING

Medical University of Gdańsk

Gdansk, , Poland

Site Status RECRUITING

The University Hospital in Krakow (Szpital Uniwersytecki w Krakowie)

Krakow, , Poland

Site Status RECRUITING

University Hospital in Bucharest (Spitalul Universitar de Urgență București)

Bucharest, , Romania

Site Status RECRUITING

Almazov National Medical Research Centre

Saint Petersburg, , Russia

Site Status RECRUITING

Dnipropetrovsk Clinical Association of Emergency Medical Care of Dnipropetrovsk Regional

Dnipro, , Ukraine

Site Status RECRUITING

Private Enterprise Private Manufacturing Company Acinus

Poltava, , Ukraine

Site Status RECRUITING

Guy's and St Thomas' NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

France Germany Netherlands Poland Romania Russia Ukraine United Kingdom

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Clinical Study Coordinator

Role: CONTACT

+33(0)147200014

References

Explore related publications, articles, or registry entries linked to this study.

Paul C, Sans B, Suarez F, Casassus P, Barete S, Lanternier F, Grandpeix-Guyodo C, Dubreuil P, Palmerini F, Mansfield CD, Gineste P, Moussy A, Hermine O, Lortholary O. Masitinib for the treatment of systemic and cutaneous mastocytosis with handicap: a phase 2a study. Am J Hematol. 2010 Dec;85(12):921-5. doi: 10.1002/ajh.21894.

Reference Type BACKGROUND
PMID: 21108325 (View on PubMed)

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

Review additional registry numbers or institutional identifiers associated with this trial.

2016-001447-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AB15003

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.