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

NCT04333108 | Unknown Phase 3 DMC FDA Drug

• 2 other identifiers: AB150032016-001447-39
• Study Type: interventional
• Target: 140
• Locations: 8 countries
• Sites: 17

Brief Summary

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.

Conditions

Indolent Systemic Mastocytosis

Keywords

Mastocytosis with handicap; Mastocytosis; Mast cell; Mast cell infiltration; Skin; Bone marrow; Pruritus; Flushes; c-kit; c-kit mutation; Wild Type; Mutation Asp-816-Val(D816V); Indolent systemic mastocytosis; smoldering systemic mastocytosis

Outcome Measures

Primary Outcomes (1)

• Cumulative response (3R75%)

  Cumulative response in at least one of three severe baseline symptoms of mast cell mediator release (pruritus, flushes, or depression). Response was defined as a 75% improvement from baseline for any of these three symptoms. Cumulative response was defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period (ie, with five scheduled visits, each patient had a maximum of five to 15 possible responses depending on the number of severe baseline symptoms).

  24 weeks

Secondary Outcomes (3)

• Cumulative response (4R75%)

  24 weeks

• Cumulative response (2R75%)

  24 weeks

• Cumulative response

  24 weeks

Study Arms (2)

Masitinib & BSC

EXPERIMENTAL

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.

Drug: Masitinib; Other: Best Supportive Care

Placebo & BSC

PLACEBO COMPARATOR

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

Other: Placebo; Other: Best Supportive Care

Interventions

Masitinib DRUG

Masitinib 6 mg/kg/day

Also known as: AB1010

Masitinib & BSC

Placebo OTHER

Matching placebo

Placebo & BSC

Best Supportive Care OTHER

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

Masitinib & BSC; Placebo & 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 one of the following documented mastocytosis subtypes (variants): Smouldering Systemic Mastocytosis, Indolent Systemic Mastocytosis
• An excess of mast cells or a presence of abnormal mast cells in at least two organs (among skin, bone-marrow and GI Tract).
• Patient with documented systemic mastocytosis and evaluable disease based upon histological criteria
• 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.
• 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.

You may not qualify if:

• 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)
• Previous treatment with any Tyrosine Kinase Inhibitor
• Treatment with any investigational agent within 8 weeks prior to screening.

Sponsors & Collaborators

• AB Science: lead

Study Sites (17)

Centre Hospitalier Universitaire d'Amiens

Amiens, France

RECRUITING

Hospital Jean-Minjoz

Besançon, France

RECRUITING

Grenoble University Hospital

Grenoble, France

RECRUITING

Hospital Claude Huriez

Lille, France

RECRUITING

Marseille University Hospital Timone

Marseille, France

RECRUITING

Centre de référence de Mastocytose (CEREMAST)

Paris, France

RECRUITING

Poitiers University Hospital

Poitiers, France

RECRUITING

Centre Hospitalier Universitaire

Toulouse, France

RECRUITING

University Hospital Charité

Berlin, Germany

NOT YET RECRUITING

Erasmus University Medical Center

Rotterdam, Netherlands

RECRUITING

Medical University of Gdańsk

Gdansk, Poland

RECRUITING

The University Hospital in Krakow (Szpital Uniwersytecki w Krakowie)

Krakow, Poland

RECRUITING

University Hospital in Bucharest (Spitalul Universitar de Urgență București)

Bucharest, Romania

RECRUITING

Almazov National Medical Research Centre

Saint Petersburg, Russia

RECRUITING

Dnipropetrovsk Clinical Association of Emergency Medical Care of Dnipropetrovsk Regional

Dnipro, Ukraine

RECRUITING

Private Enterprise Private Manufacturing Company Acinus

Poltava, Ukraine

RECRUITING

Guy's and St Thomas' NHS Foundation Trust

London, United Kingdom

RECRUITING

Related Publications (3)

• 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.

  PMID: 21108325 BACKGROUND

• 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

Mastocytosis, Systemic; Mastocytosis; Pruritus; Blushing; Piebaldism

Interventions

masitinib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Mast Cell Activation Disorders; Immune System Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Nonverbal Communication; Communication; Behavior; Albinism; Eye Diseases, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Skin Diseases, Genetic; Hypopigmentation; Pigmentation Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Cristina Bulai Livideanu, MD, MSc

  Centre Hospitalier Universitaire, Service de Dermatologie, Toulouse -France

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Study Coordinator

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2020
• First Posted: April 3, 2020
• Study Start: July 1, 2020
• Primary Completion: December 1, 2024
• Study Completion: June 1, 2025
• Last Updated: May 6, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); NL (1); RU (1); GB (1); PL (2); RO (1); FR (8); UA (2)