Back to resultsMasitinib in Severe Indolent or Smoldering Systemic Mastocytosis Unresponsive to Optimal Symptomatic Treatment
Primary Purpose
Indolent Systemic Mastocytosis
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Masitinib
Placebo
Best Supportive Care
Sponsored by
About this trial
This is an interventional treatment trial for Indolent Systemic Mastocytosis focused on measuring 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
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- Centre Hospitalier Universitaire d'AmiensRecruiting
- Hospital Jean-MinjozRecruiting
- Grenoble University HospitalRecruiting
- Hospital Claude HuriezRecruiting
- Marseille University Hospital TimoneRecruiting
- Centre de référence de Mastocytose (CEREMAST)Recruiting
- Poitiers University HospitalRecruiting
- Centre Hospitalier UniversitaireRecruiting
- University Hospital Charité
- Erasmus University Medical CenterRecruiting
- Medical University of GdańskRecruiting
- The University Hospital in Krakow (Szpital Uniwersytecki w Krakowie)Recruiting
- University Hospital in Bucharest (Spitalul Universitar de Urgență București)Recruiting
- Almazov National Medical Research CentreRecruiting
- Dnipropetrovsk Clinical Association of Emergency Medical Care of Dnipropetrovsk RegionalRecruiting
- Private Enterprise Private Manufacturing Company AcinusRecruiting
- Guy's and St Thomas' NHS Foundation TrustRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Masitinib & BSC
Placebo & BSC
Arm Description
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.
Placebo Comparator: Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Cumulative response (4R75%)
Cumulative response in at least one of four severe baseline symptoms of mast cell mediator release (pruritus, flushes, depression, or asthenia). Response is defined as a 75% improvement from baseline for any of these four 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 20 possible responses depending on the number of severe baseline symptoms).
Cumulative response (2R75%)
Cumulative response in at least one of two severe baseline symptoms of mast cell mediator release (pruritus or flushes). Response is defined as a 75% improvement from baseline for either of these two symptoms. Cumulative response is 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 10 possible responses depending on the number of severe baseline symptoms).
Cumulative response
Cumulative response on each of the individual handicaps. Response is defined as a 75% improvement from baseline for either of these two symptoms. Cumulative response is 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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04333108
Brief Title
Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis Unresponsive to Optimal Symptomatic Treatment
Official Title
Phase 3 Study to Compare Oral Masitinib to Placebo in Treatment of Patients With Smouldering or Indolent Severe Systemic Mastocytosis, Unresponsive to Optimal Symptomatic Treatment
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2020 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
June 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AB Science
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
140 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Masitinib & BSC
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo & BSC
Arm Type
Placebo Comparator
Arm Description
Placebo Comparator:
Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)
Intervention Type
Drug
Intervention Name(s)
Masitinib
Other Intervention Name(s)
AB1010
Intervention Description
Masitinib 6 mg/kg/day
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Matching placebo
Intervention Type
Other
Intervention Name(s)
Best Supportive Care
Intervention Description
Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, proton pump inhibitors (PPI), sodium cromoglycate, antidepressants, leukotriene antagonists and corticosteroids.
Primary Outcome Measure Information:
Title
Cumulative response (3R75%)
Description
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).
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Cumulative response (4R75%)
Description
Cumulative response in at least one of four severe baseline symptoms of mast cell mediator release (pruritus, flushes, depression, or asthenia). Response is defined as a 75% improvement from baseline for any of these four 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 20 possible responses depending on the number of severe baseline symptoms).
Time Frame
24 weeks
Title
Cumulative response (2R75%)
Description
Cumulative response in at least one of two severe baseline symptoms of mast cell mediator release (pruritus or flushes). Response is defined as a 75% improvement from baseline for either of these two symptoms. Cumulative response is 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 10 possible responses depending on the number of severe baseline symptoms).
Time Frame
24 weeks
Title
Cumulative response
Description
Cumulative response on each of the individual handicaps. Response is defined as a 75% improvement from baseline for either of these two symptoms. Cumulative response is 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.
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Study Coordinator
Phone
+33(0)147200014
Email
clinical@ab-science.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cristina Bulai Livideanu, MD, MSc
Organizational Affiliation
Centre Hospitalier Universitaire, Service de Dermatologie, Toulouse -France
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Hospitalier Universitaire d'Amiens
City
Amiens
Country
France
Individual Site Status
Recruiting
Facility Name
Hospital Jean-Minjoz
City
Besançon
Country
France
Individual Site Status
Recruiting
Facility Name
Grenoble University Hospital
City
Grenoble
Country
France
Individual Site Status
Recruiting
Facility Name
Hospital Claude Huriez
City
Lille
Country
France
Individual Site Status
Recruiting
Facility Name
Marseille University Hospital Timone
City
Marseille
Country
France
Individual Site Status
Recruiting
Facility Name
Centre de référence de Mastocytose (CEREMAST)
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Name
Poitiers University Hospital
City
Poitiers
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire
City
Toulouse
Country
France
Individual Site Status
Recruiting
Facility Name
University Hospital Charité
City
Berlin
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Erasmus University Medical Center
City
Rotterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Medical University of Gdańsk
City
Gdańsk
Country
Poland
Individual Site Status
Recruiting
Facility Name
The University Hospital in Krakow (Szpital Uniwersytecki w Krakowie)
City
Kraków
Country
Poland
Individual Site Status
Recruiting
Facility Name
University Hospital in Bucharest (Spitalul Universitar de Urgență București)
City
Bucharest
Country
Romania
Individual Site Status
Recruiting
Facility Name
Almazov National Medical Research Centre
City
Saint Petersburg
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Dnipropetrovsk Clinical Association of Emergency Medical Care of Dnipropetrovsk Regional
City
Dnipropetrovs'k
Country
Ukraine
Individual Site Status
Recruiting
Facility Name
Private Enterprise Private Manufacturing Company Acinus
City
Poltava
Country
Ukraine
Individual Site Status
Recruiting
Facility Name
Guy's and St Thomas' NHS Foundation Trust
City
London
Country
United Kingdom
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
21108325
Citation
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.
Results Reference
background
PubMed Identifier
28069279
Citation
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.
Results Reference
background
PubMed Identifier
36048877
Citation
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.
Results Reference
derived
Learn more about this trial
Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis Unresponsive to Optimal Symptomatic Treatment
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