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

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ClinicalTrials.gov Identifier: NCT04333108
Recruitment Status : Recruiting
First Posted : April 3, 2020
Last Update Posted : November 30, 2021
Sponsor:
Information provided by (Responsible Party):
AB Science

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.

Condition or disease Intervention/treatment Phase
Indolent Systemic Mastocytosis Drug: Masitinib Other: Placebo Other: Best Supportive Care Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: 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
Actual Study Start Date : July 1, 2020
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.

Drug: Masitinib
Masitinib 6 mg/kg/day
Other Name: AB1010

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

Placebo Comparator: Placebo & BSC

Placebo Comparator:

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

Other: Placebo
Matching placebo

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




Primary Outcome Measures :
  1. Cumulative response (3R75%) [ Time Frame: 24 weeks ]
    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 :
  1. Cumulative response (4R75%) [ Time Frame: 24 weeks ]
    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).

  2. Cumulative response (2R75%) [ Time Frame: 24 weeks ]
    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).

  3. Cumulative response [ Time Frame: 24 weeks ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04333108


Contacts
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Contact: Clinical Study Coordinator +33(0)147200014 clinical@ab-science.com

Locations
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United States, Minnesota
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States, 55905
United States, New York
The Trustees of Columbia University Not yet recruiting
New York, New York, United States, 10027
France
Centre Hospitalier Universitaire d'Amiens Recruiting
Amiens, France
Grenoble University Hospital Recruiting
Grenoble, France
Centre de référence de Mastocytose (CEREMAST) Not yet recruiting
Paris, France
Centre Hospitalier Universitaire Recruiting
Toulouse, France
Germany
University Hospital Charité Not yet recruiting
Berlin, Germany
Sponsors and Collaborators
AB Science
Investigators
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Principal Investigator: Cristina Bulai Livideanu, MD, MSc Centre Hospitalier Universitaire, Service de Dermatologie, Toulouse -France
Publications:
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Responsible Party: AB Science
ClinicalTrials.gov Identifier: NCT04333108    
Other Study ID Numbers: AB15003
2016-001447-39 ( EudraCT Number )
First Posted: April 3, 2020    Key Record Dates
Last Update Posted: November 30, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AB Science:
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
Additional relevant MeSH terms:
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Mastocytosis
Mastocytosis, Systemic
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Skin Diseases
Immune Complex Diseases
Hypersensitivity
Immune System Diseases