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

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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

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.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Cumulative response (3R75%)

Secondary Outcome

 Cumulative response (4R75%)

Condition

Indolent Systemic Mastocytosis

Intervention

Masitinib

Study Arms / Comparison Groups

 Masitinib & BSC
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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

140

Start Date

July 1, 2020

Completion Date

December 2022

Primary Completion Date

December 2022

Eligibility 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.
      

Gender

All

Ages

18 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

Cristina Bulai Livideanu, MD, MSc, +33(0)147200014, [email protected]

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT04333108

Organization ID

AB15003

Secondary IDs

2016-001447-39

Responsible Party

Sponsor

Study Sponsor

AB Science


Study Sponsor

Cristina Bulai Livideanu, MD, MSc, Principal Investigator, Centre Hospitalier Universitaire, Service de Dermatologie, Toulouse -France


Verification Date

November 2020