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

May 3, 2023 updated by: AB Science

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / 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 Type

Interventional

Enrollment (Anticipated)

140

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Amiens, France
        • Recruiting
        • Centre Hospitalier Universitaire d'Amiens
      • Besançon, France
        • Recruiting
        • Hospital Jean-Minjoz
      • Grenoble, France
        • Recruiting
        • Grenoble University Hospital
      • Lille, France
        • Recruiting
        • Hospital Claude Huriez
      • Marseille, France
        • Recruiting
        • Marseille University Hospital Timone
      • Paris, France
        • Recruiting
        • Centre de référence de Mastocytose (CEREMAST)
      • Poitiers, France
        • Recruiting
        • Poitiers University Hospital
      • Toulouse, France
        • Recruiting
        • Centre Hospitalier Universitaire
  • Germany
      • Berlin, Germany
        • Not yet recruiting
        • University Hospital Charité
  • Netherlands
      • Rotterdam, Netherlands
        • Recruiting
        • Erasmus University Medical Center
  • Poland
      • Gdańsk, Poland
        • Recruiting
        • Medical University of Gdansk
      • Kraków, Poland
        • Recruiting
        • The University Hospital in Krakow (Szpital Uniwersytecki w Krakowie)
  • Romania
      • Bucharest, Romania
        • Recruiting
        • University Hospital in Bucharest (Spitalul Universitar de Urgență București)
  • Russian Federation
      • Saint Petersburg, Russian Federation
        • Recruiting
        • Almazov National Medical Research Centre
  • Ukraine
      • Dnipropetrovs'k, Ukraine
        • Recruiting
        • Dnipropetrovsk Clinical Association of Emergency Medical Care of Dnipropetrovsk Regional
      • Poltava, Ukraine
        • Recruiting
        • Private Enterprise Private Manufacturing Company Acinus
  • United Kingdom
      • London, United Kingdom
        • Recruiting
        • Guy's and St Thomas' NHS Foundation Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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 Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
24 weeks
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).
24 weeks
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.
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AB Science

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2020

Primary Completion (Anticipated)

December 1, 2024

Study Completion (Anticipated)

June 1, 2025

Study Registration Dates

First Submitted

April 1, 2020

First Submitted That Met QC Criteria

April 1, 2020

First Posted (Actual)

April 3, 2020

Study Record Updates

Last Update Posted (Estimate)

May 4, 2023

Last Update Submitted That Met QC Criteria

May 3, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AB15003
  • 2016-001447-39 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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