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

Phase 3

Recruiting

• Conditions: Indolent Systemic Mastocytosis
• Interventions: Other: Placebo; Drug: Masitinib; Other: Best Supportive Care

• Registration Number: NCT04333108
• Lead Sponsor: 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.

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 Timeline

• Study First Submitted: 2020-04-01
• Study First Submitted QC: 2020-04-01
• Study First Posted: 2020-04-03
• Study Start: 2020-07-01
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-03
• Last Update Posted: 2023-05-06
• Primary Completion: 2024-12
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 140

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo & BSC	Best Supportive Care	Placebo Comparator: Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)
Placebo & BSC	Placebo	Placebo Comparator: Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)
Masitinib & BSC	Best Supportive Care	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.
Masitinib & BSC	Masitinib	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.

Primary Outcome Measures

Name	Time	Method
Cumulative response (3R75%)	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

Name	Time	Method
Cumulative response	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.
Cumulative response (4R75%)	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).
Cumulative response (2R75%)	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).

Trial Locations

Locations (17)

Hospital Jean-Minjoz; 🇫🇷 Besançon, France

Grenoble University Hospital; 🇫🇷 Grenoble, France

Hospital Claude Huriez; 🇫🇷 Lille, France

Centre de référence de Mastocytose (CEREMAST); 🇫🇷 Paris, France

Marseille University Hospital Timone; 🇫🇷 Marseille, France

Poitiers University Hospital; 🇫🇷 Poitiers, France

Centre Hospitalier Universitaire; 🇫🇷 Toulouse, France

University Hospital Charité; 🇩🇪 Berlin, Germany

University Hospital in Bucharest (Spitalul Universitar de Urgență București); 🇷🇴 Bucharest, Romania

Almazov National Medical Research Centre; 🇷🇺 Saint Petersburg, Russian Federation

Dnipropetrovsk Clinical Association of Emergency Medical Care of Dnipropetrovsk Regional; 🇺🇦 Dnipropetrovs'k, Ukraine

Erasmus University Medical Center; 🇳🇱 Rotterdam, Netherlands

Medical University of Gdańsk; 🇵🇱 Gdańsk, Poland

The University Hospital in Krakow (Szpital Uniwersytecki w Krakowie); 🇵🇱 Kraków, Poland

Private Enterprise Private Manufacturing Company Acinus; 🇺🇦 Poltava, Ukraine

Centre Hospitalier Universitaire d'Amiens; 🇫🇷 Amiens, France

Guy's and St Thomas' NHS Foundation Trust; 🇬🇧 London, United Kingdom