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

Indolent Systemic Mastocytosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04333108
• Other study ID #: AB15003
• Secondary ID: 2016-001447-39
• Status: Recruiting
• Phase: Phase 3
• Start date: July 1, 2020
• Est. completion date: June 2025

Study information

• Verified date: May 2023
• Source: AB Science
• Contact: Clinical Study Coordinator
• Phone: +33(0)147200014
• Email: clinical[@]ab-science.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: June 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Indolent Systemic Mastocytosis
• Mastocytosis

Intervention

Drug:
• Masitinib
Masitinib 6 mg/kg/day

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

Locations

Country	Name	City	State
France	Centre Hospitalier Universitaire d'Amiens	Amiens
France	Hospital Jean-Minjoz	Besançon
France	Grenoble University Hospital	Grenoble
France	Hospital Claude Huriez	Lille
France	Marseille University Hospital Timone	Marseille
France	Centre de référence de Mastocytose (CEREMAST)	Paris
France	Poitiers University Hospital	Poitiers
France	Centre Hospitalier Universitaire	Toulouse
Germany	University Hospital Charité	Berlin
Netherlands	Erasmus University Medical Center	Rotterdam
Poland	Medical University of Gdansk	Gdansk
Poland	The University Hospital in Krakow (Szpital Uniwersytecki w Krakowie)	Kraków
Romania	University Hospital in Bucharest (Spitalul Universitar de Urgen?a Bucure?ti)	Bucharest
Russian Federation	Almazov National Medical Research Centre	Saint Petersburg
Ukraine	Dnipropetrovsk Clinical Association of Emergency Medical Care of Dnipropetrovsk Regional	Dnipropetrovs'k
Ukraine	Private Enterprise Private Manufacturing Company Acinus	Poltava
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
AB Science

Countries where clinical trial is conducted

France,  Germany,  Netherlands,  Poland,  Romania,  Russian Federation,  Ukraine,  United Kingdom, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	24 weeks
Secondary	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).	24 weeks
Secondary	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).	24 weeks
Secondary	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.	24 weeks