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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-001447-39 | EudraCT Number |
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Masitinib & BSC | Experimental | 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. |
|
| Placebo & BSC | Placebo Comparator | Placebo Comparator: Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Masitinib | Drug | Masitinib 6 mg/kg/day |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Clinical Study Coordinator | Contact | +33(0)147200014 | clinical@ab-science.com |
| Name | Affiliation | Role |
|---|---|---|
| Cristina Bulai Livideanu, MD, MSc | Centre Hospitalier Universitaire, Service de Dermatologie, Toulouse -France | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre Hospitalier Universitaire d'Amiens | Recruiting | Amiens | France | |||
| Hospital Jean-Minjoz |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21108325 | Background | 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. | |
| 28069279 |
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| Placebo | Other | Matching placebo |
|
| Best Supportive Care | Other | Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, proton pump inhibitors (PPI), sodium cromoglycate, antidepressants, leukotriene antagonists and corticosteroids. |
|
| 24 weeks |
| 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 |
| 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 |
| Recruiting |
| Besançon |
| France |
| Grenoble University Hospital | Recruiting | Grenoble | France |
| Hospital Claude Huriez | Recruiting | Lille | France |
| Marseille University Hospital Timone | Recruiting | Marseille | France |
| Centre de référence de Mastocytose (CEREMAST) | Recruiting | Paris | France |
| Poitiers University Hospital | Recruiting | Poitiers | France |
| Centre Hospitalier Universitaire | Recruiting | Toulouse | France |
| University Hospital Charité | Not yet recruiting | Berlin | Germany |
| Erasmus University Medical Center | Recruiting | Rotterdam | Netherlands |
| Medical University of Gdańsk | Recruiting | Gdansk | Poland |
| The University Hospital in Krakow (Szpital Uniwersytecki w Krakowie) | Recruiting | Krakow | Poland |
| University Hospital in Bucharest (Spitalul Universitar de Urgență București) | Recruiting | Bucharest | Romania |
| Almazov National Medical Research Centre | Recruiting | Saint Petersburg | Russia |
| Dnipropetrovsk Clinical Association of Emergency Medical Care of Dnipropetrovsk Regional | Recruiting | Dnipro | Ukraine |
| Private Enterprise Private Manufacturing Company Acinus | Recruiting | Poltava | Ukraine |
| Guy's and St Thomas' NHS Foundation Trust | Recruiting | London | United Kingdom |
| 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. |
| 36048877 | Derived | Latham BD, Oskin DS, Crouch RD, Vergne MJ, Jackson KD. Cytochromes P450 2C8 and 3A Catalyze the Metabolic Activation of the Tyrosine Kinase Inhibitor Masitinib. Chem Res Toxicol. 2022 Sep 19;35(9):1467-1481. doi: 10.1021/acs.chemrestox.2c00057. Epub 2022 Sep 1. |
| ID | Term |
|---|---|
| D034721 | Mastocytosis, Systemic |
| D008415 | Mastocytosis |
| D011537 | Pruritus |
| D001821 | Blushing |
| D016116 | Piebaldism |
| ID | Term |
|---|---|
| D009372 | Neoplasms, Connective Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D000090362 | Mast Cell Activation Disorders |
| D007154 | Immune System Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012877 | Skin Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009633 | Nonverbal Communication |
| D003142 | Communication |
| D001519 | Behavior |
| D000417 | Albinism |
| D015785 | Eye Diseases, Hereditary |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D000592 | Amino Acid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D012873 | Skin Diseases, Genetic |
| D017496 | Hypopigmentation |
| D010859 | Pigmentation Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C526575 | masitinib |
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