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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-005406-96 | EudraCT Number |
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To evaluate the efficacy and safety of two dosing schemes of oral masitinib versus matching placebo in the treatment of patients suffering from severe MCAS with handicap unresponsive to optimal symptomatic treatment.
Multicenter, double-blind, placebo-controlled trial comparing two different dosing schemes over a 24-week treatment period.
Dosing scheme #1: Oral masitinib treatment at 3 mg/kg/day for 4 weeks, then a switch to 4.5 mg/kg/day for the remainder of the treatment period, versus placebo with a matching titration scheme. Randomization 2: 1 (Masitinib MCAS: Placebo MCAS).
Dosing scheme #2: Oral masitinib treatment at 3 mg/kg/day for 4 weeks, then a switch to 4.5 mg/kg/day for 4 weeks, then a second switch to 6 mg/kg/day for the remainder of the treatment period versus placebo treatment with a matching titration scheme. Randomization 2: 1 (Masitinib MCAS: Placebo MCAS)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Masitinib (4.5) & BSC | Experimental | Masitinib 4.5 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) for 4 weeks, given orally twice daily, with a dose escalation to 4.5 mg/kg/day for the remainder of the treatment period. Each ascending dose titration is subjected to a safety control. |
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| Masitinib (6.0) & BSC | Experimental | Masitinib 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) for 4 weeks, given orally twice daily, with a dose escalation to 4.5 mg/kg/day for4 weeks of treatment, then a second dose escalation to 6 mg/kg/day for the remainder of the treatment period. Each ascending dose titration is subjected to a safety control. |
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| Placebo & BSC | Placebo Comparator | Placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC). Participants receive a matched dose placebo, given orally twice daily. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Masitinib 4.5 mg/kg/day | Drug | Masitinib 4.5 mg/kg/day |
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| Measure | Description | Time Frame |
|---|---|---|
| Confirmed response at 50% | Confirmed response at 50%, defined as an improvement with respect to the baseline values of 50% for Pruritus, Flushes and Depression (HAMD-17 score) which should be confirmed from the previous visit. Handicaps at baseline defined as: pruritus score ≥ 9; number of flushes per week ≥ 8; HAMD-17 score ≥ 19. | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative response | Cumulative (every patient visit) response at 75% on 3 handicaps (pruritus, flush, depression) from week 8 to week 24. Analysis will be performed using Generalized Estimating Equations (GEE) model with stratification. | week 8 to week 24 |
| Confirmed response (75%) |
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Inclusion Criteria include:
Exclusion Criteria include:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Clinical Study Coordinator | Contact | +33(0)147200014 | clinical@ab-science.com |
| Name | Affiliation | Role |
|---|---|---|
| Julien Rossignol, MD | Reference Centre for Mastocytosis (CEREMAST), Necker Hospital, Paris, France | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St Charles Clinical Research | Recruiting | Weldon Spring | Missouri | 63304 | United States | |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28069279 | Background | 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 |
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No Masitinib is under clinical investigation and has not yet been approved in any sought-after indication by any health authority worldwide. As such, there is no plan for data-sharing at this point in time.
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| ID | Term |
|---|---|
| D000090267 | Mast Cell Activation Syndrome |
| ID | Term |
|---|---|
| D000090362 | Mast Cell Activation Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C526575 | masitinib |
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Randomized, double-blind, placebo-controlled, parallel-group, multicenter comparative study with ascending dose titrations of masitinib and matching placebo
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Eligible patients will be randomized by means of a computerized central randomization system called IWRS (interactive web response system).
| Placebo | Drug | Matching placebo |
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| Best supportive care | Other | Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, sodium cromoglicate, antidepressants, antileukotrienes, proton pump inhibitors, and corticosteroids. |
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| Masitinib 6.0 mg/kg/day | Drug | Masitinib 6.0 mg/kg/day |
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Confirmed response at 75%, defined as an an improvement with respect to the baseline values of 75% for Pruritus, Flushes and Depression (Hamilton Depression Rating Scale) which should be confirmed from the previous visit. The Hamilton Depression Rating Scale (HAMD-17) has 17 items and is scored between 0 and 4 points. Scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression; the maximum score being 52. |
| 24 weeks |
| Patient-Reported Outcome for Symptom Severity (PROSS) | Changes in MCAS symptom severity will also be assessed using the Patient-Reported Outcome for Symptom Severity (PROSS) questionnaire. Total and individual symptom scores will be determined at baseline and at every visit until Week 24.The PROSS questionnaire has 11 items and is scored between 0 and 10 points. A score of 0 is an absence of the symptom and a score of 10 is very severe; the maximum score being 110. | 24 weeks |
| Centre Hospitalier Universitaire Amiens-Picardie |
| Recruiting |
| Amiens |
| France |
| Necker-Enfants Malades Hospital, Centre de référence des Mastocytoses (CEREMAST) | Recruiting | Paris | France |
| CHU Toulouse | Recruiting | Toulouse | France |
| 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. |