E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Smouldering Systemic or Indolent Systemic Mastocytosis with handicaps |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10026891 |
E.1.2 | Term | Mastocytosis |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective is to compare the safety and efficacy of masitinib to placebo in patients with documented Smouldering or Indolent Systemic mastocytosis with severe handicap.
Primary endpoint: - Cumulative response by patient*handicap
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E.2.2 | Secondary objectives of the trial |
- Cumulative response on pruritus among patients with the handicap at Baseline - Cumulative response on OPA score among patients with “severe” or “intolerable” handicap at Baseline - Quality of Life (QoL) : QLQ-C30 global score, functional scores and symptom scores at each visit - AFIRMM questionnaire : • global score • for each of the 52 items : cumulative response among patients with “severe” or “intolerable” handicap at Baseline - Cumulative response on micturitions among patients with the handicap at Baseline - Cumulative response on stools among patients with the handicap at Baseline - Urticaria Pigmentosa (UP) evaluation at week 12, 24 and then every 12 weeks
Safety profile of masitinib: Occurrence of Adverse Events, vital signs, EKG, Chest X-Ray, cardiac ultrasonography and biological parameters.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
As part of the international study, French patients enrolled in this study, will enter a specific cardiac surveillance in order to study potential effect of masitinib on myocardial contractibility. Echocardiogram will be performed for assessing myocardial contractibility features and especially the Left Ventricular Ejection Fraction. The objective of this sub study is to demonstrate to good cardiac safety profile of masitinib vs. placebo. |
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E.3 | Principal inclusion criteria |
1. Patient with one of the following documented mastocytosis as per WHO classification: Smouldering Systemic Mastocytosis Indolent Systemic Mastocytosis 2. Patient with documented mastocytosis and evaluable disease based upon histological criteria: typical infiltrates of mast cells in a multifocal or diffuse pattern in skin and/or bone marrow biopsy 3. Patient with documented treatment failure of his/her handicap(s) with at least one of the following therapy used at optimized dose (refer to table 2): Anti H1 Anti H2 Proton pump inhibitor Osteoclast inhibitor Cromoglycate Sodium Antileukotriene 4. Handicapped status defined as at least two of the following handicaps, including at least one among pruritus, flushes, depression and fatigue: Pruritus score ≥ 9 Number of flushes per week ≥ 8 Hamilton rating scale for depression(HAMD-17) score ≥ 19 Number of stools per day ≥ 4 Number of micturition per day ≥ 8 Fatigue Impact Scale total score (asthenia) ≥ 75 |
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E.4 | Principal exclusion criteria |
1. Patient with one of the following mastocytosis: Cutaneous Mastocytosis Not documented Smouldering Systemic Mastocytosis or Indolent Systemic Mastocytosis Systemic Mastocytosis with an Associated clonal Hematologic Non Mast cell lineage Disease (SMAHNMD) Mast cell leukaemia (MCL) Aggressive systemic mastocytosis (ASM) 2. Previous treatment with any Tyrosine Kinase Inhibitor |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary variable: Cumulative response by patient*handicap For all the patients, the response at each study visit (5 visits from week 8 to week 24) will be calculated on each handicap present at Baseline (among pruritus, flushes, Hamilton and FIS) as defined above. If data are not available for assessment at a visit because a patient left the study prematurely or had no measurement at the visit, missing data will be considered as failure (missing = failure as primary analysis). Week 4 is not considered for the calculation of this response as : -All patients take anti-histamines between Baseline and week 4 even if they didn’t take such treatment before study entry -Based on phase II studies, first month of treatment is under efficient So, from 5 to 20 responses will be calculated by patient : 5 if the patients presents only 1 handicap at Baseline corresponding to the 5 visits and 20 if the patients presents the 4 handicaps at Baseline corresponding to the 4 handicaps * the 5 visits. Sensitivity analysis: same analysis but with Last Observation Carried Forward (LOCF) then with Observed Cases (data remain missing) instead of missing = failure if data are not available for assessment at a visit because a patient left the study prematurely or had no measurement at the visit.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Overall duration of treatment |
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E.5.2 | Secondary end point(s) |
- Cumulative response on pruritus among patients with the handicap at Baseline - Cumulative response on OPA score among patients with “severe” or “intolerable” handicap at Baseline - Quality of Life (QoL) : QLQ-C30 global score, functional scores and symptom scores at each visit - AFIRMM questionnaire : • global score • for each of the 52 items : cumulative response among patients with “severe” or “intolerable” handicap at Baseline - Cumulative response on micturitions among patients with the handicap at Baseline - Cumulative response on stools among patients with the handicap at Baseline - Urticaria Pigmentosa (UP) evaluation at week 12, 24 and then every 12 weeks
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Overall duration of treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Bulgaria |
Czech Republic |
France |
Germany |
Hungary |
India |
Italy |
Latvia |
Mexico |
Poland |
Romania |
Russian Federation |
Slovakia |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of the trial is defined as last visit of the last patient at week 24.
Possible extension visits will not be taken in consideration for end of trial definition. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |