Study to compare efficacy and safety of masitinib at 6 mg/kg/day to placebo in treatment of patients with Systemic mastocytosis with severe handicap

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2008-000972-25-ES
• Date of registration: 03/10/2014
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: Study to compare efficacy and safety of masitinib at 6 mg/kg/day to placebo in treatment of patients with Systemic mastocytosis with severe handicap
• Scientific title: A 24-week with possible extension, prospective, multicentre, randomized, double blind, placebo-controlled, 2-parallel group with a randomization 1:1, Phase 3 study to compare efficacy and safety of masitinib at 6 mg/kg/day to placebo in treatment of patients with Smouldering Systemic, Indolent Systemic or Cutaneous Mastocytosis with handicap.
• Date of first enrolment: 03/02/2015
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-000972-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Bulgaria, Czech Republic, France, Germany, Greece, Hungary, India, Italy, Latvia, Mexico, Poland, Romania, Russian Federation, Slovakia, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Consuelo Pozo
• Affiliation: ALPHA BIORESEARCH

• Name: Consuelo Pozo
• Affiliation: ALPHA BIORESEARCH

Key inclusion & exclusion criteria

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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 130
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
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 (SM-AHNMD)
? Mast cell leukaemia (MCL)
? Aggressive systemic mastocytosis (ASM)
2. Previous treatment with any Tyrosine Kinase Inhibitor
3. Patient presenting with cardiac disorders defined by at least one of the following conditions:
? Patient with recent cardiac history (within 6 months) of:
- Acute coronary syndrome
- Acute heart failure (class III or IV of the NYHA classification)
- Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
? Patient with cardiac failure class III or IV of the NYHA classification
? Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
? Syncope without known aetiology within 3 months
? Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension
4. Patient who had major surgery within 2 weeks prior to screening visit
5. Vulnerable population defined as:
? Life expectancy < 6 months
? Patient with < 5 years free of malignancy, except treated basal cell skin cancer or cervical carcinoma in situ
? Patient with any severe and/or uncontrolled medical condition
? Patient with known diagnosis of human immunodeficiency virus (HIV) infection
6. Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent, or institutionalized by court decision
7. Patient with any condition that the physician judges could be detrimental to subjects participating in this study; including any clinically important deviations from normal clinical laboratory values or concurrent medical events
Previous treatment
8. Change in the symptomatic treatment of mastocytosis or administration of any new treatment of mastocytosis within 4 weeks prior to baseline
9. Treatment with any investigational agent within 4 weeks prior to baseline



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Smouldering Systemic or Indolent Systemic Mastocytosis with handicaps
MedDRA version: 17.1 Level: PT Classification code 10026891 Term: Mastocytosis System Organ Class: 10005329 - Blood and lymphatic system disorders

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: AB1010 Tablets
Product Code: AB1010 Tablets
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: Masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: 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

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.

Secondary Objective: - 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.

Timepoint(s) of evaluation of this end point: Overall duration of treatment

Secondary Outcome(s)

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

Timepoint(s) of evaluation of this end point: treatment period: 24 weeks

Secondary ID(s)

2008-000972-25-FR

AB06006

Source(s) of Monetary Support

AB Science

Ethics review

Status: Approved
Approval date:
Contact: