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

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2008-000972-25-SK
• Date of registration: 14/12/2009
• Prospective Registration: No
• 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 Indolent with 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 III 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: 09/12/2009
• 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

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

Contacts

• Name: Clinical Project Manager
• Affiliation: Ab Science

• Name: Clinical Project Manager
• Affiliation: Ab Science

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:
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


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

Health Condition(s) or Problem(s) studied

Smouldering Systemic, 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)

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.

Timepoint(s) of evaluation of this end point: Week 24

Main Objective: The objective is to compare the safety and efficacy of masitinib to placebo in patients with indolent mastocytosis with handicap.

Primary endpoint:
- Cumulative response by patient*handicap

Secondary Objective: Secondary endpoints:
- 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
- Mastocytosis symptoms rebound effect evaluation from 1 month after
study/treatment discontinuation.

Secondary Outcome(s)

Secondary end point(s): Secondary variables
• Cumulative response on pruritus among patients with the handicap at Baseline
• OPA score
• Quality of Life (QoL) : QLQ-C30
• AFIRMM questionnaire
• Cumulative response on micturition among patients with the handicap at Baseline
• Cumulative response on stools among patients with the handicap at Baseline
• Urticaria Pigmentosa (UP) evaluation
• Mastocytosis symptoms rebound evaluation
Percentage of patients who experiencing a rebound effect on at least one
symptom after discontinuation. Mean number of symptoms showing a
rebound per discontinued patients. Percentage of patients who
experiencing a rebound effect per symptom. Mean time of the occurrence
of the rebound effect. Symptom severity will be described. Patient
overall wellbeing from treatment period will be also described.

Timepoint(s) of evaluation of this end point: Week 12 and 24. One month after treatment discontinuation for mastocytosis symptoms rebound evaluation.

Secondary ID(s)

2008-000972-25-FR

AB06006

Source(s) of Monetary Support

AB Science