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

• Register: EUCTR
• Last refreshed on: 21 December 2021
• Main ID: EUCTR2008-000972-25-HU
• Date of registration: 16/05/2013
• Prospective Registration: Yes
• Primary sponsor: AB SCIENCE
• Public 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
• 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: 11/10/2013
• Target sample size: 200
• 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

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

Contacts

• Name: Dr. László Nagy
• Affiliation: Hungarotrial Zrt

• Name: Dr. László Nagy
• Affiliation: Hungarotrial Zrt

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
5. Patients with OPA > 2 (moderate to intolerable general handicap)
6. ECOG = 2
7. Patient with adequate organ function :
Absolute neutrophils count (ANC) = 2.0 x 109/L,
Haemoglobin = 10 g/dL
Platelets (PTL) = 100 x 109/L
AST/ALT = 3x ULN (= 5 x ULN in case of liver mast cell involvement),
Bilirubin = 1.5x ULN
Creatinine clearance >60mL/min (Cockcroft and Gault formula)
Albumin >1 x LLN
Proteinuria < 30mg/dL on the dipstick; in case of proteinuria = 1+ on dipstick, 24 hours
proteinuria should be <1.5g/24 hours
8. Male or female patient aged 18 to 75 years, weight > 50 kg, BMI between 18 and 35 kg/m²
9. Male or female patient of child bearing potential ust agree to use two methods (one for the patient
and one for the partner) of medically acceptable forms of contraception during the study and for
three months after the last treatment intake. Female patients must have a negative result in the
pregnancy tests at screening and baseline.
10. Patient must be able and willing to comply with study visits and procedures per protocol
11. Patient must understand, sign, and date the written voluntary informed consent form at the
screening visit prior to any protocol-specific procedures performed
12. Patient must understand the patient card and follow the patient card procedures in case of signs or
symptoms of severe neutropenia or severe cutaneous toxicity during the first 2 months of
treatment
13. Patient affiliated to a social security regimen
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
F.1.3 Elderly (>=65 years)
F.1.3.1 Number of subjects for this age range

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
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

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

Smouldering Systemic, Indolent Systemic or Cutaneous Mastocytosis with handicaps
MedDRA version: 16.0 Level: PT Classification code 10026891 Term: Mastocytosis System Organ Class: 10005329 - Blood and lymphatic system disorders

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 of this study is to compare the efficacy and safety of masitinib at 6 mg/kg/day to
placebo in the treatment of patients with documented Smouldering or Indolent Systemic mastocytosis
with severe handicap based on treatment effect on the pruritus score, the number of flushes per week,
the HAMD-17 score, and the Fatigue Impact Scale score.

Primary endpoint:
- Cumulative response by patient*handicap

Timepoint(s) of evaluation of this end point: 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

Primary end point(s): 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

Secondary Outcome(s)

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

Secondary end point(s): Response on at least one handicap out of 4 among pruritus, flushes, depression and fatigue
- Overall cumulative response
- Sustained response rate (two consecutive response)
- Responder rate at week 12
- Confirmed responder rate (response at week 20 then week 24)
Response on at least one handicap out of 3 among pruritus, flushes and depression/fatigue (for depression/fatigue, a patient will be considered as responder if response on both depression and fatigue as those variables are partially overlapping)
Responder rate at week 24
- Overall cumulative response
- Sustained response rate (two consecutive response)
- Responder rate at week 12
- Confirmed responder rate (response at week 20 then week 24)
Response on at least 2 handicaps out of 4 among pruritus, flushes, depression and fatigue (among patients with at least 2 handicaps at baseline)

Secondary ID(s)

2008-000972-25-FR

AB06006

Source(s) of Monetary Support

AB Science

Ethics review

Status: Approved
Approval date: 11/09/2013
Contact:

Results

• Results available: Yes
• Date Posted: 27/06/2020
• Date Completed: 02/11/2015
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-000972-25/results