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: 22 May 2017
• Main ID: EUCTR2008-000972-25-GR
• Date of registration: 01/07/2014
• 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: 19/01/2015
• 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: Igor ANTONSHCHUK
• Affiliation: AB Science

• Name: Igor ANTONSHCHUK
• 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
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. Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test), who agrees to use two highly effective methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake.
10. Male patients must use medically acceptable methods of contraception if your female partner is pregnant, from the time of the first administration of the study drug until three months following administration of the last dose of study drug.
Male patients must use two highly effective methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake.
11. Patient must be able and willing to comply with study visits and procedures per protocol
12. Patient must understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed
13. 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

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) yes
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

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 handicap.
MedDRA version: 17.0 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: masitinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Other descriptive name: n/a
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: masitinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Other descriptive name: n/a
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): • 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).

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.

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

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: As described above

Secondary ID(s)

2008-000972-25-FR

AB06006

Source(s) of Monetary Support

AB Science