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 - ND

• Register: EUCTR
• Last refreshed on: 21 December 2021
• Main ID: EUCTR2008-000972-25-IT
• Date of registration: 17/12/2010
• Prospective Registration: No
• 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 - ND
• 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 - ND
• Date of first enrolment: 24/11/2010
• 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
• 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, Italy, Latvia, Slovakia, Spain, United Kingdom

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 ? Cutaneous 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 asthenia: ? pruritus score = 6 ? number of flushes per week = 7 ? Hamilton rating scale (depression) = 10 ? number of stools per day = 4 , ? number of mictions per day = 8 , ? Fatigue Impact Scale total score (asthenia) = 40 5. Patients with OPA > 2 (moderate to intolerable general handicap) 6. ECOG = 2 7. Patient with adequate organ function : ? absolute neutrophil count (ANC) = 2.0 x 109/L, ? platelets (PTL) = 100 x 109/L ? AST/ALT = 2.5x ULN (= 5 x ULN in case of liver mast cell involvement), ? bilirubin = 1.5x ULN ? creatinin clearance =50 mL/min (Cockrot and Gault formula) ? albumin > 0.75 x LLN ? urea = 1.5 x ULN ? proteinuria < 30mg/dL on the dipstick;; in case of proteinuria = 30 mg/dL, 24 hours proteinuria should be < 1.5g/24 hours 8. Male or female patient with age = 18 years 9. Men and women of child bearing potential (entering the study after a confirmed menstrual period and who have a negative pregnancy test) must agree to use 2 methods of medically acceptable forms of contraception during the study. Men and women of childbearing potential must agree upon using contraception for three months following their participation in the study 10. Patient should be able and willing to comply with study visits and procedures per protocol 11. Patient should understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed 12. Patient must be covered by insurance for routine costs
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: ? Systemic Mastocytosis with an Associated clonal Hematologic Non Mast cell lineage Disease (SM-AHNMD) ? Mast cell leukemia (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 condition: a. Ischemic heart disease, defined by at least one of the following condition: i. Medical history of ischemic heart disease ii. Clinical symptoms of ischemic heart disease iii. Q wave > 3 mm on the electrocardiogram iv. ST elevation or depression > 2 mm on the electrocardiogram v. Negative T wave in at least 2 leads of the electrocardiogram b. Cardiac failure, defined by at least one of the following condition: i. Medical history of cardiac failure defined by a previous left ventricular ejection fraction = 50% ii. Clinical symptoms of cardiac failure iii. NT proBNP = 300 pg/mL and/or troponin T > 0.1 ng/mL c. Conduction disorders or arrhythmia, defined by at least one of the following and confirmed by electrocardiogram: i. Severe ventricular arrhythmia (frequent premature ventricular beats) ii. Atrioventricular block at second or third level iii. Left bundle branch block 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 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, Indolent Systemic or Cutaneous mastocytosis with handicap
MedDRA version: 9.1 Level: LLT Classification code 10026891

Intervention(s)

Product Name: AB1010 Tablets
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
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: AB1010 Tablets
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
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): The primary endpoint is the percentage of responders at week 24. A patient is classified as responder if he/she presents an improvement of = 50% in at least one handicap, handicap being defined as a score above the cut in any of the 4 variables: - pruritus score = 6, - number of flushes per week = 7, - Hamilton score = 10 - Fatigue Impact Scale score = 40 Any patient with a worsening of more than 50% of any handicap, and/or with emergence of a new handicap with an increase of more than 50% from baseline, will be considered a non responder. Superiority of 6 mg/kg masitinib daily over placebo in patients suffering from mastocytosis with regard to the primary variable as given above will be tested with the following hypotheses, where ? denotes the percentage of responders at week 24: H0: ?6mg/kg masitinib bid = ?placebo bid H1: ?6mg/kg masitinib bid > ?placebo bid This means that a test for superiority will be performed in percentage of responders in the group treated with 6mg/kg/day masitinib compared to the one treated with placebo. Superiority will be tested using the Pearson Chi-square.

Secondary Objective: ? Response in at least two out of three variables among pruritus, flushes, depression or asthenia, at week 12 and week 24 ? Responder rate at week 12 ? Pruritus score at week 12 and week 24 ? Number of flushes per week at week 12 and week 24 ? Hamilton score at week 12 and week 24 ? Fatigue Impact Scale at week 12 and week 24 ? Number of mictions per day at week 12 and week 24 ? Number of stools per day at week 12 and week 24 ? QLQ-C30 scores at week 12 and week 24 ? Overall Patient Assessment (OPA) at week 12 and week 24 ? AFIRMM V2 score at week 12 and week 24 ? Percentage of patient without handicap at week 12 and 24 ? Mast cell infiltration in the skin or bone marrow at week 24 ? Serum tryptase level at week 24

Main Objective: Responder rate at week 24

Secondary ID(s)

AB06006

2008-000972-25-FR

Ethics review

Status: Approved
Approval date: 18/10/2010
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