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

• Register: EUCTR
• Last refreshed on: 1 February 2020
• Main ID: EUCTR2008-000972-25-LV
• Date of registration: 07/06/2010
• 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 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: 13/08/2010
• 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; 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, Slovakia, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Project Director
• Affiliation: AB Science

• Name: Clinical Project Director
• 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
- 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:
- 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
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 13
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

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


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: 13.1 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)

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:
? Responder rate at week 24

Primary end point(s): Primary variable: Responder rate
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

Secondary Objective: Secondary endpoints:
? 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
Safety profile of masitinib: Occurrence of Adverse Events, vital signs, EKG, Chest X-Ray, cardiac ultrasonography and biological parameters.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 12 and 24

Secondary end point(s): - 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 rating scale for depression score at week 12 and week 24
- Fatigue Impact Scale at week 12 and week 24
- Number of micturitions 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

Secondary ID(s)

2008-000972-25-FR

AB06006

Source(s) of Monetary Support

AB Science

Ethics review

Status: Approved
Approval date: 10/06/2010
Contact: