Clinical Trials Register

Summary
EudraCT Number:	2008-000972-25
Sponsor's Protocol Code Number:	AB06006
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-12-14
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2008-000972-25

A.3

Full title of the trial

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

24-týždňová s možným predĺžením, prospektívna, multicentrická, randomizovaná, dvojito zaslepená, placebom kontrolovaná, s dvoma paralelnými skupinami, randomizovaná 1:1, štúdia fázy III, porovnávajúca účinnosť a bezpečnosť masitinibu v dávke 6 mg/kg/denne oproti placebu pri liečbe pacientov s klinickými prejavy tlejúcej systémovej, indolentnej systémovej alebo kožnej mastocytózy

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

Štúdia k porovnaniu účinnosti a bezpečnosti masitinibu v dávke 6 mg/kg/deň oproti placebu v liečbe pacientov s indolentnou mastocytózou s hendikepom

A.4.1

Sponsor's protocol code number

AB06006

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Ab Science
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AB Science
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Ab Science
B.5.2	Functional name of contact point	Clinical Project Manager
B.5.3	Address:
B.5.3.1	Street Address	3 avenue George V
B.5.3.2	Town/ city	Paris
B.5.3.3	Post code	75008
B.5.3.4	Country	France
B.5.4	Telephone number	33147 20 97 83
B.5.5	Fax number	33147 20 24 11
B.5.6	E-mail	igor.antonshchuk@ab-science.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/04/242
D.3 Description of the IMP
D.3.1	Product name	AB1010 Tablets
D.3.2	Product code	AB1010 Tablets
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Masitinib mesylate
D.3.9.1	CAS number	790-299-79-5
D.3.9.2	Current sponsor code	AB1010
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Masitinib mesylate
D.3.9.1	CAS number	790-299-79-5
D.3.9.2	Current sponsor code	AB1010
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Smouldering Systemic, Indolent Systemic Mastocytosis with handicaps

E.1.1.1

Medical condition in easily understood language

Indolent Mastocytosis

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	PT
E.1.2	Classification code	10026891
E.1.2	Term	Mastocytosis
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

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.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

As part of the international study, French patients enrolled in this study, will enter a specific cardiac surveillance in order to study potential effect of masitinib on myocardial contractibility. Echocardiogram will be performed for assessing myocardial contractibility features and especially the Left Ventricular Ejection Fraction. The objective of this sub study is to demonstrate to good cardiac safety profile of masitinib vs. placebo.

E.3

Principal 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

E.4

Principal 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

E.5 End points

E.5.1

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.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 24

E.5.2

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.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 12 and 24. One month after treatment discontinuation for mastocytosis symptoms rebound evaluation.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Bulgaria

Czech Republic

France

Germany

Greece

India

Italy

Latvia

Poland

Russian Federation

Slovakia

Ukraine

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

End of the trial is defined as last visit of the last patient at week 24.

Possible extension visits will not be taken in consideration for end of trial definition.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

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:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

120

F.4.2.2

In the whole clinical trial

150

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients successfully treated with masitinib will be allowed to carry on their treatment for a maximum treatment exposure of 2 years. After 2 years, patients will be allowed to continue the treatment on a case by case basis only if a documented favourable benefit/risk ratio is established by the investigator.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2009-12-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-12-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-11-02

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