Clinical Trials Register

Summary
EudraCT Number:	2021-005406-96
Sponsor's Protocol Code Number:	AB2006
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2024-09-26
Trial 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

France - ANSM

A.2

EudraCT number

2021-005406-96

A.3

Full title of the trial

A 24-week, multicenter, randomized, double blind, placebo-controlled, dose-range finding phase II study to compare efficacy and safety of oral masitinib to placebo in treatment of patients with severe mast cell activation syndrome (MCAS) with handicap unresponsive to optimal symptomatic treatment

A.3.1

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

A 24-week study to compare efficacy and safety of oral masitinib to placebo in the treatment of patients with severe mast cell activation syndrome (MCAS) with handicap unresponsive to optimal symptomatic treatment

A.4.1

Sponsor's protocol code number

AB2006

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	Chief Executive Officer
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	33147202311
B.5.5	Fax number	33147202411
B.5.6	E-mail	a.moussy@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	No
D.2.5.1	Orphan drug designation number
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	790299-79-5
D.3.9.2	Current sponsor code	AB1010
D.3.9.3	Other descriptive name	Masitinib mesylate
D.3.9.4	EV Substance Code	SUB32266
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	790299-79-5
D.3.9.3	Other descriptive name	Masitinib mesylate
D.3.9.4	EV Substance Code	SUB32266
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

severe mast cell activation syndrome (MCAS) with handicap unresponsive to optimal symptomatic treatment

E.1.1.1

Medical condition in easily understood language

severe mast cell activation syndrome (MCAS)

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10075217
E.1.2	Term	Mast cell activation syndrome
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 primary objective is to evaluate the masitinib treatment will show a significant trend on response at
50% on 3 handicaps (pruritus, flush, depression) at week 24.

E.2.2

Secondary objectives of the trial

The secondary objectives of the study are to evaluate the efficacy of masitinib compared with placebo
efficacy on the cumulative response on handicaps, reducing symptom severity and quality of life. The
secondary objectives also include the assessment of safety and tolerability of masitinib as compared to
placebo in terms of adverse events, vital signs, physical examination, ECG, and clinical laboratory tests.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient with Mast cell activation syndrome (MCAS)
For diagnosis of MCAS, the patients must fulfill the following criteria:
a) Clinical Criteria:
Episodic occurrence of typical MC-related clinical symptoms (urticaria, angioedema, flushing,
pruritus, nausea, hoarseness, vomiting, diarrhea, abdominal cramping, hypotensive syncope,
tachycardia, wheezing, conjunctival injection, nasal congestion, and headache) affecting 2 or
more organ systems.
b) Biomarker Criteria:
Increase in serum total tryptase by at least 20% above baseline plus 2 ng/ml during or within 4 h
after a symptomatic period.
Or
Documented evidence of above-normal levels for one of the following MC mediators according
to local laboratory criteria:
• Random serum tryptase, prostaglandin D2, histamine;
• Random urinary histamine, N-methylhistamine, prostaglandin D2, and its metabolite 11F2 alpha;
• 24-hour urinary histamine, N-methylhistamine, prostaglandin D2, and its metabolite 11F2 alpha.
2. Patient with documented treatment failures of his/her handicap(s) (within last two years) with at least two of the symptomatic treatments used at an optimized dose (Minimal duration of each treatment should be at least 8 weeks):
• Anti-H1
• Anti-H2
• Corticosteroids
• Antidepressants
• Cromoglycate Sodium
• Antileukotriene
3. Patients must be on a stable dose of Anti-H1 for a minimum of 4 weeks before screening and should remain at a stable dose throughout the study period. For other symptomatic treatments, if the patient takes Corticosteroids, Anti-H2 or PPI or Antidepressants or Cromoglycate Sodium or
Antileukotriene, the treatment must have started at least 4 weeks before Screening and must be stable throughout the study.
4. Age between 18 to 75 years (inclusive).
5. Weight > 45 kg and BMI between 18 and 35 kg/m2

E.4

Principal exclusion criteria

1. Previous treatment with any Tyrosine Kinase Inhibitor.
2. Any change in the symptomatic treatment of SM, including the systemic corticosteroids, or
administration of any new treatment for SM within 4 weeks prior to screening.
3. Treatment with any investigational agent within 8 weeks prior to screening.
4. Patients with current or history of severe cardiovascular disease.
• Myocardial infarction
• Unstable angina pectoris
• Coronary revascularization procedure
• Congestive heart failure of NYHA Class III or IV
• Stroke, including a transient ischemic attack
• Second degree or third-degree atrioventricular block not successfully treated with a pacemaker
• Bi-fascicular block
• QTc Fridericia interval > 450 milliseconds for males and > 470 milliseconds for females
• Drug-induced heart failure or ischemic heart disease
• Radiotherapy induced cardiomyopathy
• Family history of an unexpected death of cardiovascular origin.
5. Patients with two or more of the risk factors listed below assessed by a cardiologist as Very High Risk (calculated SCORE ≥10%.) or High Risk calculated SCORE ≥5% and <10%) according to the
Systematic Coronary Risk Estimation (SCORE):
• Hypertension (uncontrolled)
• Diabetes
• Kidney disease,
• Current tabagism (≥ 10 Pack-year: equivalent to 1 pack of 20 cigarettes per 10 years with the
formula N (number of packs of 20 cigarettes smoked daily) x T (number years smoking)). Patients who stopped smoking 6 months prior to evaluation are not concerned.
• Hypercholesterolemia
• COPD
This assessment is done according to the Systematic Coronary Risk Estimation (SCORE) using the
country-specific free full version of HeartScore°, the interactive tool for predicting and managing the
risk of heart attack and stroke in Europe, available at https://www.heartscore.org/en_GB/access. If
a country-specific version is not available, an EU one should be used.
6. Patient who had major surgery within 2 weeks prior to the screening visit.
7. Known hypersensitivity to masitinib or to any of its excipients
8. Patient with concomitant treatment or therapies associated with severe drug-induced skin toxicity.
9. Female patients who are pregnant or are breastfeeding.
10. Patient with following laboratory results out of the ranges detailed below at screening:
• Absolute neutrophils count (ANC) ≤ 1.5 x 109/L
• Haemoglobin ≤ 10 g/dL
• Platelets (PLT) ≤ 100 x 109/L
• Albuminemia ≤ 1 x LLN
11. Patient with history of hepatic disorders, recent alcohol abuse or recent history of hepatic impairment defined as hepatic transaminase levels >1.5 x ULN or total bilirubin level > 1 x ULN
12. Patient with severe pre-existing renal impairment, or with abnormal laboratory results from local
laboratory assessments at screening:
• Creatinine clearance < 60 mL/min (Cockcroft and Gault formula)
• Proteinuria > 30 mg/dL (1+) on dipstick; in case of the proteinuria ≥ 1+ on the dipstick, 24 hours
proteinuria must be > 1.5g/24 hours
13. Patients treated concomitantly with strong inducers of CYP3A4, substrates of CYP3A4 with a
narrow therapeutic index, or inhibitors of CYP2C8.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is confirmed response at 50% at week 24 using stratified Cochran Mantel-
Haenszel (CMH) test on 3 handicap scores (pruritus, flush, depression).

E.5.1.1

Timepoint(s) of evaluation of this end point

W24

E.5.2

Secondary end point(s)

The secondary endpoints of the study are:
• Cumulative and every four weeks (every patient’s visit) response at 75% on 3 handicaps (pruritus, flush, depression) from week 8 to week 24.
• Confirmed response (CR) at 75% at week 24
• Cumulative and every four weeks (every patient’s visit) response on 4 handicaps (pruritus,
flushes, depression, fatigue by FSS) from week 8 to week 24.
• Cumulative and every four weeks (every patient’s visit) response on 4 handicaps (pruritus, flush,
depression, fatigue by FIS) from week 8 to week 24.
• Cumulative and every four weeks (every patient’s visit) response on 2 handicaps (pruritus, flush)
from week 8 to week 24.
• Cumulative and every four weeks (every patient’s visit) response on each of the individual
handicaps from week 8 to week 24: Pruritus, Flushes, Depression, Fatigue by FSS.
• Confirmed response (CR) at week 24: Pruritus, Flushes, Depression, Fatigue by FSS.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 8 to Week 24

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

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

France

Hungary

Ireland

Italy

Lithuania

Netherlands

Norway

Poland

Portugal

Slovenia

Spain

Sweden

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

LVLS

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

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:

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

F.4.2.2

In the whole clinical trial

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)

None

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

2022-01-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-02-08

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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