Clinical Trials Register

Summary
EudraCT Number:	2019-001862-13
Sponsor's Protocol Code Number:	AB19001
National Competent Authority:	Ireland - HPRA
Clinical Trial Type:	EEA CTA
Trial Status:	Temporarily Halted
Date on which this record was first entered in the EudraCT database:	2020-08-04
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Ireland - HPRA

A.2

EudraCT number

2019-001862-13

A.3

Full title of the trial

A prospective, multicenter, randomised, double-blind, placebo-controlled, parallel groups, phase 3 study to compare the efficacy and safety of masitinib in combination with Riluzole versus placebo in combination with Riluzole in the treatment of patients suffering from Amyotrophic Lateral Sclerosis (ALS)

A.3.1

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

Evaluation of masitinib in Amyotrophic Lateral Sclerosis (ALS)

A.3.2

Name or abbreviated title of the trial where available

AB19001 ALS masitinib/placebo in combination with riluzole

A.4.1

Sponsor's protocol code number

AB19001

A.5.4

Other Identifiers

Name:

IND Number

Number:

120168

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/001/2020

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	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	0033147203008
B.5.5	Fax number	0033147202411
B.5.6	E-mail	vincent.arnold@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/3/16/1722
D.3 Description of the IMP
D.3.1	Product name	Masitinib 100mg
D.3.2	Product code	AB1010
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.3.9.4	EV Substance Code	AS1
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.3.11 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.IMP: 2
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/3/16/1722
D.3 Description of the IMP
D.3.1	Product name	Masitinib 200mg
D.3.2	Product code	AB1010
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.3.9.3	Other descriptive name	na
D.3.9.4	EV Substance Code	AS2
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
D.8 Placebo: 2
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

patients suffering from Amyotrophic Lateral Sclerosis (ALS)

E.1.1.1

Medical condition in easily understood language

Amyotrophic Lateral Sclerosis (ALS)

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10002026
E.1.2	Term	Amyotrophic lateral sclerosis
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to demonstrate statistically significant improvement from baseline in ALSFRS-R after 48-week treatment of two doses of masitinib versus matching placebo in patients diagnosed with ALS treated with Riluzole.

E.2.2

Secondary objectives of the trial

Secondary objectives are to assess the efficacy and safety of two doses of masitinib versus matching placebo in the treatment of patients diagnosed with ALS treated with Riluzole

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

Pharmacodynamic/biomarker(s):
Identification of pharmacodynamic biomarker(s) is needed to fully characterize the potential disease modifying effects of masitinib in ALS patients. The aim is to assess, before and during study treatment, cerebrospinal fluid (CSF) in up to 30 ALS patients and serum biomarkers in up to all randomized ALS patients known to be associated with the evolution of the disease and potentially modulated by masitinib treatment.

PharmacoGenomic (PG) study:
Determination of the genetic polymorphisms, including HLA polymorphisms that could be associated with an increased risk of masitinib-induced severe neutropenia and severe skin toxicity.

PharmacoKinetic (PK) study:
Measurement of pharmacokinetic parameters of masitinib and Riluzole in up to 10 ALS patients per group and validate population PK model for masitinib.

E.3

Principal inclusion criteria

1. Patient, male or female, diagnosed with laboratory supported probable, clinically probable or definite ALS according to the World Federation of Neurology Revised El Escorial criteria [52]
2. Patient with a familial or sporadic ALS
3. Patient aged between 18 and 75 years old inclusive at screening
4. Patient treated with a stable dose of Riluzole (100 mg/day) for at least 12 weeks prior to baseline visit
5. Patient with an ALS disease duration from diagnosis no longer than 24 months at screening
6. Patient with an ALSFRS-R total score progression between onset of the disease and screening of > 0.3 and <1.1 point/month
7. Patient with an ALSFRS-R total score decrease of ≥ 1 point between screening and baseline
8. Patient with an ALSFRS-R total score of at least 26 at screening following rules below:
- at least 3 on item #3 and
- at least 2 on each of the other 11 items (i.e. item #1, #2, #4, #5a or #5b, #6, #7, #8, #9, #10, #11 and #12)
9. Patient with an ALSFRS-R total score of at least 25 at randomization following rules below:
- at least 3 on item #3 and
- at least 2 on each of the other 11 items (i.e. item #1, #2, #4, #5a or #5b, #6, #7, #8, #9, #10, #11 and #12)
10. Contraception:
- Female patient of childbearing potential (entering the study after a menstrual period and who has a negative pregnancy test), who agrees to use a highly effective method of contraception and an effective method of contraception by her male partner during the study and for 3 months and a half after the last treatment intake
- Male patient with a female partner of childbearing potential who agrees to use a highly effective method of contraception and an effective method of contraception by his female partner during the study and for 3 months and a half after the last treatment intake OR who agrees to use an effective method of contraception and a highly effective method of contraception by his female partner during the study and for 3 months and a half after the last treatment intake
Highly effective and effective methods of contraception are detailed in appendix 15.1
11. Patient able to understand, and willing to sign, and date the written informed consent form prior to any protocol-specific procedures. If patients are duly capable of study consent but are unable to sign by themselves due to aggravation of disease condition, written informed consent can be obtained from a legally authorized representative who can sign on behalf of the patients after confirming the patients' agreement to study participation.
12. Patient able and willing to comply with study protocol and to come on-site as per protocol visits schedule
13. Patient able to understand, and willing to follow the safety procedures mentioned on the patient card in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity

E.4

Principal exclusion criteria

1. Patient with dementia or significant neurological, psychiatric, systemic or organic disease, uncontrolled or that may interfere with the conduct of the trial or its results
2. Patient with hypersensitivity to masitinib excipients
3. Patient with an FVC < 60% predicted normal value for gender, height, and age at screening
4. Patient with a weight < 41 kg and a BMI < 21 or > 30 kg/m² at screening and at baseline
5. Pregnant, or nursing female patient
6. Patient with history (or family history) of severe skin toxicities or reactions
7. Patients treated by drugs known to be at high risk for Stevens-Johnson Syndrome or for Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome
8. Patient with history of severe bone marrow disorders such as agranulocytosis or aplasia, or with abnormal laboratory results from local laboratory assessments at screening and baseline:
- Neutropenia with ANC < 1.5 x 109/L
- Anemia with Hgb < LLN and red blood cell count below the LLN
- Thrombocytopenia with platelets counts < 150 x 109/L
9. Patient with history of hepatic disorders, with a known liver disease or alcohol abuse, or with abnormal laboratory results from local laboratory assessments defined as:
- hepatic transaminase levels > 2 ULN at baseline, or
- total bilirubin level > 1.5 ULN at baseline, or
- both hepatic transaminase levels and total bilirubin level outside of the normal ranges at screening and baseline, or
- albuminemia < 1 x LLN at screening and baseline
10. Patient with pre-existing severe renal impairment, or with abnormal laboratory results from local laboratory assessments at screening and baseline:
- 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
11. Patient with active severe infection such as herpes, tuberculosis, viral hepatitis, human immunodeficiency virus infection
12. Patient with autoimmune conditions such as systemic lupus erythematosus
13. Patient with a diagnosis of cancer or evidence of continued disease within five years before screening
14. Patient with severe cardiac conditions:
- Patient with recent history of severe cardiovascular conditions including acute myocardial infarction, unstable angina pectoris, coronary revascularization procedure, congestive heart failure of NYHA Class III or IV, stroke, including a transient ischemic attack
- Patient with cardiac conduction abnormalities at study entry including a QTc Fredericia interval >450 milliseconds for males and >470 milliseconds for females, a second- or third-degree atrioventricular block not successfully treated with a pacemaker
- Patient presenting with edema of cardiac origin and left ventricular ejection fraction ≤ 50%
15. Patient with risk factors for sudden unexpected death of cardiovascular origin
16. Patient who has been exposed to an investigational treatment within 3 months prior to screening
17. Patient who has been exposed to Edaravone within at least 30 days prior to screening
18. Patient treated concomitantly with drugs known to interact with cytochrome P450 (CYP450) isoenzymes (2C9, 2D6 and 3A4)

E.5 End points

E.5.1

Primary end point(s)

Absolute Change from baseline to week 48 in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised total score

E.5.1.1

Timepoint(s) of evaluation of this end point

week 48

E.5.2

Secondary end point(s)

- Progression free survival (PFS) defined as the time from randomization to progression (decline of more than 9 points in ALSFRS-R score from baseline) or death
- Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSAQ-40) change
- Forced Vital Capacity (FVC) change
- Upper- and lower-limb muscle strength using hand-held dynamometry (HHD)
- Clinician-rated Clinical Global Impression (CGI)
- Combined Assessment of Function and Survival (CAFS)
- Overall Survival (OS)
- Event free survival (EFS) defined as the time from randomization to the first occurrence of either death or tracheostomy

Safety Analysis:
- Adverse events
- Vital signs, physical examination, ECGs
- Clinical laboratory tests (haematology, biochemistry, urinalysis and urinary cytology)

E.5.2.1

Timepoint(s) of evaluation of this end point

at W48 or event occurence (death) depending on secondary endpoint

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

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)

Yes

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

Yes

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

Argentina

Belgium

Canada

Denmark

France

Germany

Ireland

Israel

Italy

Netherlands

Poland

Portugal

Russian Federation

Slovenia

Spain

Sweden

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

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

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