Clinical Trials Register

Summary
EudraCT Number:	2010-020992-21
Sponsor's Protocol Code Number:	AB06012
National Competent Authority:	Greece - EOF
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-12-06
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

Greece - EOF

A.2

EudraCT number

2010-020992-21

A.3

Full title of the trial

A 24-week with possible extension, prospective, multicenter, randomised, double-blind, controlled, 3-parallel groups, phase 2b/3 study to compare efficacy and safety of masitinib at 3 and 4,5 mg/kg/day to methotrexate, with a randomisation 1:1:1, in treatment of patients with active rheumatoid arthritis with inadequate response to 1. methotrexate or to 2. any DMARD including at least one biologic drug if patients previously failed methotrexate or to 3. methotrexate in combination with any DMARD including biologic drugs

Mία ελεγχόμενη, τυχαιοποιημένη, διπλά-τυφλή, προοπτική, πολυκεντρική μελέτη 3 παραλλήλων θεραπευτικών σχημάτων, φάσης ΙΙb/ΙΙΙ, διάρκειας 24 εβδομάδων με πιθανότητα επέκτασης για τη σύγκριση της αποτελεσματικότητας και της ασφάλειας της μασιτινίμπης σε δόση 3 και 4,5 mg/kg/ημέρα με τη μεθοτρεξάτη, με τυχαιοποίηση 1:1:1, στη θεραπεία ασθενών με ενεργό ρευματοειδή αρθρίτιδα με ανεπαρκή ανταπόκριση 1. στην μεθοτρεξάτη ή 2. σε οποιοδήποτε ανοσοτροποποιητικό αντιρρευματικό φάρμακο (DMARD), συμπεριλαμβανομένου ενός τουλάχιστον βιολογικού φαρμάκου, εάν οι ασθενείς έχουν προηγουμένως αποτύχει στη θεραπεία με μεθοτρεξάτη ή 3. στη μεθοτρεξάτη σε συνδυασμό με οποιοδήποτε DMARD, συμπεριλαμβανομένων και των βιολογικών φαρμάκων

A.3.1

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

Comparison of efficacy of masitinib versus methotrexate in the treatment of rheumatoid arthritis

A.3.2

Name or abbreviated title of the trial where available

AB1010 in treatement of patients with active rheumatoide arthritis.

A.4.1

Sponsor's protocol code number

AB06012

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	Cécile VISSAC-SABATIER
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	0033147 20 77 50
B.5.5	Fax number	0033147 20 24 11
B.5.6	E-mail	cecile.vissac@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	Masitinib
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	not applicable
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.3.9.3	Other descriptive name	not applicable
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Methotrexate
D.2.1.1.2	Name of the Marketing Authorisation holder	Orion Corporation
D.2.1.2	Country which granted the Marketing Authorisation	France
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	Methotrexate
D.3.2	Product code	not applicable
D.3.4	Pharmaceutical form	Capsule, hard
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	METHOTREXATE
D.3.9.1	CAS number	59-05-2
D.3.9.2	Current sponsor code	not applicable
D.3.9.3	Other descriptive name	not applicable
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	2,5 mg
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	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	Capsule, hard
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

Rheumatoid Arthritis

E.1.1.1

Medical condition in easily understood language

Arthritis

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.1
E.1.2	Level	PT
E.1.2	Classification code	10039073
E.1.2	Term	Rheumatoid arthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue 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

ACR20 at week 24

E.2.2

Secondary objectives of the trial

• Response assessment:
• ACR20 at week 12
• ACR at week 12 and 24:
• ACR50,
• ACR70,
• ACR 90,
• ACRn
• Time to first response according to ACR20 and ACR50
• DAS28 at week 12 and 24:
• DAS28 (disease activity score)
• DAS28 < 2.6 (complete remission),
• DAS28 < 3.2 (low disease activity),
• CRP and ESR level at week 12 and 24
• CRP and ESR values
• Percentage of patients with an improvement of CRP and ESR >50%, between 25 and 50%, between 0 and 25% or no improvement
• Quality of life assessment:
• Visual assessment scale at week 12 and 24 of:
• pain
• asthenia
• general health
• Quality of life assessed of SF36 at week 12 and 24
• Health Assessment Questionnaire (HAQ) score and at week 12 and 24
• Hamilton score at week 12 and 24
• Fatigue Impact scale at week 12 and 24
• Safety assessments: Adverse events, vital signs, laboratory data.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient with rheumatoid arthritis diagnosed according to American College of Rheumatology (ACR) criteria for at least 6 months.
2. Patient with ACR functional class I-III
3. Patient who have active RA consisting of
• ≥ 6 swollen joints (over 66 swollen joints)
• ≥ 6 tender joints (over 68 tender joints)
• and at least 2 out of 3 of the following:
1. erythrocyte sedimentation rate (ESR/first hour) ≥ 20 mm
2. C-reactive protein (CRP) ≥ 10 mg/L
3. morning stiffness ≥ 45 minutes at both screening and baseline.
4. Patient who failed (defined as active RA with stable dose during 3 months) methotrexate or any DMARD including biologics drugs if patients previously failed methotrexate or methotrexate in combination with any DMARD including biologics drugs (Biologic drugs being defined as any of the following therapies: anti-TNFα, Anti-CD20, Anti-IL1, Anti-IL6, CTLA4)
5. Patient with a disease onset at > 16 years of age
6. Patient with an adequate organ function:
• Absolute neutrophils count (ANC) ≥ 2 x 109/L
• White blood cells count ≥ 4 x 109/L
• Haemoglobin ≥ 10 g/dL
• Platelets (PTL) ≥ 100 x 109/L
• AST/ALT ≤ 2.5x ULN
• Bilirubin ≤ 1.5x ULN
• Gamma GT ≤ 2.5 x ULN
• Creatinine clearance ≥ 50 mL/min (Cockcroft and Gault formula)
• Albumin > 1 x LLN
• Urea ≤ 1.5 x ULN
• Proteinuria < 30 mg/dL on the dipstick; in case of proteinuria ≥ 30 mg/dL, 24 hours proteinuria < 1.5g/24 hours
7. Male or female patient, age >18 years, weighing more than 49.9 kg and with a Body Mass Index (BMI) <35
8. Patient able to understand the patient card and to follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity, during the first 2 months of treatment
9. Male or female patient of child bearing potential, (entering the study after a menstrual period and who have a negative pregnancy test) must agree to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 6 months after the last treatment intake
10. Patient able and willing to comply with study visits and procedures per protocol
11. Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures being performed.

E.4

Principal exclusion criteria

1. Patient from whom the use of methotrexate is contraindicated as per its SPC (i.e. patient with severe renal or liver failure, patient with pre-existing blood dyscrasia, patient with alcohol abuse, patient with acute or chronic infection, patient with methotrexate intolerance, patient being treated with live attenuated vaccine)
2. Patient with documented fibromyalgia
3. Patient who have had a major surgery within 2 weeks prior to study entry
4. Patient with lactose intolerance
5. Patient presenting with cardiac disorders defined by at least one of the following conditions:
• Patient with recent cardiac history (within 6 months) of:
• Acute coronary syndrome
• Acute heart failure (class III or IV of the NYHA classification)
• Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
• Patient with cardiac failure class III or IV of the NYHA classification
• Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
• Syncope without known aetiology within 3 months
• Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension
6. Patient with life expectancy < 6 months
7. Patient with history of primary malignancy < 5 years; except treated basal cell skin cancer or cervical carcinoma in situ
8. Patient with a severe and/or uncontrolled medical condition
9. Pregnant or lactating woman
10. Patient diagnosed with human immunodeficiency virus (HIV) infection
11. 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.
12. Patient who were treated with methotrexate >20 mg cannot be included in the study
Previous treatments:
13. Administration of a DMARD (except methotrexate) within 4 weeks (or 5 half-lives, whichever is longer) prior to screening except for leflunomide which requires a specific wash-out period of 2 weeks before screening and infliximab which requires a wash-out period of 8 weeks.
14. Administration of more than one Non Steroidal Anti-Inflammatory Drug (NSAID) or change of dose of NSAID within 4 weeks of screening or NSAID use greater than the maximum recommended dose.
15. Administration of more than 10 mg/day of prednisone or equivalent or change in the dose of prednisone or equivalent, or having intra-articular corticosteroid injection or bolus intramuscular or intravenous treatment with corticosteroids (>20 mg prednisone or equivalent) within 4 weeks of screening.
16. Treatment with any investigational agent within 4 weeks of screening.

E.5 End points

E.5.1

Primary end point(s)

Percentage of responders at week 24, a responder being defined as patient with ACR20 at week 24

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 24

E.5.2

Secondary end point(s)

Response assessment:
• ACR20 at week 12
• ACR at week 12 and 24:
• ACR50,
• ACR70,
• ACR 90,
• ACRn
• Time to first response according to ACR20 and ACR50
• DAS28 at week 12 and 24:
• DAS28 (disease activity score)
• DAS28 < 2.6 (complete remission),
• DAS28 < 3.2 (low disease activity),
• CRP and ESR level at week 12 and 24
• CRP and ESR values
• Percentage of patients with an improvement of CRP and ESR >50%, between 25 and 50%, between 0 and 25% or no improvement
• Quality of life assessment:
• Visual assessment scale at week 12 and 24 of:
• pain
• asthenia
• general health
• Quality of life assessed of SF36 at week 12 and 24
• Health Assessment Questionnaire (HAQ) score and at week 12 and 24
• Hamilton score at week 12 and 24
• Fatigue Impact scale at week 12 and 24
• Safety assessments: Adverse events, vital signs, laboratory data.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 12 and 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)

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

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

Czech Republic

Germany

India

Monaco

Poland

Romania

Slovakia

Spain

Thailand

Turkey

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

After 24 weeks on treatment, in case there is a clinical benefit, the patients can stay in the study a continue receiving the drug

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

Number of subjects for this age range:

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:

300

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

150

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

250

F.4.2.2

In the whole clinical trial

450

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)

NOT DIFFERENT

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

2012-12-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-11-20

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2017-03-10

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials