A 96-week, prospective, multicenter, randomised, double-blind, placebo-controlled, 2-parallel groups, Phase 3 study to compare efficacy and safety of masitinib 4.5 mg/kg/day versus placebo in the treatment of patients with primary progressive or relapse-free secondary progressive multiple sclerosis

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2010-021219-17-DE
• Date of registration: 05/07/2011
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: A 96-week, prospective, multicenter, randomised, double-blind, placebo-controlled, 2-parallel groups, Phase 3 study to compare efficacy and safety of masitinib 4.5 mg/kg/day versus placebo in the treatment of patients with primary progressive or relapse-free secondary progressive multiple sclerosis
• Scientific title: A 96-week, prospective, multicenter, randomised, double-blind, placebo-controlled, 2-parallel groups, Phase 3 study to compare efficacy and safety of masitinib 4.5 mg/kg/day versus placebo in the treatment of patients with primary progressive or relapse-free secondary progressive multiple sclerosis - Not applicable
• Date of first enrolment: 31/10/2011
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-021219-17
• 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: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Bosnia and Herzegovina, Brazil, Bulgaria, France, Germany, Greece, Hungary, Italy, Mexico, Morocco, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Tunisia, Ukraine, United Kingdom, United States

Contacts

• Name: Alain Moussy
• Affiliation: AB Science

• Name: Alain Moussy
• Affiliation: AB Science

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patient suffering from either primary progressive or secondary progressive multiple sclerosis without relapse within 2 years before inclusion according to the revised McDonald’s criteria
2. Patient with EDSS score of [2.0 to 6.0] inclusive at baseline
3. Patient who had an EDSS score progression = 1 point within 2 years before inclusion
4. Patient with normal organ function defined as:
• Absolute neutrophils count (ANC) = 2 x 109/L
• Hemoglobin = 10 g/dL
• Platelets (PTL) = 100 x 109/L
• AST/ALT = 3 ULN
• Bilirubin = 1.5x ULN
• Creatinine clearance > 60 mL/min (Cockcroft and Gault formula)
• Albuminemia > 1 x LLN
• 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
5. Male or female patient aged between 18 and 75 years old, with a weight > 50 kg and BMI between 18 and 35 kg/m².
6. 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.
7. Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test), who agrees to use two highly effective methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake. Acceptable forms of contraception include:
8. Male patients must use medically acceptable methods of contraception if your female partner is pregnant, from the time of the first administration of the study drug until three months following administration of the last dose of study drug. Acceptable methods include:
9. Patient able and willing to comply with study procedures as per protocol
10. Patient able to understand, sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures

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 500
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion criteria:
1. Patient suffering from a disease other than MS that would better explain the patient’s neurological clinical signs and symptoms and/or MRI lesions
2. Patient who had a major surgery within 2 weeks of study entry
3. Patient with life expectancy < 6 months
4. Patient with history of primary malignancy < 5 years, except treated basal cell skin cancer or cervical carcinoma in situ
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 any severe and/or uncontrolled medical condition
7. Patient with a known diagnosis of human immunodeficiency virus (HIV) infection
8. Patient with known hepatitis B, hepatitis C or tuberculosis
9. Pregnant or nursing female
10. 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
11. Patient with any condition or concurrent medical events, including any clinically significant deviations from reference ranges in laboratory test, that on the opinion of the physician could be detrimental to the subjects
12. Patients requiring medication, which are prohibited in the current protocol, including corticosteroids used other than defined by the protocol, chemotherapies, immunomodulators or immunosuppressors, investigational drugs, live attenuated vaccines, drugs known to be at high risk of Stevens-Johnson syndrome.




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Primary progressive or relapse-free secondary progressive multiple sclerosis
MedDRA version: 20.1 Level: PT Classification code 10063401 Term: Primary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: PT Classification code 10063400 Term: Secondary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: mastinib
Product Code: AB1010
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: masitinb 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

Product Name: mastinib
Product Code: AB1010
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: masitinb 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)

Main Objective: The objective of the study is to compare the safety and efficacy of masitinib at 4.5 mg/kg/day or masitinib at 4.5 mg/kg/day with a dose escalation to 6 mg/kg/day after three month of treatment versus placebo in the treatment of patients with primary progressive multiple sclerosis or relapse-free secondary progressive multiple sclerosis.

Primary endpoint: Multiple Sclerosis Functional Composite (MSFC) from week 12 to week 96

Primary end point(s): Multiple Sclerosis Functional Composite (MSFC) from week 12 to week 96

Secondary Objective: Clinical assessment:
• EDSS at weeks 12, 24, 36, 48, 60, 72, 84 and 96
• Quality of Life assessment: MSQOL-54 at weeks 12, 24, 36,48, 60, 72, 84 and 96
• Timed 25-foot walk at weeks 12, 24, 36, 48, 60, 72, 84 and 96
• Nine-hole peg test, right and left hands sides (finger dexterity) at weeks 12, 24, 36, 48, 60, 72, 84 and 96
• PASAT 3 at weeks 12, 24, 36, 48, 60, 72, 84 and 96
• Modified Fatigue Impact Scale at weeks 12, 24, 36, 48, 60, 72, 84 and 96
• Hamilton Rating Scale for Depression at weeks 12, 24, 36, 48, 60, 72, 84 and 96
• Disability Impact Profile at weeks 12, 24, 36, 48, 60, 72, 84 and 96
• Health state Visual Analogue Scale (EQ-VAS) at weeks 12, 24, 36, 48, 60, 72, 84 and 96
• Use of corticosteroids for MS
• Number of hospitalizations for relapse
• Clinical and biological safety profile: occurrence of Adverse Events, potential changes in vital signs, ECG, and biological parameters.

Timepoint(s) of evaluation of this end point: week 96

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: week 12, 24, 36, 48, 60, 72, 84 and 96

Secondary end point(s): Clinical assessment:
• EDSS at weeks 12, 24, 36, 48, 60, 72, 84 and 96
• Quality of Life assessment: MSQOL-54 at weeks 12, 24, 36,48, 60, 72, 84 and 96
• Timed 25-foot walk at weeks 12, 24, 36, 48, 60, 72, 84 and 96
• Nine-hole peg test, right and left hands sides (finger dexterity) at weeks 12, 24, 36, 48, 60, 72, 84 and 96
• PASAT 3 at weeks 12, 24, 36, 48, 60, 72, 84 and 96
• Modified Fatigue Impact Scale at weeks 12, 24, 36, 48, 60, 72, 84 and 96
• Hamilton Rating Scale for Depression at weeks 12, 24, 36, 48, 60, 72, 84 and 96
• Disability Impact Profile at weeks 12, 24, 36, 48, 60, 72, 84 and 96
• Health state Visual Analogue Scale (EQ-VAS) at weeks 12, 24, 36, 48, 60, 72, 84 and 96
• Use of corticosteroids for MS
• Number of hospitalizations for relapse
• Clinical and biological safety profile: occurrence of Adverse Events, potential changes in vital signs, ECG, and biological parameters.

Secondary ID(s)

2010-021219-17-ES

AB07002

Source(s) of Monetary Support

ABScience

Ethics review

Status: Approved
Approval date:
Contact: