A 96 weeks study to compare efficacy and safety of masitinib to placebo in the treatment of patients with primary progressiveor relapse free secondary progressive multiple sclerosis

• Register: EUCTR
• Last refreshed on: 26 November 2013
• Main ID: EUCTR2010-021219-17-PL
• Date of registration: 16/07/2013
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: A 96 weeks study to compare efficacy and safety of masitinib to placebo in the treatment of patients with primary progressiveor 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
• Date of first enrolment: 07/11/2013
• Target sample size: 450
• Recruitment status: Authorised-recruitment may be ongoing or finished
• 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: 2

Countries of recruitment

Czech Republic, France, Germany, Greece, Poland, Romania, Slovakia, Spain

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 = 2.5x ULN Bilirubin = 1.5x ULN Creatinine clearance > 60 mL/min (Cockcroft and Gault formula) Albumin = 1 x LLN Urea = 1.5 x ULN Proteinuria < 30 mg/dL on dipstick; in case of the proteinuria = 30 mg/dL, 24 hours proteinuria < 1.5g/24 hours
5. Male or female patient, aged > 18, at time of informed consent signature
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. Man and woman of childbearing 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 3 months after the last treatment intake
8. Patient able and willing to comply with study procedures as per protocol
9. 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 400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

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 active 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
PREVIOUS TREATMENT WASH OUT
12. Previous treatment with immunomodulators and/or immunosuppressors treatments including azathioprine, cladribine, cyclophosphamide, cyclosporine, methotrexate, mitoxantrone, natalizumab, mycophenolate mofetil, hematopoietic stem cell transplantation, plasma exchange or total lymphoid irradiation within 24 weeks prior to baseline
13. Interferon, glatiramer acetate, IV infusion of immunoglobulins or monthly bolus IV corticosteroids within 12 weeks prior to baseline
14. Treatment with any oral or systemic corticosteroids or adrenocorticotropic hormone (ACTH) within 4 weeks prior to baseline
15. Treatment with any investigational drug within 12 weeks prior to baseline


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

Health Condition(s) or Problem(s) studied

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

Primary progressive or relapse-free secondary progressive multiple sclerosis
MedDRA version: 16.0 Level: PT Classification code 10063401 Term: Primary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 16.0 Level: PT Classification code 10063400 Term: Secondary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

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
Other descriptive name: masitinib
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
Other descriptive name: masitinib
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)

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

Main Objective: The objective is to compare the safety and efficacy of masitinib 4.5 mg/kg/day 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) at week 96

Primary end point(s): Multiple Sclerosis Functional Composite (MSFC) at week 96

Secondary Objective: Secondary endpoints:
• Clinical assessment:
- MSFC at weeks 12, 24, 36, 48, 60, 72 and 84
- 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
- Walking speed at weeks 4, 8 and 12
- EDSS 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 a and 96
• Quality of Life assessment:MSQOL-54 at weeks 12, 24, 36, 48, 60, 72 and 84
• Quality of Life assessment: MSQOL-54 at week 96 (for the EMA)
• Use of corticosteroids for MS
• Number of hospitalizations for relapse
• Clinical and biological safety profile

Secondary Outcome(s)

Secondary end point(s): • Clinical assessment:
- MSFC at weeks 12, 24, 36, 48, 60, 72 and 84
- 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
- Walking speed at weeks 4, 8 and 12
- EDSS 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
• Quality of Life assessment:MSQOL-54 at weeks 12, 24, 36, 48, 60, 72 and 84
• Quality of Life assessment: MSQOL-54 at week 96 for Marketing Authorization in the European market
• 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, pelvic ultrasound, chest X-ray and biological parameters.

Secondary ID(s)

2010-021219-17-ES

AB07002

Source(s) of Monetary Support

AB Science