Prospective, multicentre, randomised, open-label, active-controlled, parallel groups, phase 2b/3 study to compare efficacy and safety of masitinib at 3 mg/kg/day with switch to 4.5 then 6 mg/kg/day as single agent first line treatment.
Conditions
Interventions
Product Name: mastinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: masitinib mesylate
CAS Number:
Sponsors
AB Science
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient with documented relapsing-remitting multiple sclerosis (RR-MS) according to revised McDonald’s criteria including MRI scan revealing lesion consistent with the diagnosis of MS. 2. Patient with unsatisfactory response to first line treatment defined as : a. Under treatment with interferon beta-1a, interferon beta-1b, peginterferon beta-1a or glatiramer acetate for at least 12 months before randomisation; b. With at least one relapse during the 12-months before randomisation or at least 2 relapses during the 24-months before randomisation, under treatment. Relapse is defined as a new or a worsening of an existing neurological sign lasting more than 24 hours in patients who have been stable, were improving or slowly progressing and in whom there was no infection, fever or withdrawal of steroid. c. Taking the same treatment during 3 months prior randomisation 3. Patient with EDSS score in the range of 0 to 5.0 at the baseline visit. 4. Patient with adequate organ function 5. Male or female patient, aged 18 to 75 years, weight = 41 kg, BMI between 18 and 35 kg/m². 6. 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. 7. 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 8. Patient able and willing to comply with study procedures as per protocol. 9. Patient able to understand, and willing to sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures. 10. 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 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
Exclusion criteria: 1. Patients with primary progressive, secondary progressive or progressive relapsing multiple sclerosis. 2. Patient suffering from a disease other than MS that would better explain the patient’s neurological clinical signs and symptoms and/or MRI lesions. 3. Patient with MS relapse occurred within 50 days prior to randomisation and patients with previous relapse not stabilized at the time of the screening. 4. Patient treated with natalizumab, fingolimod, teriflunomide or dimethyl fumarate. 5. Patient treated within 12 weeks prior to randomisation with an approved disease modifying therapy other than interferon beta-1a, interferon beta-1b, peginterferon beta-1a, glatiramer acetate (azathioprine, cladribine, cyclophosphamide, cyclosporine, methotrexate, plasmapheresis, micophenolate mofetyl, cytapheresis,...). 6. Known allergy to gadolinium-DTPA and/or any contraindication to MRI examination. 7. Patient who previously received mitoxantrone. 8. Patient who previously received treatment with anti-lymphocyte, anti-lymphocyte monoclonal antibody (e.g. alemtuzumab) or total lymphoid irradiation. 9. Patient who had a major surgery within 4 weeks of study entry. 10. 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. 11. Patient with life expectancy < 12 months. 12. History of primary malignancy < 5 years, except treated basal cell skin cancer or cervical carcinoma in situ. 13. Patient with a severe and/or uncontrolled medical condition according to judgment of the investigator. 14. Pregnant or lactating female patient. 15. 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. 16. Patient with a known diagnosis of human immunodeficiency virus (HIV) infection or with CD4 < 200/mm3. 17. Patient with known hepatitis B, hepatitis C or tuberculosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: week 96;Secondary Objective: not applicable;Primary end point(s): Annualised relapse rate defined as the number of confirmed relapse per year;Main Objective: The objective of the study is to compare the efficacy and/or safety of masitinib at 3 mg/kg/day with switch to 4.5 then to 6 mg/kg/day to interferon beta-1a, interferon beta-1b, peginterferon beta-1a or glatiramer acetate in patients with relapsing remitting multiple sclerosis with unsatisfactory response to these first line treatments | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: week 4,8,12,16,20,24, 36, 48, 60, 75, 84 and 96; Secondary end point(s): • Response assessment: - EDSS Cumulative probability of sustained disability progression at week 12, 24, 48, 72 and 96 in EDSS EDSS score at week 12, 24, 48, 72 and 96 - Relapse Relapse rate per patient at week 12, 24, 48, 72 and 96 Use of corticosteroids for Multiple Sclerosis Severity of relapse and number of hospitalization for potential relapse • MRI endpoints: - T1 gadolinium-enhancing lesions at week 48 and 96 - T2 hyperintense lesions at week 48 and 96 - T1 hypointense lesions at week 48 and 96 - Atrophy: measure of brain parenchymal fraction (BPF) at week 48 and 96 - MRI criteria from ASL (Arterial Spi Labelling) : cerebral blood flow (CBF) in ml/100 g/min, cerebral blood volume (CBV) in ml/100 g and mean transit time (MTT) in seconds, at baseline, week 48 and 96 (optional) • Multiple Sclerosis Functional Composite (MSFC) at week 12, 24, 48, 72 and 96 • Quality of life assessment: - MSQOL-54 at week 12, 24, 48, 72 and 96 - EQ-Visual Analogue Scale for Quality of life at week 12, 24, 48, 72 and 96 - Beck Depression Inventory at week 12, 24, 48, 72 and 96 - Modified Fatigue Impact Scale at week 12, 24, 48, 72 and 96 • Safety profile Clinical and biological safety profile: occurrence of Adverse Events, potential changes in vital signs, ECG, chest X-ray and biological parameters | — |
Countries
Argentina, Belgium, Brazil, Bulgaria, Canada, Colombia, Germany, Greece, Italy, Mexico, Slovakia, Spain, Switzerland, United Kingdom
Contacts
Public ContactAlain Moussy
AB Science
Outcome results
None listed