E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary progressive or relapse-free secondary progressive multiple sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
Primary progressive or relapse-free secondary progressive multiple sclerosis |
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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 | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063401 |
E.1.2 | Term | Primary progressive multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063400 |
E.1.2 | Term | Secondary progressive multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective is to compare the efficacy and safety 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: EDSS : Absolute change from baseline considering all measurements from W12 to W96
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E.2.2 | Secondary objectives of the trial |
Secondary endpoints: • Quality of Life assessment: MSQOL-54 from week 12 to week 96 • 100%-improvement of Multiple Sclerosis Functional Composite (MSFC) score from week 12 to week 96 • Timed 25-foot walk from week 12 to week 96 • Nine-hole peg test, right and left hands sides (finger dexterity) from week 12 to week 96 • PASAT 3 from week 12 to week 96 • Modified Fatigue Impact Scale from week 12 to week 96 • Hamilton Rating Scale for Depression from week 12 to week 96 • Disability Impact Profile from week 12 to week 96 • Health state Visual Analogue Scale (EQ-VAS) from week 12 to week 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, chest X-ray and biological parameters.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 and 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 • Negative urinary cytology 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. 7. 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 acceptable method of contraception by her male partner during the study and for 3 months 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 acceptable method of contraception by his female partner during the study and for 3 months after the last treatment intake OR who agrees to use an acceptable method of contraception and a highly effective method of contraception by his female partner during the study and for 3 months after the last treatment intake. Highly effective methods of contraception include: a. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal b. Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable c. Intrauterine device (IUD) d. Intrauterine hormone-releasing system (IUS) e. Bilateral tubal occlusion f. Vasectomized male (azoospermia assessed medically) g. Sexual abstinence (Its reliability should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient) ▪ Acceptable methods of contraception include: a. Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action b. Male or female condom with or without spermicide c. Cap, diaphragm or sponge with spermicide 8. Female patient of childbearing potential must have a negative pregnancy test at screening and baseline 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
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E.4 | Principal 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 history of primary malignancy < 5 years, except treated basal cell skin cancer or cervical carcinoma in situ 4. 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 5. Patient with any severe and/or uncontrolled medical condition 6. Patient with a known diagnosis of human immunodeficiency virus (HIV) infection 7. Patient with known hepatitis B, hepatitis C or tuberculosis 8. Pregnant or nursing female 9. 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 10. 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 11. 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
EDSS : Absolute change from baseline considering all measurements from W12 to W96 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary endpoints: • Quality of Life assessment: MSQOL-54 from week 12 to week 96 • 100%-improvement of Multiple Sclerosis Functional Composite (MSFC) score from week 12 to week 96 • Timed 25-foot walk from week 12 to week 96 • Nine-hole peg test, right and left hands sides (finger dexterity) from week 12 to week 96 • PASAT 3 from week 12 to week 96 • Modified Fatigue Impact Scale from week 12 to week 96 • Hamilton Rating Scale for Depression from week 12 to week 96 • Disability Impact Profile from week 12 to week 96 • Health state Visual Analogue Scale (EQ-VAS) from week 12 to week 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, chest X-ray and biological parameters.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 98 |
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 | Information not present in EudraCT |
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 |
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 |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |