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
- Conditions
- Primary progressive or relapse-free secondary progressive multiple sclerosisMedDRA version: 20.1 Level: PT Classification code 10063401 Term: Primary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disordersMedDRA version: 20.0 Level: PT Classification code 10063400 Term: Secondary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2010-021219-17-SK
- Lead Sponsor
- AB Science
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 600
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, s
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.
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method