A phase 3 study to compare efficacy and safety of masitinib with placebo in the patients with primary progressive or secondary progressive multiple sclerosis without relapse.
- Conditions
- Patients with primary progressive or secondary progressive multiple sclerosis without relapseMedDRA version: 21.1Level: PTClassification code 10063400Term: Secondary progressive multiple sclerosisSystem Organ Class: 10029205 - Nervous system disordersMedDRA version: 21.1Level: PTClassification code 10063401Term: Primary progressive multiple sclerosisSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2021-000639-30-DE
- Lead Sponsor
- AB Science
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 800
Inclusion Criteria
Related to disease
1. Patients with either primary progressive or secondary progressive
multiple sclerosis with onset of symptoms at least five years before
baseline and with no relapse diagnosed according to the 2017 revised
McDonald’s criteria at least two years before screening
2. Patients with Expanded Disability Status Scale (EDSS) score between 3.0 to 6.0 (both inclusive) at screening and baseline
3. Patients with an EDSS score progression =1 point with no improvement during 2 years before screening
4. Absence of T1 Gadolinium-enhancing brain lesions as measured by MRI at screening
Other inclusion criteria
5. Male or female patients aged between 18 and 65 years at screening
6. Weight >45 kg and BMI between 18 and 35 kg/m2 at screening and baseline
7. Contraception, to be assessed at screening and at baseline:
Female patients 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 effective method of contraception by her male partner during the study and for 3 months and a
half after the last treatment intake
Male patients with a female partner of childbearing potential who agrees to use a highly effective method of contraception and an effective method of contraception by his female partner during the study and for 3 months and a half after the last treatment intake OR who agrees to use an effective method of contraception and a highly effective method of contraception by his female partner during the study and for 3 months and a half after the last treatment intake
Highly effective and effective methods of contraception are detailed in the
Appendix 14.1 of the protocol.
8. Patients able to understand, and willing to sign, and date the written informed consent form prior to any protocol-specific procedures, at screening. If patients are duly capable of study consent but are unable to sign by themselves due to aggravation of disease condition, written informed consent can be obtained from a legally authorized representative who can sign on behalf of the patients after confirming the patients' agreement to study participation
9. Patients able and willing to comply with study protocol and to come onsite
as per protocol visits schedule, assessed at screening and at baseline.
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 720
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80
Exclusion Criteria:
Related to disease
1. Patients suffering from a disease other than MS that would better explain the patient’s neurological clinical signs and symptoms and/or MRI lesions observed at screening
2. Inability to complete screening MRI (contraindications for MRI) and/or
any known allergy or hypersensitivity or any contra-indication to
gadolinium macrocyclic
3. Patients treated with other disease modifying treatments in the time
frames and conditions mentioned under previous treatment wash out
period, assessed at baseline
4. Patients with lymphocytes <1.0 × 109/L at screening and at baseline
Other exclusion criteria
5. Patients with hypersensitivity to masitinib or its excipients at screening
6. Patients with history (or family history) of severe skin toxicities or reactions at screening or patients taking concomitant treatment or therapies associated with severe drug-induced skin toxicity at screening and baseline
7. Patients with history of severe bone marrow disorders such as agranulocytosis or aplasia, or with abnormal laboratory results at screening and baseline defined as:
- Neutropenia with ANC <1.5 × 109/L
- Anemia with Hgb <10 g/dl
- Thrombocytopenia with platelet counts <75 × 109/L
8. Patients with history of severe hepatic disorders, such as viral hepatitis or steatohepatitis, and alcohol steatosis, or with abnormal laboratory results defined as:
- Hepatic transaminase levels >2 ULN at baseline, or
- Total bilirubin level >1.5 ULN at baseline, or
- Both hepatic transaminase levels and total bilirubin level outside of
the normal ranges at screening and baseline, or
- Albuminemia <1 × LLN at screening and baseline, or
- Patients with concomitant medication known to be associated with severe hepatotoxicity
9. Patients with pre-existing severe renal impairment, or with abnormal laboratory results at screening:
- Creatinine clearance <60 mL/min (Cockcroft and Gault formula) or
- Proteinuria >30 mg/dL (1+) on dipstick; in case of the proteinuria =1+ on the dipstick, 24 hours proteinuria must be >1.5 g/24 hours
10. Patients with current or history of severe cardiovascular disease, assessed
at screening:
- Myocardial infarction
- Unstable angina pectoris
- Coronary revascularization procedure
- Congestive heart failure of NYHA Class III or IV
- Stroke, including a transient ischemic attack
- Second degree or third-degree atrioventricular block not successfully treated with a pacemaker
- Bi-fascicular block
- QTc Fridericia interval >450 milliseconds for males and >470 milliseconds for females
- Drug induced heart failure or ischemic heart disease
- Radiotherapy induced cardiomyopathy
- Family history of unexpected death of cardiovascular origin
- Edema of cardiac origin and left ventricular ejaculation fraction =50%
11. Patients, with two or more of the risk factors listed below assessed by a cardiologist at screening as Very High Risk (calculated SCORE* =10%.) or High Risk (calculated SCORE* =5% and <10%) according to the Systematic Coronary Risk Estimation (SCORE):
- Hypertension (uncontrolled) ; - Diabetes; - Kidney disease; - Current tabagism (= 10 Pack-year: equivalent to 1 pack of 20 cigarettes for 10 years with the formula N (number of packs of 20 cigarettes smoked daily) × T (number years smoking)) Patients who stopped smoking 6 months prior to the evaluation, are not concerned.
- Hypercholesterolemia,
- Chronic obstructive pulmonary disease (COPD)
* This assessment is done according to
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy and safety of oral masitinib versus placebo in the<br>treatment of patients with primary progressive or secondary progressive multiple<br>sclerosis without relapse. ;Secondary Objective: The secondary objectives of the study are to evaluate the efficacy of masitinib compared with placebo on a range of clinical parameters of multiple sclerosis. The secondary objectives also include the assessment of safety and tolerability of masitinib as compared to placebo in terms of adverse events, vital signs, physical examination, ECG, and clinical laboratory tests. <br>;Primary end point(s): The primary endpoint is to assess the efficacy of masitinib 3.0 mg/kg/day with a dose escalation to 4.5<br>mg/kg/day after four weeks on the time to confirmed (12-weeks CDP) EDSS progression. Progression<br>is defined as 1-point worsening when EDSS score =5.5, or 0.5-point worsening if baseline score >5.5. ;Timepoint(s) of evaluation of this end point: Week 96
- Secondary Outcome Measures
Name Time Method