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

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2010-021219-17-SK
• Date of registration: 06/07/2011
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public 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
• 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: 01/02/2012
• Target sample size: 600
• Recruitment status: Not Recruiting
• 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: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

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 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
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.

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

Primary progressive or relapse-free secondary progressive multiple sclerosis
MedDRA version: 20.1 Level: PT Classification code 10063401 Term: Primary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: PT Classification code 10063400 Term: Secondary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

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

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
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

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
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)

Main Objective: The objective of the study is to compare the efficacy and safety of masitinib at 4.5 mg/kg/day or masitinib at 4.5 mg/kg/day with a dose escalation to 6 mg/kg/day after three month of treatment versus placebo in the treatment of patients with primary progressive multiple sclerosis or relapse-free secondary progressive multiple sclerosis.
The efficacy analysis will be performed after the randomized patients have undergone 96 weeks of treatment.
Primary endpoint:
- EDSS : Absolute change from baseline considering all measurements from W12 to W96

Primary end point(s): EDSS : Absolute change from baseline considering all measurements from W12 to W96

Secondary Objective: 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.

Timepoint(s) of evaluation of this end point: from week 12 to week 96

Secondary Outcome(s)

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.

Timepoint(s) of evaluation of this end point: from week 12 to week 96

Secondary ID(s)

AB07002

2010-021219-17-ES

Source(s) of Monetary Support

AB Science

Ethics review

Status: Approved
Approval date:
Contact: