Relapsing multiple sclerosis MedDRA version: 16.1 Level: PT Classification code 10048393 Term: Multiple sclerosis relapse System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Merck KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: "For inclusion in the trial, all of the following inclusion criteria must be fulfilled: A. Signed Informed Consent 1. Written informed consent obtained prior to the initiation of any protocol-required procedures. B. Target Population 2. Diagnosis of MS as defined by McDonald criteria of 2010 3. At least 1 documented relapse during the previous year OR at least 2 documented relapses during the previous 2 years prior to Randomization 4. EDSS (Expanded Disability Status Score) of 0 to 5.5, inclusive 5. Clinically stable, with no relapse within 30 days prior to Randomization C. Age and Reproductive Status 6. Male or female subjects 18 to 55 years of age 7. Women of childbearing potential (WOCBP) must use 2 adequate forms of contraception to avoid pregnancy throughout the trial (such as a double barrier method) and for up to 8 weeks after the last dose of IMP in such a manner that the risk of pregnancy is minimized NOTE: WOCBP includes any female who has experienced menarche and who has not undergone successful sterilization (such as hysterectomy, bilateral tubal ligation, bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea > 12 consecutive months, or women on hormone replacement therapy with documented serum follicle stimulating hormone [FSH] level > 35 mIU/mL). Women using oral, implanted, or injectable contraceptive hormones or using mechanical products (such as an intrauterine device, diaphragm, condoms, etc) to prevent pregnancy; or practicing abstinence; or where the partner is sterile (such as with a vasectomy), must be considered to be of childbearing potential. 8. WOCBP must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [hCG]) at the time of Screening AND a negative urine (dipstick) pregnancy test at the time of Randomization 9. Women must not be breastfeeding 10. Males must be surgically sterilized or agree to the use of a double-barrier method for the duration of the trial and must agree to refrain from sperm donation for the duration of the trial " 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 1176 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: "A. Medical History and Concurrent Diseases 1. Neuromyelitis optica, clinically isolated syndrome, primary or secondary (without relapses) progressive multiple sclerosis 2. Chronic disease of the immune system other than MS or a known immunodeficiency syndrome 3. Malignancy 4. Macular edema or uveitis 5. Corneal herpes 6. Inability to undergo slit lamp and OCT assessment 7. Inability to complete an MRI or contraindications for MRI 8. History of sudden cardiac arrest 9. Ischemic cardiac disease including myocardial infarction, stable angina pectoris, unstable angina pectoris 10. Congestive heart failure New York Heart Association Class III or Class IV 11. Uncontrolled hypertension 12. Severe untreated sleep apnea 13. Cerebrovascular disease in the 6 months prior to Randomization 14. Symptomatic bradycardia or recurrent syncope 15. Mobitz Type II second degree or high-grade AV block 16. Sinoatrial heart block or sick sinus syndrome 17. Resting HR of 450 msec for male subjects and > 470 msec for female subjects on 12-lead ECG 38. Left bundle branch block 39. Right bundle branch block with fascicular block (left or right) or any ECG with RBBB and first degree AV block (PR interval > 240 msec) or RBBB with a QRS duration > 140 msec 40. Intraventricular conduction defect with a QRS duration > 140 msec Laboratory exclusions: 41. ALT or AST > 2 x ULN at Screening 42. Serum creatinine > 1.5 mg/dL at Screening 43. Total bilirubin > 1.5 x ULN (except for Gilber
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to demonstrate the effect of ONO 4641 versus IFN ß 1a (Avonex) 30 µg on the proportion of subjects, with RMS, who remain qualifying relapse–free during their participation in the trial when the last evaluable subject completes 1 year. ;Secondary Objective: "To demonstrate the effect of ONO 4641 versus: -IFN-ß-1a (Avonex) 30 µg on qualifying ARR in subjects with RMS treated over 2 years -IFN ß 1a (30 µg) on the number of new or enlarging T2 lesions over 1 and 2 years -IFN ß 1a (30 µg) on disability progression over 2 years and disability improvement over 2 years Other Secondary Objectives are to demonstrate the effect of ONO 4641 on: -additional clinical relapse outcomes (e.g., proportion relapse-free at 2 years) and MRI parameters (e.g., brain atrophy) in subjects with RMS -disease-activity-free (DAF) status in subjects with RMS -Symbol Digit Modalities Test (SDMT) and Paced Auditory Serial Addition Test (PASAT) as measures of cognitive function in subjects with RMS To demonstrate the safety and tolerability of treatment with ONO 4641 in RMS subjects";Primary end point(s): "Proportion of subjects free of qualifying relapse over at least 1 year (48 weeks). Relapses confirmed by the Adjudication Committee to meet the definition of qualifying relapse will contribute to the analysis for the primary endpoint." ;Timepoint(s) of evaluation of this end point: 1 year | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): "• The qualifying Annual Relapse Rate over 2 years • Number of new or enlarging hyperintense lesions on T2 weighted MRI over 1 and 2 years • Time to 3-month confirmed disability progression over 2 years • Time to 3-month confirmed disability improvement over 2 years • Time to 6-month confirmed disability progression and improvement over 2 years • Change from Baseline on the MSFC Z-score at 2 years • Proportion of subjects relapse-free over 2 years • Number and volume of new or persisting T1 Gd-enhancing lesions • T2 lesion volume • Number of combined unique active MRI lesions • Proportion of subjects with no new T1 Gd-enhancing lesions • Proportion of subjects with no new or enlarging T2 lesions • Number of new T1 hypointense lesions • Percent change in brain volume • Proportion of T1 Gd-enhancing lesions evolving into new persistent black holes • Proportion of subjects DAF (Disease Activity Free) (DAF status is defined as a subject having no qualifying relapse, no 3-month sustained change in EDSS, or no active lesions as assessed by MRI [new T1 Gd-enhancing lesions, or new/enlarging T2 lesions]) • Change from Baseline in SDMT and PASAT scores • Safety and tolerability of ONO 4641 " ;Timepoint(s) of evaluation of this end point: 1 and 2 years | — |
Countries
Argentina, Belarus, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Czech Republic, Denmark, Finland, France, Georgia, Germany, Greece, Hungary, Israel, Italy, Mexico, Netherlands, New Zealand, Peru, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Turkey, Ukraine, United Arab Emirates, United Kingdom, United States
Contacts
Public ContactCommunication Centre merck KGaA
Merck KGaA
Outcome results
None listed