E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Progressive Multiple Sclerosis (PPMS) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063401 |
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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 |
To investigate the efficacy of ocrelizumab compared with placebo in patients with primary progressive multiple sclerosis, as measured by the time to onset of sustained disability progression over the treatment period, defined as anincrease in EDSS that is sustained for at least 12 weeks, based on regularly scheduled visits. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of ocrelizumab compared with placebo, as reflected bythe following: • Time to sustained disability progression over the treatment period, defined as an increase in EDSS that is sustained for at least 24 weeks • Change in timed 25-foot walk from baseline to Week 120 • Change in total volume of T2 lesions on MRI scans of the brain from baseline to week 120 • To evaluate the safety and tolerability of ocrelizumab in patients with primary progressive multiple sclerosis as compared with placebo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Ability to provide written informed consent and to be compliant with the schedule of protocol assessments; 2. Diagnosis of PPMS in accordance with the revised McDonald criteria (2005); 3. Ages 18-50 years inclusive; 4. EDSS at screening from 3.0 to 6.5 points; 5. Score of ≥ 2.0 on the Functional Systems (FS) scale for the pyramidal system that is due to lower extremity findings; 6. Disease duration from the onset of MS symptoms: a. less than 15 years in patients with an EDSS at screening > 5.0 b. less than 10 years in patients with an EDSS at screening ≤ 5.0; 7. Documented history or presence at screening of at least one of the following laboratory findings in a CSF specimen [source documentation of laboratory results and method must be verified]: a. elevated IgG index b. one or more IgG oligoclonal bands detected by isoelectric focusing 8. For sexually active female and male patients of reproductive potential, use of reliable means of contraception as described below as a minimum (adherence to local requirements, if more stringent, is required*): • Two methods of contraception throughout the trial, including the active treatment phase AND for 48 weeks after the last dose of ocrelizumab, or until their B-cells have repleted, whichever is longer. Acceptable methods of contraception include one primary (e.g. systemic hormonal contraception or tubal ligation of the female partner, vasectomy of the male partner) AND one secondary barrier method (e.g. latex condoms, spermicide) OR a double barrier method (e.g. latex condom, intrauterine device, vaginal ring or pessary plus spermicide (e.g. foam, vaginal suppository, gel, cream)); 9. For patients of non reproductive potential (adherence to local requirements,if more stringent, is required*): • Women may be enrolled if postmenopausal (i.e. spontaneous amenorrhea for the past year confirmed by an FSH level greater than 40 mIU/mL) unless the patient is receiving a hormonal therapy for theirmenopause or surgically sterile (i.e. hysterectomy, complete bilateral oophorectomy); • Men may be enrolled if they are surgically sterile (castration). * Based on local Ethics Committees or National Competent Authority feedback additional requirements to assure contraception or to confirm menopause may be required (e.g. serum estradiol compatible with post-menopause status, longer duration of amenorrhea, higher level of FSH). |
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E.4 | Principal exclusion criteria |
Patients who meet the following criteria will be excluded from study entry: 1. History of relapsing remitting multiple sclerosis, secondary progressive, or progressive relapsing multiple sclerosis at screening; 2. Inability to complete an MRI (contraindications for MRI include but are not restricted to known allergy to gadolinium contrast dyes, renal impairment which would contraindicate gadolinium injection, claustrophobia, weight ≥ 140 kg, pacemaker, cochlear implants, intracranial vascular clips, surgery within 6 weeks of entry into the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI, etc.); 3. Contraindications for or intolerance to oral or i.v. corticosteroids, including methylprednisolone administered i.v., according to the country label, including: a. Psychosis not yet controlled by a treatment; b. Hypersensitivity to any of the constituents; 4. Known presence of other neurologic disorders, including but not limited to, the following: a. History of ischemic cerebrovascular disorders (e.g. stroke, transient ischemic attack) or ischemia of the spinal cord; b. History or known presence of CNS or spinal cord tumor (e.g. meningioma, glioma); c. History or known presence of potential metabolic causes of myelopathy (e.g. untreated vitamin B12 deficiency); d. History or known presence of infectious causes of myelopathy (e.g. syphilis, Lyme disease, HTLV-1, herpes zoster myelopathy); e. History of genetically inherited progressive CNS degenerative disorder (e.g. hereditary paraparesis; MELAS [mitochondrial myopathy, encephalopathy, lactic acidosis, stroke] syndrome); f. Neuromyelitis optica; g. History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., lupus, antiphospholipid antibody syndrome, Sj�gren’s syndrome, Beh�et’s disease); h. History or known presence of sarcoidosis; i. History of severe, clinically significant brain or spinal cord trauma (e.g., cerebral contusion, spinal cord compression); j. History of PML. Et al... |
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E.5 End points |
E.5.1 | Primary end point(s) |
Disability progression defined as an increase of ≥ 1.0 point from the baseline EDSS (Expanded Disability Status Scale) score (not attributable to another etiology) if baseline EDSS≤5.5; increase of ≥0.5 point from the baseline EDSS score if baseline EDSS >5.5. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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.8.3 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 105 |
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 |
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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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La fine dello studio e` definita come la data in cui verra` ricevuto l’ultimo dato da parte dell’ultimo paziente. |
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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 | 5 |
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 | 5 |
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 |