A Phase III, multicentre, randomized, parallel-group, double blinded, placebo controlled study to evaluate the efficacy and safety of Ocrelizumab in adults with Primary Progressive Multiple Sclerosis
Multicentre, randomized, parallel-group, double-blind, placebo controlled study. A total of 630 primary progressive MS patients will be enrolled and assigned (2:1 randomization) to either an ocrelizumab arm or a placebo arm, stratified by age and region.Total duration of the study is a minimum of 2.5 years, or until all patients have completed the study (maximum of five years).
- 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 and amp;gt;5.5.
- Brain MRI imaging, as read by a blinded, centralized reading center
Adverse events, vital signs, weight, physical and neurological examination, clinical laboratory tests, 12 lead ECG, locally reviewed MRI for safety (non MS CNS pathology), concomitant medications.
Pregnancy tests [serum/urine beta subunit human chorionic gonadotropin (beta hCG)] will be performed in women of childbearing potential.
1. Ability to provide written informed consent and to be compliant with the schedule of
2. Diagnosis of PPMS in accordance with the revised McDonald criteria (2005)
3. Ages 18-55 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,
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 their menopause 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).