A Study of Ocrelizumab in Patients With Primary Progressive Multiple Sclerosis

• Register: EUCTR
• Last refreshed on: 11 March 2020
• Main ID: EUCTR2010-020338-25-BE
• Date of registration: 22/09/2010
• Prospective Registration: Yes
• Primary sponsor: F.Hoffmann-La Roche
• Public title: A Study of Ocrelizumab in Patients With Primary Progressive Multiple Sclerosis
• Scientific title: A Phase III, multicenter, randomized, parallel-group, double blinded, placebo controlled study to evaluate the efficacy and safety of ocrelizumab in adults with Primary Progressive Multiple Sclerosis - Oratorio
• Date of first enrolment: 26/05/2011
• Target sample size: 630
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020338-25
• 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: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Israel, Italy, Lithuania, Mexico, Netherlands, New Zealand, Norway, Peru, Poland, Portugal, Russian Federation, Slovakia, Spain, Switzerland, Ukraine, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
• Adult patients, 18-55 years of age
• Primary Progressive Multiple Sclerosis (according to revised McDonald criteria)
• Expanded Disability Status Scale (EDSS) 3.0 to 6.5 points
• Disease duration from onset of MS symptoms < 15 years if EDSS > 5.0, < 10 years if EDSS = 5.0
• Sexually active male and female patients of reproductive potential must use two methods of contraception throughout the study treatment phase and for 48 weeks for females and 24 weeks for males after the last dose

Patients who meet the following entry criteria may participate in the OLE phase:
• Completed the Blinded Treatment Period of the trial and who, in the opinion of the Investigator, may benefit from treatment with ocrelizumab;
• Able and willing to provide written informed consent to participate in the OLE phase and to comply with the study protocol;
• Willing to continue to use at least two contraceptive methods
• Meet the re-treatment criteria with ocrelizumab
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 630
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• History of relapsing remitting multiple sclerosis, secondary progressive, or progressive relapsing multiple sclerosis at screening
• Contraindications for Magnetic Resonance Imaging (MRI)
• Known presence of other neurologic disorders
• Known active infection or history of or presence of recurrent or chronic infection
• History of cancer, including solid tumors and hematological malignancies (except for basal cell, in situ squamous cell carcinomas of the skin and in situ carcinoma of the cervix that have been excised and resolved)
• Previous treatment with B-cell targeted therapies (e.g. rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab)
• Any previous treatment with lymphocyte trafficking blockers, with alemtuzumab, anti-CD4, cladribine, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation
• Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study;


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Primary Progressive Multiple Sclerosis (PPMS)
MedDRA version: 21.1 Level: PT Classification code 10063401 Term: Primary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

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

Intervention(s)

Product Name: ocrelizumab 300mg/10ml
Product Code: Ro 496-4913/F07
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ocrelizumab
CAS Number: 637334-45-3
Current Sponsor code: RO4964913
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Ocrevus
Product Name: ocrelizumab 300mg/10ml
Product Code: Ro 496-4913/F07
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ocrelizumab
CAS Number: 637334-45-3
Current Sponsor code: RO4964913
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Up to 11 years

Main Objective: To investigate the efficacy of ocrelizumab compared with placebo in patients with primary progressive multiple sclerosis, as measured by the time to onset of confirmed disability progression over the treatment period, defined as an increase in EDSS that is sustained for at least 12 weeks, based on regularly scheduled visits.

Primary end point(s): 1. Efficacy: Time to onset of confirmed disability progression, defined as an increase in Expanded Disability Status Scale (EDSS) score that is sustained for at least 12 weeks

Secondary Objective: To evaluate the efficacy of ocrelizumab compared with placebo, as reflected by the following:
• The time to onset of confirmed disability progression over the treatment period, defined as an increase in EDSS that is sustained for at least 24 weeks
• The change in 25-foot timed walk from baseline to Week 120
• The change in total volume of T2 lesions on MRI scans of the brain from baseline to week 120
• The percentage change in total brain volume as detected by brain MRI from Week 24 to Week 120
• The change in SF-36 Health Survey version 2 (SF-36v2) Physical Component Summary (PCS) score from baseline to Week 120
• To evaluate the safety and tolerability of ocrelizumab 300 mg × 2 (over 24-week treatment cycles) compared with placebo in patients with PPMS

Secondary Outcome(s)

Secondary end point(s): 1. Time to confirmed disability progression, defined as an increase in EDSS score that is sustained for at least 24 weeks
2. Change in timed 25-foot walk
3. Change in total volume of T2 lesions on magnetic resonance imaging (MRI) scans of the brain
4. Safety and tolerability: Incidence of adverse events

Timepoint(s) of evaluation of this end point: 1. Up to 11 years
2. From baseline to Week 120
3. From baseline to Week 180
4. Up to 11 years

Secondary ID(s)

WA25046

2010-020338-25-LT

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 26/05/2011
Contact:

Results

• Results available: Yes
• Date Posted: 08/07/2016
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-020338-25/results