A Study to Evaluate Effectiveness and Safety of Ocrelizumab Treatment in Patients with Progressive Multiple Sclerosis

• Register: EUCTR
• Last refreshed on: 23 October 2023
• Main ID: EUCTR2017-001313-93-DK
• Date of registration: 23/02/2018
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A Study to Evaluate Effectiveness and Safety of Ocrelizumab Treatment in Patients with Progressive Multiple Sclerosis
• Scientific title: AN OPEN-LABEL, SINGLE-ARM 4-YEAR STUDY TO EVALUATE EFFECTIVENESS AND SAFETY OF OCRELIZUMAB TREATMENT IN PATIENTS WITH PROGRESSIVE MULTIPLE SCLEROSIS
• Date of first enrolment: 04/04/2018
• Target sample size: 900
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001313-93
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Algeria, Bosnia and Herzegovina, Brazil, Canada, Colombia, Costa Rica, Czech Republic, Czechia, Denmark, Egypt, France, Germany, Guatemala, Hungary, Ireland, Italy, Lebanon, Mexico, Morocco, Netherlands, Panama, Poland, Russian Federation, Spain, United Arab Emirates

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:
- Age 18-65 years
- Have a definite diagnosis of PMS (as per the revised McDonald 2010 criteria for PPMS or Lublin et al. 2014 criteria for PMS)
- Expanded Disability Status Scale (EDSS) <=6.5 at screening
- Able to comply with the study protocol, in the Investigator’s judgment
- Have documented evidence of disability progression independent of relapse activity at any point over the 2 years prior to the screening visit. In case relapse(s) have occurred in the last 2 years, disability progression will have to be considered as independent of relapse activity as per treating physician’s judgment
- Fulfill at least one of the 21 criteria assessing the evidence of disability progression independent of relapse activity in the last 2 years using the pre-baseline disability progression rating system checklist
- Have experience of having used a smartphone and connecting a smartphone to Wi-Fi network providers
- For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods during the treatment period and for at least 6 months, or longer if the local label is more stringent after the last dose of study drug (note: stricter contraception requirements should be followed in countries where mandated)
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 900
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Relapsing-remitting multiple sclerosis (RRMS) at screening.
- Inability to complete an MRI
- Gadolinium (Gd) intolerance
- Known presence of other neurological disorders, including but not limited to, the following:
o History of ischemic or haemorrhagic disorders of the brain or the spinal cord
o History or known presence of Central nervous system (CNS) or spinal cord tumour, or potential metabolic causes of myelopathy or infectious causes of myelopathy or systemic autoimmune disorders potentially causing progressive neurologic disease
o History of genetically inherited progressive CNS degenerative disorder
o Neuromyelitis optica.
o History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease
o History of severe, clinically significant brain or spinal cord trauma
Exclusions Related to General Health:
- Pregnancy or Lactation
- Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressant’s during the course of the study
- History of or currently active primary or secondary immunodeficiency
- Lack of peripheral venous access
- Significant or uncontrolled somatic disease or any other significant disease that may preclude the patient from participating in the study
- Active infections must be treated and resolved prior to the first infusion of ocrelizumab
- Patients in a severely immunocompromised state (until the condition resolves)
- Patients with known active malignancies or being actively monitored for recurrence of malignancy
- Patients who have or have had confirmed progressive multifocal leukoencephalopathy (PML)
Exclusions Related to Medications
Absolute exclusions:
- Previous treatment with ocrelizumab
- Hypersensitivity to ocrelizumab or to any of its excipients
- Previous treatment with B-cell targeted therapies Note: previous treatment with rituximab is allowed as long as the last dose was administered more than 6 months before the ocrelizumab infusion AND if discontinuation was due to adverse events or immunogenicity AND if B-cell levels are above the lower limit of normal (LLN) prior to screening
- Any previous treatment with alemtuzumab, total body irradiation, or bone marrow transplantation.
- Previous treatment with natalizumab where PML has not been excluded according to a specific algorithm
- Contraindications to or intolerance of oral or intravenous (IV) corticosteroids
Relative exclusions:
4 to 8 weeks prior to screening
- Systemic corticosteroid therapy within 4 weeks prior to screening
- All vaccines should be given at least 6 weeks before the first infusion of ocrelizumab , unless the local regulations allow for a shorter interval. Live/live attenuated vaccines should be avoided during treatment and safety follow-up period until B cells are peripherally repleted
- Previous treatment with, daclizumab or fingolimod in the last 8 weeks
- Treatment with fampridine/dalfampridine or other symptomatic MS treatment unless on stable dose for >=30 days prior to screening. Wherever possible, patients should remain on stable doses throughout the treatment period
12 weeks prior to screening
- Previous treatment with natalizumab, azathioprine, cyclophosphamide, mycophenolate mofetil or methotrexate in the last 12 weeks
24 weeks prior to screening
- Treatment with any investigational agent within 24 weeks of screening or five half-lives of the investigational drug or treatment (whichever is longer) with any experimental proced

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

Health Condition(s) or Problem(s) studied

Progressive multiple sclerosis (PMS)
MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 21.1 Level: PT Classification code 10053395 Term: Progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

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

Intervention(s)

Product Name: Ocrelizumab
Product Code: RO4964913
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Ocrelizumab
CAS Number: 637334-45-3
Current Sponsor code: RO4964913
Other descriptive name: OCRELIZUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-

Trade Name: Ocrevus
Product Name: Ocrelizumab
Product Code: RO4964913
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Ocrelizumab
CAS Number: 637334-45-3
Current Sponsor code: RO4964913
Other descriptive name: OCRELIZUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-

Primary Outcome(s)

Main Objective: •To evaluate the effectiveness of ocrelizumab treatment in patients with PMS disease course

Primary end point(s): 1. Proportion of patients with no evidence of progression (NEP) sustained for at least 24 weeks
2. Proportion of patients with NEP and no active disease (NEPAD) sustained for at least 24 weeks

Secondary Objective: •To evaluate the effectiveness of ocrelizumab treatment in PMS patients using a range of patient-relevant measures and imaging outcomes
•To evaluate the safety and tolerability of ocrelizumab in PMS patients

Timepoint(s) of evaluation of this end point: 1-2. From baseline to Week 96, Week 96 to Week 192 and baseline to Week 192

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1-3. From baseline to Weeks 48, 96, 144, 192
4-6. From baseline to Week 192
7-8. From Week 24 to Week 96, Week 24 to Week 192 and Week 48 to Week 192
9. From baseline to Week 96, Week 96 to Week 192 and baseline to Week 192
10-11. From baseline to Weeks 48, 96, 144, 192
12-15. From baseline to Week 192

Secondary end point(s): 1. Change from baseline in cognitive function as measured by the Symbol Digit Modalities Test (SDMT) and the Brief Visuospatial Memory Test – Revised (BVMT-R)
2. Change from baseline in the patient-reported outcomes including Multiple Sclerosis Impact Scale -29, Multiple Sclerosis Walking scale -12 items, ABILHAND-56 Questionnaire, Fatigue Scale for Motor and Cognitive (FSMC) function, SymptoMScreen, 88-item Multiple Sclerosis Spasticity Scale, Numerical Pain Rating Scale, Patient Global Impression of Severity (PGIS) for upper limb, lower limb and cognitive functions
3. Mean change from baseline in the EDSS score over the course of the study
4. Time to onset of first confirmed disability progression (as measured by EDSS) sustained for at least 24 and 48 weeks
5. Time to onset of first >=20% increase in timed 25-foot walk test sustained for at least 24 weeks
6. Time to onset of first >=20% increase in 9-hole peg test sustained for at least 24 weeks
7. Proportion of patients with NEP
8. Proportion of patients with NEPAD
9. Proportion of patients with confirmed disability improvement sustained for at least 24 weeks
10. Change in the following MRI volumetric measures: whole brain volume, cerebral white matter volume change, cortical gray matter volume, deep grey matter volume, thalamic volumes, whole and regional cerebellar volume
11. Change in the following lesion and tissue integrity parameters:
• Number of new/enlarging T2 lesions and Total T2 lesion volume
• Number of T1 Gd+ lesions and total volume
• Number of T1 lesions and total volume
• Gd-enhancing fluid-attenuated inversion-recovery (FLAIR) meningeal lesions
12. Rate and nature of adverse events
13. Changes in clinical laboratory results
14. Rates of study treatment discontinuation due to adverse events
15. Change in the number of falls and near-falls

Secondary ID(s)

2017-001313-93-IE

MN39159

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 04/04/2018
Contact: