A Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Patients with Early Stage Relapsing Remitting Multiple Sclerosis

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2016-002937-31-BE
• Date of registration: 05/05/2017
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Patients with Early Stage Relapsing Remitting Multiple Sclerosis
• Scientific title: An Open-Label, single-arm study to evaluate the effectiveness and safety of Ocrelizumab in patients with early stage relapsing remitting multiple sclerosis
• Date of first enrolment: 10/07/2017
• Target sample size: 1225
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002937-31
• 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

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Croatia, Denmark, France, Germany, Hungary, Italy, Kuwait, Lebanon, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, 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:
- Able to comply with the study protocol, in the investigator’s judgment
- Age 18 - 55 years, inclusive
- Have a definite diagnosis of RRMS, as per the revised McDonald 2010 criteria
- Have a length of disease duration, from first documented clinical attack consistent with multiple sclerosis (MS) disease of <= 3 years
- Within the last 12 months: one or more clinically reported relapse(s) or one or more signs of MRI activity
- Expanded Disability Status Scale (EDSS) of 0.0 to 3.5 inclusive, at screening
- For women of childbearing potential: agreement to use an acceptable birth control method during the treatment period and for at least 6 months or longer after the last dose of ocrelizumab, as applicable in the ocrelizumab package leaflet

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 1225
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Secondary progressive multiple sclerosis or history of primary progressive or progressive relapsing MS
- Inability to complete a Magnetic resonance imaging (MRI)
- Known presence of other neurological disorders, including but not limited to, the following:
• History of ischemic cerebrovascular disorders or ischemia of the spinal cord
• History or known presence of central nervous system (CNS) or spinal cord tumor
• History or known presence of potential metabolic causes of myelopathy
• History or known presence of infectious causes of myelopathy
• History of genetically inherited progressive CNS degenerative disorder
• Neuromyelitis optica
• History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease
• History of severe, clinically significant brain or spinal cord trauma
Exclusions Related to General Health
- Pregnancy or lactation
- Patients intending to become pregnant during the study or within 6 months after the last dose of the study drug
- Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
- History or currently active primary or secondary immunodeficiency
- Lack of peripheral venous access
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- Significant or uncontrolled somatic disease or any other significant disease that may preclude patient from participating in the study
- Congestive heart failure [NYHA] III or IV functional severity).
- Known active bacterial, viral, fungal, mycobacterial infection or other infection, or any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks prior to screening or oral antibiotics 2 weeks prior to screening
- History of major opportunistic infections
- History or known presence of recurrent or chronic infection
- History of malignancy, including solid tumors and hematological malignancies
- History of alcohol or drug abuse within 24 weeks prior to baseline
- History or laboratory evidence of coagulation disorders
Exclusions Related to Medications
- Received any prior approved Disease modifying treatment (DMT) with a label for MS, for example, interferons, glatiramer acetate, natalizumab, alemtuzumab, daclizumab, fingolimod, teiflunomide and dimethylfumarate
- Received a live vaccine or attenuated live vaccine within 6 weeks prior to the baseline visit
- Treatment with any investigational agent within 24 weeks of screening or five half-lives of the investigational drug or treatment with any experimental procedures for MS
- Contraindications to or intolerance of oral or intravenous (IV) corticosteroids, including methylprednisolone administered IV, according to the country label
- Previous treatment with B-cell targeted therapies
- Systemic corticosteroid therapy within 4 weeks prior to screening.
- Any previous treatment with immunosuppressants/ immunomodulators/ antineoplastic therapies
- Treatment with IV Immunoglobulin within 12 weeks prior to baseline
- Treatment with investigational DMT
- History of recurrent aspiration pneumonia requiring antibiotic therapy
- Treatment with fampridine/dalfamipridine unless on stable dose for = 30 days prior to screening. Wherever possible, patients should remain on stable doses throughout the 96-week treatment period
Exclusion

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

Health Condition(s) or Problem(s) studied

Relapsing remitting multiple sclerosis (RRMS)
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 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: PT Classification code 10048393 Term: Multiple sclerosis relapse System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.1 Level: LLT Classification code 10039720 Term: Sclerosis multiple System Organ Class: 10029205 - Nervous system disorders

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

Intervention(s)

Product Name: Ocrelizumab
Product Code: RO4964913/F07-01
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/F07-01
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)

Primary end point(s): Disease progression

Timepoint(s) of evaluation of this end point: Up to 4 years

Main Objective: To evaluate the effectiveness of ocrelizumab in early stage of RRMS

Secondary Objective: - To evaluate different clinical measures related to disease progression in early stage of RRMS disease
- To evaluate the safety and tolerability of ocrelizumab in early stage of RRMS

Exploratory objectives:
The following Covid-19 related exploratory objective has been added to the study protocol version 10.0
-To investigate the effect of ocrelizumab on antibody and T cell
responses in patients administered an approved severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) vaccine

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1-23. Up to 4 years / 192 wks of the study duration, with interim assessments at week 48, 96, and 144

Secondary end point(s): 1. Time to onset of confirmed disability progression (CDP) sustained for at least 24 weeks and 48 weeks
2. Proportion of patients who have confirmed disability improvement (CDI), CDP for at least 24 weeks and 48 weeks at Years 1, 2 and 4
3. Proportion of patients who have improved, stable or worsened disability compared with baseline measured by EDSS annually
4. Mean change from baseline in EDSS score over the course of the study
5. Time to first protocol-defined event of disease activity
6. Time to first relapse
7. Annualized relapse rate
8. Proportion of patient relapse free by Weeks 48, 96, 144 and 192
9. Proportion of patients with no evidence of protocol-defined disease activity (NEDA) over Week 96, Week 144 and Week 192
10. Proportion of patients with no evidence of progression sustained for at least 24 weeks on all the following three components (CDP; 20% increase in timed 25 Foot Walk Test [T25FWT]; 20% increase in timed 9 hole peg test [9HPT]) between baseline and Week 96/192
11. Proportion of patients with no active disease between Baseline and Week 96/192
12. Change from baseline of multiple sclerosis functional composite (MSFC) and its composites (T25FW, 9HP, and Paced Auditory Serial Addition Test [PASAT]) over time
13. Change from baseline in cognitive performance as measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) performed annually
14. Total number of T1 Gd-enhancing lesions; and new and/or enlarging T2 lesion as detected by brain MRI over time
15. Change in T1 volume over time
16. Total number of fluid-attenuated inversion-recovery (FLAIR) lesion counts as detected by brain MRI over time
17. Change in brain volume (including white and grey matter fractions) as detected by brain MRI over time
18. Time to treatment discontinuation/switch
19. Employment status score (Work Productivity and Activity Impairment Questionnaire [WPAI])
20. SymptoMScreen score
21. Quality of life score (Multiple Sclerosis Impact Scale [MSIS]-29)
22. Rate and nature of adverse events
23. Changes in vital signs, physical and neurological examinations, clinical laboratory results, locally reviewed MRI for safety and concomitant medications

Secondary ID(s)

2016-002937-31-NO

MA30143

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 10/07/2017
Contact: