Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Participants With Early Stage Relapsing Remitting Multiple Sclerosis (RRMS)

• Register: ClinicalTrials.gov
• Last refreshed on: 6 November 2023
• Main ID: NCT03085810
• Date of registration: 16/03/2017
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Participants With Early Stage Relapsing Remitting Multiple Sclerosis (RRMS)
• 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: March 24, 2017
• Target sample size: 1239
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03085810
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Croatia, Denmark, Finland, France, Germany, Hungary, Italy, Kuwait, Lebanon, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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 MS disease of less than or equal to (
- Within the last 12 months one or more clinically reported relapse(s) or one or more
signs of MRI activity

- EDSS of 0.0 to 3.5 inclusive, at screening

- An agreement to use an acceptable birth control method for women of childbearing
potential, during the treatment period and for at least 6 months or longer after the
last dose of study drug

Exclusion Criteria:

- Secondary progressive multiple sclerosis or history of primary progressive or
progressive relapsing MS

- Inability to complete an MRI

- Known presence of other neurological disorders

Exclusions Related to General Health:

- Pregnancy or lactation

- Participants 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 participant from participating in the study

- Congestive heart failure (New York Heart Association III or IV functional severity)

- Known active bacterial, viral, fungal, mycobacterial infection or other infection,
(excluding fungal infection of nail beds) or any major episode of infection requiring
hospitalization or treatment with IV antibiotics within 4 weeks prior to screening or
oral antibiotics 2 weeks prior to screening

- History of malignancy, major opportunistic infections, alcohol or drug abuse,
recurrent or chronic infection, and/or 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

- Receipt of a live vaccine or attenuated live vaccine within 6 weeks prior to the
baseline visit

- Previous treatment with B-cell targeted therapies (i.e., rituximab, ocrelizumab,
atacicept, belimumab, or ofatumumab)

- Any previous treatment with immunosuppressants/ immunomodulators/ antineoplastic
therapies (cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine,
methotrexate, cladribine, mitoxantrone, laquinimod, total body irradiation, or bone
marrow transplantation)

- Treatment with investigational DMT

- Treatment with fampridine/dalfamipridine unless on stable dose for >/=30 days prior to
screening

Exclusion related to Shorter Infusion Substudy:

- Any previous serious IRRs experienced with ocrelizumab treatment



Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Sclerosis, Relapsing-Remitting

Intervention(s)

Drug: Ocrelizumab

Primary Outcome(s)

Mean Change From Baseline in EDSS Score at Week 192 [Time Frame: Baseline, Week 192]

Mean Change From Baseline in EDSS Score at Week 48 [Time Frame: Baseline, Week 48]

Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 1, As Measured Using EDSS [Time Frame: Year 1]

Percentage of Participants With Confirmed Disability Improvement (CDI) at Year 1, As Measured Using EDSS [Time Frame: Year 1]

Mean Change From Baseline in EDSS Score at Week 72 [Time Frame: Baseline, Week 72]

Percentage of Participants With CDI at Year 2, As Measured Using EDSS [Time Frame: Year 2]

Mean Change From Baseline in EDSS Score at Week 96 [Time Frame: Baseline, Week 96]

Mean Change From Baseline in EDSS Score at Week 120 [Time Frame: Baseline, Week 120]

Mean Change From Baseline in EDSS Score at Week 168 [Time Frame: Baseline, Week 168]

Percentage of Participants With CDP Sustained for At Least 24 and 48 Weeks at Year 1, As Measured Using EDSS [Time Frame: Year 1]

Proportion of Participants with Infusion Related Reactions (IRRs) Occurring During or Within 24 Hours Following the First Infusion After Randomization to the Shorter Infusion Substudy [Time Frame: From Week 24 through Week 192]

Time to First Protocol-Defined Event of Disease Activity [Time Frame: Baseline up to 4 years]

Annualized Relapse Rate [Time Frame: Baseline up to 4 years]

Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 3, As Measured Using EDSS [Time Frame: Year 3]

Percentage of Participants With CDP Sustained for At Least 24 and 48 Weeks at Year 2, As Measured Using EDSS [Time Frame: Year 2]

Time to First Relapse [Time Frame: Baseline up to 4 years]

Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 and 48 Weeks, As Measured Using Expanded Disability Status Scale (EDSS) [Time Frame: Baseline up to 4 years]

Mean Change From Baseline in EDSS Score at Week 24 [Time Frame: Baseline, Week 24]

Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 2, As Measured Using EDSS [Time Frame: Year 2]

Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 4, As Measured Using EDSS [Time Frame: Year 4]

Percentage of Participants With CDI at Year 4, As Measured Using EDSS [Time Frame: Year 4]

Percentage of Participants With CDP Sustained for At Least 24 and 48 Weeks at Year 4, As Measured Using EDSS [Time Frame: Year 4]

Mean Change From Baseline in EDSS Score at Week 144 [Time Frame: Baseline, Week 144]

Secondary Outcome(s)

Change from Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score [Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192]

Change from baseline in total T1 hypointense lesion volume as Detected by Brain MRI [Time Frame: Baseline, Weeks 8, 24, 48, 96, 144, 192]

Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score [Time Frame: Baseline, Weeks 24, 48, 96, 120, 144, 192]

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: Baseline up to 4 years]

Percentage of Participants With no Evidence of Progression Sustained for At Least 24 Weeks and no Active Disease (NEPAD) [Time Frame: Weeks 96, 192]

Percentage of Participants With no Evidence of Progression (NEP) [Time Frame: Weeks 96, 192]

Change from Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score [Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192]

Proportion of Participants with IRR (overall) in the Shorter Infusion Substudy [Time Frame: From Week 24 through Week 192]

Proportion of Participants with IRR By Dose at Randomization in the Shorter Infusion Substudy [Time Frame: From Week 24 through Week 192]

Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI [Time Frame: Baseline, Weeks 8, 24, 48, 96, 144, 192]

Change from Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score [Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192]

Percentage of Participants With No Evidence of Protocol Defined Disease Activity [Time Frame: Weeks 96, 144, 192]

Proportion of Participants with IRRs Leading to Treatment Discontinuation in the Shorter Infusion Substudy [Time Frame: From Week 24 through Week 192]

Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score [Time Frame: Baseline, Weeks 24, 48, 96, 120, 144, 192]

Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI [Time Frame: Baseline, Weeks 8, 24, 48, 96, 144, 192]

Change from baseline in cognitive performance as measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) [Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192]

Change from Baseline in Multiple Sclerosis Functional Composite (MSFC) Total Score [Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192]

Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI [Time Frame: Baseline, Weeks 8, 24, 48, 96, 144, 192]

SymptoMScreen Composite Score [Time Frame: Baseline, Weeks 24, 48, 96, 120, 144, 192]

Change From Baseline in Brain Volume as Detected by Brain MRI [Time Frame: Baseline, Weeks 8, 24, 48, 96, 144, 192]

Percentage of Participants Who Are Relapse Free [Time Frame: Weeks 48, 96, 144, 192]

Time to Treatment Discontinuation [Time Frame: Baseline up to 4 years]

Secondary ID(s)

MA30143

2016-002937-31

Source(s) of Monetary Support

Please refer to primary and secondary sponsors