A Study to Evaluate the Efficacy, Safety and Pharmacokinetics (PK) of a Higher Dose of Ocrelizumab in Adults With Relapsing Multiple Sclerosis (RMS)

• Register: ClinicalTrials.gov
• Last refreshed on: 3 February 2025
• Main ID: NCT04544436
• Date of registration: 04/09/2020
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: A Study to Evaluate the Efficacy, Safety and Pharmacokinetics (PK) of a Higher Dose of Ocrelizumab in Adults With Relapsing Multiple Sclerosis (RMS) MUSETTE
• Scientific title: A Phase IIIb Multicenter, Randomized, Double-blind, Controlled Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults With Relapsing Multiple Sclerosis
• Date of first enrolment: November 26, 2020
• Target sample size: 864
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT04544436
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Mexico, Netherlands, Peru, Poland, Portugal, Russian Federation, Spain, Switzerland, Turkey, Ukraine, United Kingdom, United States

Contacts

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

Key inclusion & exclusion criteria

Inclusion Criteria:

- Diagnosis of RMS

- At least two documented clinical relapses within the last 2 years prior to
screening, or one clinical relapse in the year prior to screening. No relapse 30
days prior to screening and at baseline

- Participants must be neurologically stable for at least 30 days prior to
randomization and baseline

- EDSS score, at screening and baseline, from 0 to 5.5 inclusive

- Average T25FWT score over two trials at screening and over two trials at baseline
respectively, up to 150 (inclusive) seconds

- Average 9HPT score over four trials at screening and over four trials at baseline
respectively, up to 250 (inclusive) seconds

- Documented magnetic resonance imaging (MRI) of brain with abnormalities consistent
with MS at screening

- Participants requiring symptomatic treatment for MS and/or physiotherapy must be
treated at a stable dose. No initiation of symptomatic treatment for MS or
physiotherapy within 4 weeks of randomization

- Females of childbearing potential, agreement to remain abstinent or use adequate
contraceptive methods

- Female participants without reproductive potential may be enrolled e.g. if
post-menopausal or if surgically sterile

Exclusion Criteria:

- History of primary progressive MS at screening

- Any known or suspected active infection at screening or baseline (except nailbed
infections), or any major episode of infection requiring hospitalization or
treatment with IV antimicrobials within 8 weeks or treatment with oral
antimicrobials within 2 weeks, prior to and during screening

- History of confirmed or suspected progressive multifocal leukoencephalopathy

- History of cancer, including hematologic malignancy and solid tumors, within 10
years of screening

- Immunocompromised state

- Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization

- Inability to complete an MRI or contraindication to gadolinium administration

- Contraindications to mandatory pre-medications for infusion-related reaction (IRRs)

- Known presence of other neurologic disorders that could interfere with the diagnosis
of MS or assessments of efficacy and/or safety during the study

- Any concomitant disease that may require chronic treatment with systemic
corticosteroids or immunosuppressants during the course of the study

- Significant, uncontrolled disease that may preclude participant from participating
in the study

- History of or currently active primary or secondary, non-drug-related,
immunodeficiency

- Pregnant or breastfeeding or intending to become pregnant

- Lack of peripheral venous access

- History of alcohol or other drug abuse within 12 months prior to screening

- Treatment with any investigational agent within 24 weeks prior to screening or
treatment with any experimental procedure for MS

- Previous use of anti- cluster of differentiation 20 (CD20s) (including ocrelizumab),
unless the last infusion was more than 2 years before screening, B-cell count is
normal, and the stop of the treatment was not motivated by safety reasons or lack of
efficacy

- Previous treatment with fingolimod, siponimod, or ozanimod within 6 weeks of
baseline

- Previous treatment with natalizumab within 4.5 months of baseline

- Previous treatment with interferons beta (1a or 1b), or glatiramer acetate within 2
weeks of baseline

- Any previous treatment with mitoxantrone, cladribine, atacicept, alemtuzumab, and
daclizumab - Previous treatment with any other immunomodulatory or immunosuppressive
medication not already listed above without appropriate washout as described in the
applicable local label. If the washout requirements are not described in the
applicable local label, then the wash out period must be five times the half-life of
the medication

- Any previous treatment with bone marrow transplantation and hematopoietic stem cell
transplantation

- Any previous history of transplantation or anti-rejection therapy

- Treatment with IV immunoglobulin (Ig) or plasmapheresis within 12 weeks prior to
randomization

- Systemic corticosteroid therapy within 4 weeks prior to screening

- Positive screening tests for active, latent, or inadequately treated hepatitis B

- Sensitivity or intolerance to any ingredient (including excipients) of ocrelizumab

- Any additional exclusionary criterion as per ocrelizumab local label, if more
stringent than the above


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

Health Condition(s) or Problem(s) studied

Multiple Sclerosis

Intervention(s)

Drug: Antihistamine

Drug: Methylprednisolone

Drug: Ocrelizumab

Primary Outcome(s)

Time to Onset of 12-week Composite Confirmed Disability Progression (cCDP12) [Time Frame: Baseline up to approximately 4.3 years]

Secondary Outcome(s)

Time to Onset of 24-week cCDP (cCDP24) [Time Frame: Baseline up to approximately 4.3 years]

Time to = 20% Increase in 12-week Confirmed by T25FWT [Time Frame: Baseline up to approximately 4.3 years]

Serum Concentration of Ocrelizumab at Specified Time Points [Time Frame: Week 0, 2, 12, 24, 36, 48, 60, 72, 84, 96, 120]

Time to 12-week Confirmed 4-point Worsening in Symbol Digit Modality Test (SDMT) [Time Frame: Baseline up to approximately 4.3 years]

Annual Rate of Percent Change From Baseline in Total Brain Volume [Time Frame: Baseline up to approximately 4.3 years]

Time to Onset of 48-week cCDP (cCDP48) [Time Frame: Baseline up to approximately 4.3 years]

Percentage of Participants Achieving 5 or Less B-cells per Microliter of Blood [Time Frame: Baseline up to approximately 4.3 years]

Percentage of Participants With Adverse Events (AEs) [Time Frame: Baseline up to approximately 7.5 years]

B-cell Levels in Blood [Time Frame: Baseline up to approximately 4.3 years]

Change From Baseline in the Anti-drug Antibody (ADA) Levels [Time Frame: Week 0, 24, 48, 72, 96, 120]

Change in Neurofilament Light (NfL) at Week 48 for Participants Assigned to the Higher Dose Ocrelizumab Group [Time Frame: Baseline (Week 0), Week 48]

Time to Onset of 12-week Confirmed Disability Progression (CDP12) [Time Frame: Baseline up to approximately 4.3 years]

Time to Onset of cCDP12 Independent of Protocol-defined Relapses (PDR) [Time Frame: Baseline up to approximately 4.3 years]

Change in NfL at Week 48 for Participants Assigned to the Approved Dose Ocrelizumab Group [Time Frame: Baseline (Week 0), Week 48]

Time to 12-week Confirmed 8-point Increase in 12-item Multiple Sclerosis Walking Scale (MSWS-12) [Time Frame: Baseline up to approximately 4.3 years]

Secondary ID(s)

2023-506467-34-00

2020-000893-69

BN42082

Source(s) of Monetary Support

Please refer to primary and secondary sponsors