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Active, Not Recruiting

NCT Number: NCT04544436

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

This is a randomized, double-blind, controlled, parallel group, multicenter study to evaluate efficacy, safety and PK of a higher dose of ocrelizumab per intravenous (IV) infusion every 24 weeks (Q24W) in participants with RMS, in comparison to the approved 600 milligrams (mg) dose of ocrelizumab.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Immune System Diseases Multiple Sclerosis, Relapsing-Remitting Nervous System Diseases

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

CEMIC, Buenos Aires, Argentina

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About this study

Participants will be treated for a minimum of 120 weeks in the double-blind treatment (DBT) phase. Upon positive primary results after the DBT phase, an optional higher dose extension treatment, open-label extension (OLE) phase is planned for eligible participants. The OLE will be carried out for approximately 96 weeks. Participants will be followed for safety for 48 weeks thereafter. Participants whose B-cell levels still did not replete to their baseline level or the low level of normal (LLN), whichever is lower, will move into the B-cell monitoring (BCM) phase following the safety follow-up phase. The study will end when all participants who were not treated with an alternative B-cell depleting therapy have repleted their B-cells to the baseline value or the LLN.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ocrelizumab

Drug

The actual higher dose of ocrelizumab will be assigned to participants based on their body weight at baseline: 1200 mg (body weight <75 kg) or 1800 mg (body weight ≥ 75 kg). The first dose of ocrelizumab will be administered as two 600 mg or 900 mg IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 1200 mg or 1800 mg IV infusion Q24W. During the optional OLE phase, participants will continue with their assigned dose of ocrelizumab (either 1200 or 1800 mg) for approximately 96 weeks (4 doses in total).

Other names: Ocrevus

Antihistamine

Drug

Premedication with oral or IV antihistaminic drug (i.e., diphenhydramine 50 mg or an equivalent dose of an alternative) will be administered prior to each ocrelizumab infusion.

Other names: Non-Investigational Medicinal Product

methylprednisolone

Drug

Premedication with 100 mg of methylprednisolone (or equivalent) will be administered by IV infusion prior to each ocrelizumab infusion.

Other names: Non-Investigation Medicinal Product

Primary outcomes

  1. Time to Onset of 12-week Composite Confirmed Disability Progression (cCDP12)

    Time frame: Up to approximately 4 years

    Time to onset of 12-week cCDP=first occurrence of a 12-week cCDP according to at least 1 of the 3 criteria: 1) CDP=12-week confirmed increase (CI) from baseline (FB) in expanded disability status scale (EDSS) score of ≥1.0 point in participants with baseline EDSS score of ≤5.5 or 12-week CI≥0.5 point in participants with baseline EDSS score of >5.5 OR 2) 12-week CI of ≥20% FB in Timed 25-foot Walk Test (T25FWT) score OR 3)12-week CI of ≥ 20% FB in 9-hole Peg Test (9-HPT) score. EDSS = disability scale that ranges in 0.5-point steps from 0 [normal]-10.0 [death]. In T25FWT test participants walked to a 25 foot course as quickly & safely as possible. Score = average of 2 completed trials (in seconds). In 9-HPT, participants had to place & remove pegs 1 by 1 into 9 holes arranged in a board & complete 2 successful trials for each hand & the amount of time (in seconds) required was recorded. In T25FWT & 9-HPT the longer it took complete test= higher scores, indicating deterioration.

Secondary outcomes

  1. Time to Onset of 24-week cCDP (cCDP24)

    Time frame: Up to approximately 4 years

    Time to onset of a 24 week cCDP=first occurrence of a 24-week cCDP according to at least 1 of 3 criteria: 1) CDP=24-week CI from baseline in EDSS score of ≥1.0 point in participants with baseline EDSS score of ≤5.5 or 24-week CI≥0.5 point in participants with baseline EDSS score of >5.5 OR 2) 24-week CI of ≥20% FB in T25FWT score OR 3) 24-week CI of ≥ 20% FB in 9-HPT score. EDSS = disability scale that ranges in 0.5-point steps from 0 [normal]-10.0 [death]. In T25FWT test participants walked to a 25 foot course as quickly & safely as possible. Score = average of 2 completed trials (in seconds). In 9-HPT, participants had to place & remove pegs 1 by 1 into 9 holes arranged in a board & complete 2 successful trials for each hand & the amount of time (in seconds) required was recorded. In T25FWT & 9-HPT the longer it took complete test= higher scores, indicating deterioration.

  2. Time to Onset of 48-week cCDP (cCDP48)

    Time frame: Up to approximately 4 years

    Time to onset of a 48-week cCDP=first occurrence of a 48-week cCDP according to at least 1 of 3 criteria: 1) CDP=48-week CI from baseline in EDSS score of ≥1.0 point in participants with baseline EDSS score of ≤5.5 or 48-week CI≥0.5 point in participants with baseline EDSS score of >5.5 OR 2) 48-week CI of ≥20% FB in T25FWT score OR 3) 48-week CI of ≥ 20% FB in 9-HPT score. EDSS = disability scale that ranges in 0.5-point steps from 0 [normal]-10.0 [death]. In T25FWT test participants walked to a 25 foot course as quickly & safely as possible. Score = average of 2 completed trials (in seconds). In 9-HPT, participants had to place & remove pegs 1 by 1 into 9 holes arranged in a board & complete 2 successful trials for each hand & the amount of time (in seconds) required was recorded. In T25FWT & 9-HPT the longer it took complete test= higher scores, indicating deterioration.

  3. Time to Onset of cCDP12 Independent of Protocol-defined Relapses (PDR) or Progression Independent of Relapse Activity (PIRA)

    Time frame: Up to approximately 4 years

    Time to onset of 12-week cCDP=first occurrence of a 12-week cCDP according to at least 1 of 3 criteria: 1) CDP=12-week CI from baseline in EDSS score of ≥1.0 point in participants with baseline EDSS score of ≤5.5 or 12-week CI≥0.5 point in participants with baseline EDSS score of >5.5 OR 2) 12-week CI of ≥20% FB in T25FWT score OR 3) 12-week CI of ≥ 20% FB in 9-HPT score. EDSS score, T25FWT & 9-HPT are the same as defined in primary outcome measure. Protocol-defined relapse=occurrence of new or worsening neurological symptoms attributable to MS and immediately preceded by a relatively stable or improving neurological state of at least 30 days. Symptoms persist for at least 24 hours & accompanied by objective neurological worsening consistent with an increase of one of the following: Half a step (0.5 point) on the EDSS; Two points on one of the functional system scores (FSS) (pyramidal, ambulation, cerebellar, brainstem, sensory, or visual); One point on ≥2 more of the FSS.

  4. Time to Onset of 12-week Confirmed Disability Progression (CDP12)

    Time frame: Up to approximately 4 years

    CDP was defined as a 12-week confirmed increase from baseline in EDSS score of ≥1.0 point in participants with a baseline EDSS score of ≤5.5 or a 12-week CI ≥0.5 points in participants with a baseline EDSS score of >5.5. The EDSS was used to measure changes in the disability level of participants with MS over time. EDSS is based on a standard neurological examination, incorporating functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral [or mental]) that are rated and then scored as a FSS, and ambulation, which is scored as ambulation score. Each FSS is an ordinal clinical rating scale where score range from 0 to 5 or 6, and ambulation score that is rated from 0 to 16. These ratings along with observations and assistive devices were then used to determine the total EDSS score. The total EDSS score ranges from 0 (normal) to 10.0 (death) in 0.5-point steps.

  5. Time to ≥ 20% Increase in 12-week Confirmed T25FWT

    Time frame: Up to approximately 4 years

    T25FWT test is a performance measure used to assess walking speed based on a timed 25-foot walk. The participant was directed to start at one end of a clearly marked 25-foot course and was instructed to walk 25 feet as quickly and safely as possible. The Examining Investigator timed the participants from the start of the walk to the end of the 25 feet. The task was immediately administered again by having the participant walk back the same distance. Participants could use assistive devices (e.g., cane, crutch, or rollator) when performing the task. Score was the average of the two completed trials, measured in seconds. The longer it takes to walk, higher the score, indicating deterioration. A 20% change from baseline of the averaged T25FWT was considered clinically meaningful.

  6. Annual Rate of Percent Change From Baseline in Total Brain Volume

    Time frame: Up to approximately 4 years

    Brain volume was measured using magnetic resonance imaging (MRI) scans. Mean difference in annual rate of percent change from baseline in total brain volume between the higher and approved dose of ocrelizumab arms in participants with RMS where no treatment discontinuation nor initiation of alternative MS treatment occurred, are reported.

  7. Time to Onset of 12-week Confirmed 4-point Worsening in Symbol Digit Modality Test (SDMT)

    Time frame: Up to approximately 4 years

    The SDMT is a performance measure that demonstrated sensitivity in detecting the presence of cognitive impairment and changes in cognitive functioning over time & in response to treatment. The SDMT presents a series of nine symbols, each paired with a single digit in a key at the top of a standard sheet of paper. Participants were asked to pair specific numbers with given geometric figures within 90 seconds. Responses were collected orally. The score is the number of correctly paired items in 90 seconds with a maximum score of 110 and minimum of 0. Higher scores indicate improvement. A four-point change from baseline was considered clinically meaningful.

  8. Time to Onset of 24-week Confirmed 8-point Increase in 12-item Multiple Sclerosis Walking Scale (MSWS-12)

    Time frame: Up to approximately 4 years

    The MSWS-12 was a 12-item self-report measure of the impact of MS on the participant's ability to walk during the past 2 weeks. Each item was scored on a 5-point Likert scale ranging from 1 (not at all) to 5 (extremely likely). Scores were summed and linearly converted to a 0-100 scale with higher scores indicating greater impact of MS on walking ability. An 8-point change was considered clinically meaningful.

  9. Fold Change From Baseline in Neurofilament Light (NfL) Chain at Week 48 for Participants Assigned to the Higher Dose Ocrelizumab Group

    Time frame: Week 48

    NfL is a biomarker of neuroinflammation in CSF. Ratio of change from baseline in NfL at Week 48 for RMS participants where no treatment discontinuation nor initiation of alternative MS treatment occurred within the ocrelizumab higher dose arm has been reported. The results correspond to fold change from baseline (ie ratio of adjusted geometric means at week 48 vs baseline).

  10. Fold Change From Baseline in NfL Chain at Week 48 for Participants Assigned to the Approved Dose Ocrelizumab Group

    Time frame: Week 48

    NfL is a biomarker of neuroinflammation in CSF. Ratio of change from baseline in NfL at Week 48 for RMS participants where no treatment discontinuation nor initiation of alternative MS treatment occurred within the ocrelizumab approved dose arm has been reported. The results correspond to fold change from baseline (ie ratio of adjusted geometric means at week 48 vs baseline).

  11. Number of Participants With Adverse Events (AEs)

    Time frame: From initiation of study drug up to approximately 4 years

    AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

  12. Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab Over the First Dosing Interval

    Time frame: Day 1 to Week 24

  13. B-cell Levels in Blood

    Time frame: Baseline, Weeks 2, 24, 48, 72, 96, 120, 144, 168, and 192

  14. Percent Change From Baseline in B-cell Levels

    Time frame: Weeks 2, 24, 48, 72, 96, 120, 144, 168, and 192

  15. Percentage of Participants Who Achieved ≤ 5 B-cells/μL of Blood

    Time frame: Baseline, Weeks 2, 24, 48, 72, 96, 120, 144, 168, and 192

  16. Percentage of Participants With Anti-drug Antibodies (ADAs) to Ocrelizumab

    Time frame: Baseline up to approximately 4 years

    Prevalence of ADAs at baseline was defined as the percentage of participants that is ADA positive at baseline. For determining post-baseline incidence, participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 titer unit (t.u.) greater than the baseline titer result. Percentages have been rounded off.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Acronym: MUSETTE

Important dates

Study start
2020
Primary completion
2024
Study completion
2028
First posted
Sep 10, 2020
Registry last updated
Jul 30, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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