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

An Open-Label, Single-Arm Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Patients With Early Stage Relapsing Remitting Multiple Sclerosis
Stopped earlyPhase 3Relapsing MSNCT030858102016-002937-31

What it found

Stopped: not working

The trial was stopped early because the treatment was not working.

Reason given: The study was terminated earlier as the study sponsor collected sufficient data to perform all analyses as per pre-specified endpoints in the study protocol.

What was tested

Treatment tested

Results by group

Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks and 48 Weeks as Measured Using Expanded Disability Status Scale (EDSS)

Baseline up to 4 years

GroupValueIntervalNumber analysed
OcrelizumabNot reached678
OcrelizumabNot reached678

Percentage of Participants With 24-Week and 48-Week Confirmed Disability Improvement (CDI) During the Year 1 Treatment Period, as Measured Using EDSS

At Weeks 24 and 48 during Year 1

GroupValueIntervalNumber analysed
Ocrelizumab95.11 Percentage of Participants92.03–97.03309
Ocrelizumab83.50 Percentage of Participants78.81–87.24309
Ocrelizumab87.54 Percentage of Participants83.28–90.77309

Ocrelizumab

95.11

Ocrelizumab

83.5

Ocrelizumab

87.54

Percentage of Participants Event-Free for CDP Sustained for at Least 24 and 48 Weeks at Year 1, as Measured Using EDSS

Year 1 (Weeks 24 and 48)

GroupValueIntervalNumber analysed
Ocrelizumab99.55 Percentage of Participants98.62–99.86678
Ocrelizumab97.30 Percentage of Participants95.75–98.29678
Ocrelizumab98.05 Percentage of Participants96.67–98.87678

Ocrelizumab

99.55

Ocrelizumab

97.3

Ocrelizumab

98.05

Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS

At Weeks 48, 72 and 96 during Year 2

GroupValueIntervalNumber analysed
Ocrelizumab100.0 Percentage of Participants100–100252
Ocrelizumab100.00 Percentage of Participants100–100252
Ocrelizumab97.20 Percentage of Participants94.22–98.66252
Ocrelizumab97.60 Percentage of Participants94.74–98.91252
Ocrelizumab90.29 Percentage of Participants85.71–93.46252
Ocrelizumab92.55 Percentage of Participants88.41–92.55252

Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 2, as Measured Using EDSS

Year 2 (Weeks 72 and 96)

GroupValueIntervalNumber analysed
Ocrelizumab93.97 Percentage of Particiopants91.87–95.54678
Ocrelizumab95.18 Percentage of Particiopants93.25–96.56678
Ocrelizumab91.65 Percentage of Particiopants89.26–93.52678
Ocrelizumab93.47 Percentage of Particiopants91.3–95.12678

Ocrelizumab

93.97

Ocrelizumab

95.18

Ocrelizumab

91.65

Ocrelizumab

93.47

Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS

At Weeks 144, 168 and 192 during Year 4

GroupValueIntervalNumber analysed
Ocrelizumab100.00 Percentage of Participants100–100678
Ocrelizumab100.00 Percentage of Participants100–100678
Ocrelizumab99.54 Percentage of Participants96.77–99.93678
Ocrelizumab100.00 Percentage of Participants100–100678
Ocrelizumab93.77 Percentage of Participants89.51–96.34678
Ocrelizumab98.01 Percentage of Participants94.77–99.25678

Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 4, as Measured Using EDSS

Year 4 (Weeks 168 and 192)

GroupValueIntervalNumber analysed
Ocrelizumab85.98 Percentage of Participants83.04–88.44678
Ocrelizumab87.98 Percentage of Participants85.2–90.27678
Ocrelizumab84.18 Percentage of Participants81.08–86.81678
Ocrelizumab86.48 Percentage of Participants83.54–88.93678

Ocrelizumab

85.98

Ocrelizumab

87.98

Ocrelizumab

84.18

Ocrelizumab

86.48

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

Year 1 (Week 48)

GroupValueIntervalNumber analysed
Ocrelizumab9.3 Percentage of Participants659
Ocrelizumab73.3 Percentage of Participants659
Ocrelizumab17.5 Percentage of Participants659

Ocrelizumab

9.3

Ocrelizumab

73.3

Ocrelizumab

17.5

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

Year 2 (Week 96)

GroupValueIntervalNumber analysed
Ocrelizumab11.9 Percentage of Participants632
Ocrelizumab76.6 Percentage of Participants632
Ocrelizumab11.6 Percentage of Participants632

Ocrelizumab

11.9

Ocrelizumab

76.6

Ocrelizumab

11.6

Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 3, As Measured Using EDSS

Year 3

GroupValueIntervalNumber analysed
Ocrelizumab9.3 Percentage of Participants557
Ocrelizumab81.5 Percentage of Participants557
Ocrelizumab9.2 Percentage of Participants557

Ocrelizumab

9.3

Ocrelizumab

81.5

Ocrelizumab

9.2

Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 4, As Measured Using EDSS

Year 4

GroupValueIntervalNumber analysed
Ocrelizumab18.0 Percentage of Participants562
Ocrelizumab59.3 Percentage of Participants562
Ocrelizumab22.8 Percentage of Participants562

Ocrelizumab

18

Ocrelizumab

59.3

Ocrelizumab

22.8

Mean Change From Baseline in EDSS Score at Week 24

From Baseline to Week 24

GroupValueIntervalNumber analysed
Ocrelizumab-0.14 Change in Total EDSS Score0.68 (Standard Deviation)671

Mean Change From Baseline in EDSS Score at Week 48

From Baseline to Week 48

GroupValueIntervalNumber analysed
Ocrelizumab-0.14 Change in Total EDSS Score0.77 (Standard Deviation)659

Mean Change From Baseline in EDSS Score at Week 72

From Baseline to Week 72

GroupValueIntervalNumber analysed
Ocrelizumab-0.09 Change in Total EDSS Score0.89 (Standard Deviation)651

Mean Change From Baseline in EDSS Score at Week 96

Baseline, Week 96

GroupValueIntervalNumber analysed
Ocrelizumab-0.12 Change in Total EDSS Score0.95 (Standard Error)637

Mean Change From Baseline in EDSS Score at Week 120

Baseline, Week 120

GroupValueIntervalNumber analysed
Ocrelizumab-0.10 Change in Total EDSS Score0.94 (Standard Deviation)579

Mean Change From Baseline in EDSS Score at Week 144

Baseline, Week 144

GroupValueIntervalNumber analysed
Ocrelizumab-0.10 Change in Total EDSS Score1 (Standard Error)561

Mean Change From Baseline in EDSS Score at Week 168

Baseline, Week 168

GroupValueIntervalNumber analysed
Ocrelizumab-0.05 Change in Total EDSS Score1.05 (Standard Error)560

Mean Change From Baseline in EDSS Score at Week 192

Baseline, Week 192

GroupValueIntervalNumber analysed
Ocrelizumab-0.06 Change in Total EDSS Score1.06 (Standard Deviation)562

Percentage of Participants Without Protocol-Defined Event of Disease Activity

Baseline up to 4 years

GroupValueIntervalNumber analysed
Ocrelizumab95.98 Percentage of participants94.2–97.23678
Ocrelizumab88.94 Percentage of participants86.3–91.09678
Ocrelizumab83.94 Percentage of participants80.92–86.52678
Ocrelizumab80.38 Percentage of participants77.14–83.21678
Ocrelizumab77.38 Percentage of participants73.99–80.39678
Ocrelizumab75.76 Percentage of participants72.28–78.86678
Ocrelizumab72.79 Percentage of participants69.18–76.05678
Ocrelizumab70.67 Percentage of participants66.97–74.04678

Percentage of Participants Without Relapse

Baseline up to 4 years

GroupValueIntervalNumber analysed
Ocrelizumab98.52 Percentage of Participants97.26–99.2678
Ocrelizumab97.91 Percentage of Participants96.5–98.76678
Ocrelizumab96.25 Percentage of Participants94.49–97.45678
Ocrelizumab95.32 Percentage of Participants93.41–96.69678
Ocrelizumab93.90 Percentage of Participants91.78–95.49678
Ocrelizumab93.09 Percentage of Participants90.85–94.79678
Ocrelizumab92.43 Percentage of Participants90.1–94.23678
Ocrelizumab91.56 Percentage of Participants89.12–93.48678

Annualized Relapse Rate

Baseline up to 4 years

GroupValueIntervalNumber analysed
Ocrelizumab0.02 events per participant per year0.015–0.027678

Sub Study: Number of Participants With IRRs Occurring During or Within 24 Hours Following the First Infusion After Randomization to the Shorter Infusion Substudy

Week 24 through Week 144

GroupValueIntervalNumber analysed
Substudy - Conventional Infusion101 Participants373
Substudy - Shorter Infusion107 Participants372

Substudy - Conventional Infusion

101

Substudy - Shorter Infusion

107

Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.

Safety

GroupParticipants at riskSerious adverse eventsDeaths
Ocrelizumab1225184 (15.0%)13
Substudy - Conventional Infusion37021 (5.7%)2
Substudy - Shorter Infusion37519 (5.1%)1

As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.

What it measured

Main measures

  • Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks and 48 Weeks as Measured Using Expanded Disability Status Scale (EDSS)

    Baseline up to 4 years

    Disability progression

  • Percentage of Participants With 24-Week and 48-Week Confirmed Disability Improvement (CDI) During the Year 1 Treatment Period, as Measured Using EDSS

    At Weeks 24 and 48 during Year 1

    Disability progression

  • Percentage of Participants Event-Free for CDP Sustained for at Least 24 and 48 Weeks at Year 1, as Measured Using EDSS

    Year 1 (Weeks 24 and 48)

    Disability progression

  • Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS

    At Weeks 48, 72 and 96 during Year 2

    Disability progression

  • Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 2, as Measured Using EDSS

    Year 2 (Weeks 72 and 96)

    Disability progression

  • Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS

    At Weeks 144, 168 and 192 during Year 4

    Disability progression

  • Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 4, as Measured Using EDSS

    Year 4 (Weeks 168 and 192)

    Disability progression

  • Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 1, As Measured Using EDSS

    Year 1 (Week 48)

    Disability progression

  • Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 2, As Measured Using EDSS

    Year 2 (Week 96)

    Disability progression

  • Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 3, As Measured Using EDSS

    Year 3

    Disability progression

  • Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 4, As Measured Using EDSS

    Year 4

    Disability progression

  • Mean Change From Baseline in EDSS Score at Week 24

    From Baseline to Week 24

    Disability progression

  • Mean Change From Baseline in EDSS Score at Week 48

    From Baseline to Week 48

    Disability progression

  • Mean Change From Baseline in EDSS Score at Week 72

    From Baseline to Week 72

    Disability progression

  • Mean Change From Baseline in EDSS Score at Week 96

    Baseline, Week 96

    Disability progression

  • Mean Change From Baseline in EDSS Score at Week 120

    Baseline, Week 120

    Disability progression

  • Mean Change From Baseline in EDSS Score at Week 144

    Baseline, Week 144

    Disability progression

  • Mean Change From Baseline in EDSS Score at Week 168

    Baseline, Week 168

    Disability progression

  • Mean Change From Baseline in EDSS Score at Week 192

    Baseline, Week 192

    Disability progression

  • Percentage of Participants Without Protocol-Defined Event of Disease Activity

    Baseline up to 4 years

    Disability progressionRelapsesMRI lesionsFatigue

  • Percentage of Participants Without Relapse

    Baseline up to 4 years

    Disability progressionRelapsesFatigue

  • Annualized Relapse Rate

    Baseline up to 4 years

    Disability progressionRelapsesMRI lesionsFatigue

  • Sub Study: Number of Participants With IRRs Occurring During or Within 24 Hours Following the First Infusion After Randomization to the Shorter Infusion Substudy

    Week 24 through Week 144

  • Disease progression

Other measures (26)

  • Percentage of Participants Who Are Relapse Free

    Week 192

    Disability progressionRelapsesFatigue

  • Percentage of Participants With No Evidence of Protocol Defined Disease Activity

    Weeks 96, 144, 192

    Disability progressionRelapsesMRI lesionsFatigue

  • Percentage of Participants Without Protocol-defined Event of Evidence of Progression (NEP)

    Weeks 96, 192

    Disability progressionWalking and mobility

  • Percentage of Participants With no Evidence of Progression Sustained for At Least 24 Weeks and no Active Disease (NEPAD)

    Weeks 96, 192

    Disability progressionRelapsesMRI lesionsFatigue

  • Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total

    Weeks 24, 48, 72, 96, 120, 144, 168, 192

    Disability progressionThinking and memoryWalking and mobility

  • Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score.

    Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192

    Disability progressionWalking and mobility

  • Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score

    Weeks 24, 48, 72, 96, 120, 144, 168, 192

    Disability progression

  • Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score

    Weeks 24, 48, 72, 96, 120, 144, 168, 192

    Disability progressionThinking and memory

  • Change From Baseline in Cognitive Performance as Measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) - Symbol Digits Modalities Test (SDMT)

    Baseline, Weeks 48, 96, 144, 192

    Thinking and memory

  • Change From Baseline in Cognitive Performance as Measured by BICAMS -California Verbal Learning Test-II (CVLT-II)

    Baseline, Weeks 48, 96, 144, 192

    Thinking and memory

Who could take part

Relapsing MS · 18 to 55

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 (\</=) 3 years * 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

As registered. Criteria can change, so ask the trial team or your neurologist.

About this trial

In the sponsor's words

This is a prospective, multicenter, open-label, single-arm, phase 3b study which evaluates effectiveness and safety of ocrelizumab in participants with early stage RRMS. The study will consist of an open-label treatment period of 192 weeks and follow-up period of at least 48 weeks. The optional shorter infusion substudy will evaluate the safety of a shorter infusion of ocrelizumab in a subgroup of participants with early stage RRMS enrolled in the main MA30143 study. Approximately 700 patients will be enrolled in the substudy, and will receive additional 600 mg ocrelizumab administered in a shorter time frame.

Papers

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Related trials

History

    1. Started

      Mar 2017

    2. Main results due

      Apr 2023

    3. Finished

      Apr 2023

    4. Results posted

      Jan 2025

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