Multiple Sclerosis, Primary Progressive, Relapsing Multiple Sclerorsis
Conditions
Brief summary
This is an open-label, multicenter, biomarker study designed to be hypothesis-generating in order to better understand the mechanism of action of ocrelizumab and B-cell biology in RMS or PPMS. The study will be conducted in two cohorts i.e. RMS cohort (4 arm group) and PPMS cohort (one arm group). RMS cohort: Ocrelizumab will be administered as two intravenous (IV) infusions of 300 milligrams (mg) on Days 1 and 15. Subsequent doses will be given as single 600-mg infusions at Weeks 24 and 48. Participants will be randomized in 1:1:1 ratio to receive lumbar puncture (LP) post-treatment at Week 12, 24, or 52 following the first dose of ocrelizumab in three arm groups. A fourth RMS arm with delayed treatment start (Arm 4 \[control group\]) will not be a part of the randomization and will be recruited separately, wherein treatment with ocrelizumab will be delayed for 12 weeks from pre-treatment baseline. PPMS cohort: Ocrelizumab 600 mg will be administered as two 300-mg IV infusions separated by 14 days at a scheduled interval of every 24 weeks. Participants will receive a LP at the start of the study before dosing with ocrelizumab and second LP at Week 52 following the first dose of ocrelizumab. A long-term extension will be conducted for participants that complete the study and continue to receive ocrelizumab. Treatment with ocrelizumab in the entire study will continue for approximately 4.5 years after the first infusion.
Interventions
DRUGOcrelizumab
Ocrelizumab will be administered as IV infusion.
PROCEDURELumbar Puncture
Participants will receive LP as specified in individual arms. Lumbar puncture is optional at week 52, except for RMS Cohort Arm 3 and PPMS Cohort. In addition, the lumbar punctures in the Long Term Extension phase is every other year.
DRUGMethyloprednisolone
Participants will receive 100 mg of IV methylprenisolone (or an equivalent) prior to ocrelizumab infusion.
DRUGAntihistamine
Participants will receive an antihistamine, such as diphenhydramine, prior to ocrelizumab infusion.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria: * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \<1 percent (%) per year during the treatment period and for at least 24 weeks after the last dose of study treatment or until their B-cells have repleted, whichever is longer Inclusion Criteria Specific to RMS Participants: * Diagnosis of RMS in accordance with the 2010 revised McDonald criteria * Expanded Disability Status Scale (EDSS) score of 0 to 5.5 points, inclusive, at Screening * Disease duration from the onset of multiple sclerosis symptoms less than (\<) 15 years in participants with an EDSS score greater than (\>) 5.0 at Screening * Either treatment-naive or receiving treatment with disease-modifying therapies, including prior use of interferon (IFN)-beta-1a (Avonex®, Rebif®), IFN-beta-1b (Betaseron®/Betaferon), or glatiramer acetate (Copaxone®). * At least one clinically documented relapse in the past year and/or at least one T1-weighted Gadolinium (Gd)-enhancing lesion in the past year and/or at least one new T2 lesion in the past year at the time of enrollment Inclusion Criteria Specific to RMS Cohort Arm 4 Participants: * Must meet inclusion criteria for the RMS cohort * Separate signed Informed Consent Form for the RMS Delayed Time to Start Control Arm (Arm 4) * Must be willing to remain on the same dose and regimen of current standard of care, or no treatment if treatment-naïve, for 12 weeks after study enrollment The treating and/or study physician must agree that the participant is eligible to remain on the same dose and regimen of their current standard of care at Screening, or to receive no treatment if the participant is treatment-naïve, for 12 weeks after study enrollment Inclusion Criteria Specific to PPMS Participants: * Diagnosis of PPMS in accordance with the 2010 revised McDonald criteria * EDSS score of 3.0 - 6.5 points, inclusive, at Screening * Disease duration from the onset of multiple sclerosis symptoms \<10 years in participants with an EDSS at Screening less than or equal to (\</=) 5.0 * Documented history of either elevated immunoglobulin G (IgG) Index or one or more IgG oligoclonal bands (OCBs) detected by isoelectric focusing
Exclusion criteria
* Diagnosis of secondary progressive multiple sclerosis without relapses for at least 1 year * History or known presence of recurrent or chronic infection (e.g., human immunodeficiency virus \[HIV\], syphilis, tuberculosis) * History of recurrent aspiration pneumonia requiring antibiotic therapy * History of cancer, including solid tumors and hematological malignancies (except basal cell, in situ squamous cell carcinomas of the skin, and in situ carcinoma of the cervix of the uterus that have been excised and resolved with documented clean margins on pathology) * History of or currently active primary or secondary immunodeficiency * History of coagulation disorders * History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies * History of alcohol or other drug abuse within 24 weeks prior to enrollment * Known presence or history of other neurologic disorders Significant, uncontrolled disease, such as cardiovascular (including cardiac arrhythmia), pulmonary (including chronic obstructive pulmonary disease), renal, hepatic, endocrine, gastrointestinal, or any other significant disease * Congestive heart failure (according to New York Heart Association III or IV functional severity) * Known active bacterial, viral, fungal, mycobacterial infection, or any major episode of infection requiring hospitalization or treatment with IV antibiotics * Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study * Contraindications or intolerance to oral or IV corticosteroids, including IV methylprednisolone, according to the country label * Contraindication for LP * Previous treatment with B cell-targeted therapies (such as rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab) * Previous treatment with natalizumab/Tysabri®, alemtuzumab, anti-CD4 agents, cladribine, teriflunomide, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation * Treatment with fingolimod/Gilenya®, dimethyl fumarate/Tecfidera®, or similar treatment within 6 months prior to enrollment * Receipt of a live vaccine within 6 weeks prior to enrollment * Systemic corticosteroid therapy within 4 weeks prior to Baseline * Previous or concurrent treatment with any investigational agent or treatment with any experimental procedure for multiple sclerosis (such as treatment for chronic cerebrospinal venous insufficiency) * Certain laboratory abnormalities or findings at Screening * Inability to complete an MRI * Lack of peripheral venous access * Pregnant or lactating, or intending to become pregnant during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | From Baseline to post-treatment (Week 12, 24, 52 according to randomization and Weeks 144 and 240) | Primary Analysis was based on following data-cut off: Arm 1: Baseline to post-treatment at 12 weeks Arm 2: Baseline to post-treatment at 24 weeks Arm 3: Baseline to post-treatment at 52 weeks Arm 4: Baseline to post-treatment at 12 weeks PPMS Cohort: Baseline to post-treatment at 52 weeks |
| Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | From Baseline to post-treatment (Week 12, 24, 52 according to randomization and Weeks 144 and 240) | Arm 1: Baseline to post-treatment at 12 weeks Arm 2: Baseline to post-treatment at 24 weeks Arm 3: Baseline to post-treatment at 52 weeks Arm 4: Baseline to post-treatment at 12 weeks PPMS Cohort: Baseline to post-treatment at 52 weeks |
| Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab | From Baseline to post-treatment (Week 12, 24, 52 according to randomization and Weeks 144 and 240) | Arm 1: Baseline to post-treatment at 12 weeks Arm 2: Baseline to post-treatment at 24 weeks Arm 3: Baseline to post-treatment at 52 weeks Arm 4: Baseline to post-treatment at 12 weeks PPMS Cohort: Baseline to post-treatment at 52 weeks |
Countries
Canada, Germany, Sweden, United States
Participant flow
Recruitment details
131 patients enrolled at 17 study locations in the U.S., Canada, Germany, and Sweden
Participants by arm
| Arm | Count |
|---|---|
| RMS Cohort Arm 1: Ocrelizumab + LP Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 12. Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72. | 23 |
| RMS Cohort Arm 2: Ocrelizumab + LP Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 24. Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72. | 31 |
| RMS Cohort Arm 3: Ocrelizumab + LP Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72. | 28 |
| RMS Cohort Arm 4: Ocrelizumab + LP Ocrelizumab treatment will be delayed for 12 weeks from pre-treatment baseline. Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP at Week -12 (pre-treatment baseline) and a second LP before the start of dosing (Week 1, treatment baseline). Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72. | 18 |
| PPMS Cohort: Ocrelizumab + LP For the PPMS cohort, ocrelizumab will be administered as two 300-mg IV infusions separated by 14 days at a scheduled interval of every 24 weeks during the treatment period and then as a single 600-mg dose every 24 weeks starting week 72 during the Long-Term Extension period. | 31 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 2 | 0 | 0 |
| Overall Study | Continued Onto Commercially Available Ocrelizumab | 12 | 12 | 14 | 14 | 21 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 | 1 | 1 |
| Overall Study | Non-Compliance With Study Drug | 1 | 3 | 1 | 0 | 1 |
| Overall Study | Other | 3 | 4 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 2 | 2 | 0 | 0 | 1 |
| Overall Study | Pregnancy | 0 | 0 | 2 | 1 | 0 |
| Overall Study | Study Terminated By Sponsor | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 8 | 7 | 1 | 4 |
Baseline characteristics
| Characteristic | RMS Cohort Arm 1: Ocrelizumab + LP | RMS Cohort Arm 2: Ocrelizumab + LP | RMS Cohort Arm 3: Ocrelizumab + LP | RMS Cohort Arm 4: Ocrelizumab + LP | PPMS Cohort: Ocrelizumab + LP | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 31 Participants | 28 Participants | 18 Participants | 31 Participants | 131 Participants |
| Age, Continuous | 36.0 Years STANDARD_DEVIATION 10.4 | 38.7 Years STANDARD_DEVIATION 10.4 | 34.6 Years STANDARD_DEVIATION 10.8 | 36.4 Years STANDARD_DEVIATION 9.8 | 44.9 Years STANDARD_DEVIATION 7.4 | 38.5 Years STANDARD_DEVIATION 10.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 28 Participants | 27 Participants | 17 Participants | 28 Participants | 122 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants | 3 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 21 Participants | 28 Participants | 25 Participants | 13 Participants | 29 Participants | 116 Participants |
| Sex/Gender, Customized Female | 15 Participants | 22 Participants | 20 Participants | 11 Participants | 15 Participants | 83 Participants |
| Sex/Gender, Customized Male | 8 Participants | 9 Participants | 8 Participants | 7 Participants | 16 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 23 | 0 / 31 | 0 / 28 | 0 / 18 | 1 / 31 |
| other Total, other adverse events | 23 / 23 | 28 / 31 | 27 / 28 | 17 / 18 | 31 / 31 |
| serious Total, serious adverse events | 5 / 23 | 5 / 31 | 1 / 28 | 5 / 18 | 9 / 31 |
Outcome results
Primary
Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab
Arm 1: Baseline to post-treatment at 12 weeks Arm 2: Baseline to post-treatment at 24 weeks Arm 3: Baseline to post-treatment at 52 weeks Arm 4: Baseline to post-treatment at 12 weeks PPMS Cohort: Baseline to post-treatment at 52 weeks
Time frame: From Baseline to post-treatment (Week 12, 24, 52 according to randomization and Weeks 144 and 240)
Population: The ITT population is defined as all patients enrolled in the study who received at least one dose of Ocrevus
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RMS Cohort Arm 1: Ocrelizumab + LP | Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab | Primary Analysis | -6.61 cells/μL | Standard Deviation 10.48 |
| RMS Cohort Arm 1: Ocrelizumab + LP | Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab | LTE phase Week 240 | -3.00 cells/μL | Standard Deviation 3.16 |
| RMS Cohort Arm 1: Ocrelizumab + LP | Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab | LTE phase Week 144 | -3.45 cells/μL | Standard Deviation 2.33 |
| RMS Cohort Arm 2: Ocrelizumab + LP | Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab | LTE phase Week 144 | 1.78 cells/μL | Standard Deviation 9.76 |
| RMS Cohort Arm 2: Ocrelizumab + LP | Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab | Primary Analysis | -1.92 cells/μL | Standard Deviation 3.15 |
| RMS Cohort Arm 2: Ocrelizumab + LP | Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab | LTE phase Week 240 | -3.47 cells/μL | Standard Deviation 2.31 |
| RMS Cohort Arm 3: Ocrelizumab + LP | Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab | LTE phase Week 144 | -0.83 cells/μL | Standard Deviation 4.64 |
| RMS Cohort Arm 3: Ocrelizumab + LP | Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab | Primary Analysis | -1.46 cells/μL | Standard Deviation 2.67 |
| RMS Cohort Arm 3: Ocrelizumab + LP | Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab | LTE phase Week 240 | -1.41 cells/μL | Standard Deviation 1.3 |
| RMS Cohort Arm 4: Ocrelizumab + LP | Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab | Primary Analysis | -1.98 cells/μL | Standard Deviation 5.1 |
| RMS Cohort Arm 4: Ocrelizumab + LP | Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab | LTE phase Week 240 | -1.67 cells/μL | Standard Deviation 2.42 |
| RMS Cohort Arm 4: Ocrelizumab + LP | Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab | LTE phase Week 144 | 2.25 cells/μL | Standard Deviation 0.17 |
| PPMS Cohort: Ocrelizumab + LP | Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab | LTE phase Week 144 | -3.62 cells/μL | Standard Deviation 5.56 |
| PPMS Cohort: Ocrelizumab + LP | Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab | Primary Analysis | -3.25 cells/μL | Standard Deviation 4.32 |
| PPMS Cohort: Ocrelizumab + LP | Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab | LTE phase Week 240 | -1.37 cells/μL | Standard Deviation 0.54 |
Primary
Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab
Primary Analysis was based on following data-cut off: Arm 1: Baseline to post-treatment at 12 weeks Arm 2: Baseline to post-treatment at 24 weeks Arm 3: Baseline to post-treatment at 52 weeks Arm 4: Baseline to post-treatment at 12 weeks PPMS Cohort: Baseline to post-treatment at 52 weeks
Time frame: From Baseline to post-treatment (Week 12, 24, 52 according to randomization and Weeks 144 and 240)
Population: The ITT population is defined as all patients enrolled in the study who received at least one dose of Ocrevus
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RMS Cohort Arm 1: Ocrelizumab + LP | Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | Primary Analysis | -1232.97 pg/mL | Standard Deviation 2060.37 |
| RMS Cohort Arm 1: Ocrelizumab + LP | Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 240 | -2499.98 pg/mL | Standard Deviation 3606.71 |
| RMS Cohort Arm 1: Ocrelizumab + LP | Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 144 | -2331.89 pg/mL | Standard Deviation 3334.8 |
| RMS Cohort Arm 2: Ocrelizumab + LP | Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 144 | -644.50 pg/mL | Standard Deviation 1371.39 |
| RMS Cohort Arm 2: Ocrelizumab + LP | Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | Primary Analysis | -1169.13 pg/mL | Standard Deviation 1739.49 |
| RMS Cohort Arm 2: Ocrelizumab + LP | Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 240 | -791.51 pg/mL | Standard Deviation 1150.89 |
| RMS Cohort Arm 3: Ocrelizumab + LP | Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 144 | -1287.58 pg/mL | Standard Deviation 1822.72 |
| RMS Cohort Arm 3: Ocrelizumab + LP | Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | Primary Analysis | -1008.13 pg/mL | Standard Deviation 1132.68 |
| RMS Cohort Arm 3: Ocrelizumab + LP | Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 240 | -1060.33 pg/mL | Standard Deviation 1678.95 |
| RMS Cohort Arm 4: Ocrelizumab + LP | Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | Primary Analysis | -931.83 pg/mL | Standard Deviation 2816.27 |
| RMS Cohort Arm 4: Ocrelizumab + LP | Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 240 | -5488.70 pg/mL | Standard Deviation 4350.46 |
| RMS Cohort Arm 4: Ocrelizumab + LP | Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 144 | -2544.33 pg/mL | Standard Deviation 3807.94 |
| PPMS Cohort: Ocrelizumab + LP | Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 144 | -925.32 pg/mL | Standard Deviation 2507.97 |
| PPMS Cohort: Ocrelizumab + LP | Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | Primary Analysis | 261.85 pg/mL | Standard Deviation 1175.72 |
| PPMS Cohort: Ocrelizumab + LP | Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 240 | -1221.33 pg/mL | Standard Deviation 2738.19 |
Primary
Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab
Arm 1: Baseline to post-treatment at 12 weeks Arm 2: Baseline to post-treatment at 24 weeks Arm 3: Baseline to post-treatment at 52 weeks Arm 4: Baseline to post-treatment at 12 weeks PPMS Cohort: Baseline to post-treatment at 52 weeks
Time frame: From Baseline to post-treatment (Week 12, 24, 52 according to randomization and Weeks 144 and 240)
Population: The ITT population is defined as all patients enrolled in the study who received at least one dose of Ocrevus
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RMS Cohort Arm 1: Ocrelizumab + LP | Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | Primary Analysis | -0.22 cells/μL | Standard Deviation 0.26 |
| RMS Cohort Arm 1: Ocrelizumab + LP | Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 240 | -0.08 cells/μL | Standard Deviation 0.09 |
| RMS Cohort Arm 1: Ocrelizumab + LP | Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 144 | -0.11 cells/μL | Standard Deviation 0.08 |
| RMS Cohort Arm 2: Ocrelizumab + LP | Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 144 | -0.14 cells/μL | Standard Deviation 0.2 |
| RMS Cohort Arm 2: Ocrelizumab + LP | Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | Primary Analysis | -0.15 cells/μL | Standard Deviation 0.36 |
| RMS Cohort Arm 2: Ocrelizumab + LP | Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 240 | -0.20 cells/μL | Standard Deviation 0.26 |
| RMS Cohort Arm 3: Ocrelizumab + LP | Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 144 | -0.06 cells/μL | Standard Deviation 0.23 |
| RMS Cohort Arm 3: Ocrelizumab + LP | Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | Primary Analysis | -0.13 cells/μL | Standard Deviation 0.32 |
| RMS Cohort Arm 3: Ocrelizumab + LP | Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 240 | -0.02 cells/μL | Standard Deviation 0.01 |
| RMS Cohort Arm 4: Ocrelizumab + LP | Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | Primary Analysis | -0.18 cells/μL | Standard Deviation 0.37 |
| RMS Cohort Arm 4: Ocrelizumab + LP | Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 240 | -0.04 cells/μL | Standard Deviation 0.05 |
| RMS Cohort Arm 4: Ocrelizumab + LP | Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 144 | 0.15 cells/μL | Standard Deviation 0.1 |
| PPMS Cohort: Ocrelizumab + LP | Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 144 | -0.01 cells/μL | Standard Deviation 0.09 |
| PPMS Cohort: Ocrelizumab + LP | Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | Primary Analysis | -0.09 cells/μL | Standard Deviation 0.11 |
| PPMS Cohort: Ocrelizumab + LP | Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab | LTE phase Week 240 | 0.01 cells/μL | Standard Deviation 0.03 |