Primary Progressive Multiple Sclerosis, Relapsing Multiple Sclerosis
Conditions
Brief summary
The main purpose of this study is to evaluate the efficacy of ocrelizumab in participants with relapsing multiple sclerosis (RMS) and to characterize the ocrelizumab pharmacodynamic (PD) profile in Chinese participants with primary progressive multiple sclerosis (PPMS).
Interventions
DRUGOcrelizumab
Ocrelizumab will be administered as per the schedule specified in the respective arms.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of RMS/PPMS in accordance with the revised 2017 McDonald Criteria * EDSS score from 0-5.5 (RMS) or 3.0-6.5 (PPMS), inclusive, at screening and baseline * Documented MRI of brain with abnormalities consistent with MS before screening
Exclusion criteria
* Diagnosis of PPMS or non-active secondary progressive multiple sclerosis (SPMS) (only for RMS cohort) * History of relapsing remitting multiple sclerosis (RRMS) or SPMS at screening (only for PPMS cohort) * Disease duration of more than 10 years in participants with an EDSS ≤ 2.0 at screening (only for RMS cohort) * History of confirmed or suspected progressive multifocal leukoencephalopathy (PML) * Inability to complete an MRI scan or contraindication to Gd administration * Contraindications to mandatory pre-medications (i.e., corticosteroids and antihistamines) * Known presence of other neurologic disorders if they 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 * Known history of human immunodeficiency virus (HIV) infection * Lack of peripheral venous access * Previous treatment with B-cell targeted therapies (i.e., rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab), unless the last infusion was at least 6 months prior to screening * Positive screening tests for hepatitis B virus (HBV) and/or hepatitis C virus (HCV)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| RMS Cohort: Annualized Protocol-defined Relapse Rate | Up to approximately 1.6 years |
| PPMS Cohort: B-cell Levels in Blood | Up to Week 48 |
| PPMS Cohort: Percentage of Participants Achieving Cluster of Differentiation 19 (CD19+) B-cell Levels of <10 Cells/Microliter (μL) at Week 48 | At Week 48 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RMS Cohort: Percentage of Participants Who Have No Evidence of Disease Activity (NEDA3) During a 48-week Period | Up to Week 48 | — |
| RMS Cohort: Percentage of Relapse-free Participants by Week 48 | Up to Week 48 | — |
| RMS Cohort: Percentage of Participants Who Have NEDA3 During a 24-week Period | Up to Week 24 | — |
| RMS Cohort: Total Number of T1 Gadolinium (Gd)-enhancing Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) | Up to Week 48 | — |
| RMS Cohort: Total Number of New or Enlarging T2 Hyperintense Lesions as Detected by Brain MRI | Up to Week 48 | — |
| RMS and PPMS Cohorts: Change From Baseline to Week 48 in the Concentration of Serum Neurofilament Light Chain (Nfl) | Baseline up to Week 48 | — |
| RMS and PPMS Cohorts: Change From Baseline to Week 48 in Expanded Disability Status Scale (EDSS) | Baseline up to Week 48 | EDSS is a scale for assessing neurologic impairment in participants with multiple sclerosis (MS). 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 functional systems scores (FSS), and ambulation, which is scored as ambulation score. Each FSS is an ordinal clinical rating scale ranging from 0 to 5 or 6 and an ambulation score that is rated from 0 to 16. These ratings are then used in conjunction with observations, as well as information, concerning ambulation and use of assistive devices to determine the total EDSS score. Values are from 0 points (normal neurological examination) up to 10 points (death), increasing in increments of 0.5 points. Higher scores represent increased disability. |
| RMS and PPMS Cohorts: Change From Baseline to Week 48 in Timed 25-Foot Walk Test (T25FWT) | Baseline up to Week 48 | The T25FWT test is a performance measure used to assess walking speed based on a timed 25-foot walk. The participant is directed to start at one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly and safely as possible and immediately walk back the same distance. Score for the T25FWT is the average of the two completed trials. The time taken to complete the test is measured in seconds. The longer it takes to walk, higher the score, which indicates deterioration and greater impairment. Lower times indicate better performance and greater mobility. A 20% change from baseline of the averaged T25FWT is typically considered clinically meaningful. |
| RMS and PPMS Cohorts: Change From Baseline to Week 48 in 9-Hole Peg Test (9-HPT) | Baseline up to Week 48 | The 9-HPT is a performance measure used to assess upper extremity (arm and hand) function. Participants are instructed to place pegs one by one into each of nine holes arranged in a board stabilized with a plastic nonslip sheet on a solid table, and then to remove these pegs from the holes. Both the dominant and non-dominant hands are tested twice (two consecutive trials for each hand). The participants are required to complete two successful trials for each hand. The amount of time (in seconds) required to place and remove all nine pegs is recorded for each trial. More time indicates higher raw scores, which indicates deterioration. A 20% change from baseline is typically considered clinically meaningful. |
| RMS and PPMS Cohorts: Change From Baseline in EuroQoL 5-Dimension Questionnaire (5-Level Version; EQ-5D-5L) Index Score at Week 48 | Baseline, Week 48 | The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. |
| RMS and PPMS Cohorts: Serum Concentration of Ocrelizumab | Up to Week 48 | — |
| RMS Cohort: B-cell Levels in Blood | Up to Week 48 | — |
| RMS Cohort: Percentage of Participants Achieving CD19+ B-cell Levels of <10 cells/μL at Week 48 | At Week 48 | — |
| PPMS Cohort: Total Number of T1 Gd-enhancing Lesions as Detected by Brain MRI at Week 24 and Week 48 | Week 24 and Week 48 | — |
| PPMS Cohort: Total Number of New or Enlarging T2 Hyperintense Lesions as Detected by Brain MRI at Week 24 and Week 48 | Week 24 and Week 48 | — |
| RMS and PPMS Cohorts: Number of Participants With Adverse Events (AEs) | Up to approximately 1.8 years | — |
| RMS and PPMS Cohorts: Change from Baseline in T-cell Level | Up to approximately 1.8 years | — |
| RMS and PPMS Cohorts: Percentage of Participants With Suicidal Ideation or Behaviour, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Up to approximately 1.8 years | C-SSRS is an assessment tool used to assess lifetime suicidality of participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, and attempts with actual/potential lethality. Categories have binary responses (yes/no) and include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior is indicated by a "yes" answer to any of the listed categories. Score of 0 is assigned if no suicide risk is present. Score of 1 or higher indicate suicidal ideation or behavior. |
Countries
China
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed