Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Ocrelizumab Test Formulation
Ocrelizumab · 12 trials · 10 indications
The population-level summary is rate ratio of ARR. The ARR is calculated as the total number of protocol-defined relapses divided by the total patient-years. Protocol-defined relapse is the occurrence of new/worsening neurological symptoms attributable to multiple sclerosis (MS) and immediately preceded by relatively stable or improving neurological state for ≥ 30 days. Symptoms must persist for \>24 hours \& should not be attributable to confounding clinical factors. The new/worsening neurological symptoms must be accompanied by objective neurological worsening consistent with an increase of at least half a step on the expanded disability status scale (EDSS) score, or 2 points on one of the appropriate functional system (FS) scores, or 1 point on two or more of the appropriate FS scores. The change must affect the selected FS (i.e., pyramidal, ambulation, cerebellar, brainstem, sensory, or visual). Adjusted values were reported. OM assessed non inferiority of ocrelizumab vs fingolimod.
Time to onset of cCDP12=time from randomization to the first occurrence of at least one of the following progression events: 1) 20% worsening from baseline in 9-hole Peg Test (9-HPT) confirmed for at least 12 weeks; 2) increase of ≥ 1.0 point from baseline in Expanded Disability Status Scale (EDSS) score in participants with a baseline EDSS score ≤5.5 or an increase of ≥ 0.5 point in participants with a baseline EDSS score of \>5.5 that is confirmed for at least 12 weeks. EDSS disability scale is based on a standard neurological examination, incorporating functional systems \& ambulation, that ranges in 0.5-point steps from 0 \[normal\] to 10.0 \[death\]. 9-HPT is a quantitative measure of arm \& hand function, where participants placed \& removed pegs 1 by 1 into 9 holes arranged in a board \& complete 2 successful trials for each hand \& the total time (in seconds) required was recorded. The longer it took to complete the test, the higher the scores, indicating deterioration.
Time to onset of cCDP12 was defined as the time from randomization to the first occurrence of at least one of the following progression events: 1) 20% worsening from baseline in 9-HPT confirmed for at least 12 weeks; 2) increase of ≥ 1.0 point from baseline in EDSS score in participants with a baseline EDSS score ≤5.5 or an increase of ≥ 0.5 point in participants with a baseline EDSS score of \>5.5 that is confirmed for at least 12 weeks. EDSS disability scale is based on a standard neurological examination, incorporating functional systems \& ambulation, that ranges in 0.5-point steps from 0 \[normal\] to 10.0 \[death\]. 9-HPT is a quantitative measure of arm \& hand function, where participants placed \& removed pegs 1 by 1 into 9 holes arranged in a board \& complete 2 successful trials for each hand \& the total time (in seconds) required was recorded. The longer it took to complete the test, the higher the scores, indicating deterioration.
NEP is defined as no progression sustained for at least 24 weeks on all of the following three components (confirmed disability progression \[CDP\]; ≥20% increase in timed 25-foot walk test \[T25FWT\]; ≥20% increase in nine-hole peg test \[9HPT\])
NEPAD is defined as no progression sustained for at least 24 weeks on all of the three components of NEP (CDP, T25FWT, 9HPT), no protocol-defined relapse, no enlarging or new T2 lesion, and no T1 gadolinium (Gd+)-enhancing lesion
A protocol-defined event of disease activity was defined by the occurrence of at least one of the following while on treatment with ocrelizumab: * A protocol-defined relapse (PDR) * 24-week CDP based on increase in EDSS while on treatment with ocrelizumab * A T1 Gd-enhanced lesion after Week 8 * A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan
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
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
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
Protocol-defined event is the occurrence of either protocol-defined relapse (occurrence of new or worsening neurological symptoms attributable to multiple sclerosis) or T1 gadolinium (Gd)-enhanced lesion on brain magnetic resonance imaging (MRI) or new and/or enlarging T2 lesion on brain MRI or confirmed disability progression at 24 weeks.
Rate and frequency of Grade 3 or 4 IRRs with onset on or after the shorter ocrelizumab infusion
The time to onset of CDP was defined as time from baseline to first disability progression, which is confirmed at next regularly scheduled visit \>=12 weeks (\>=84 days) after initial disability progression. Baseline for time to onset of CDP is the date of randomization, independent of the first day of dosing. Disability progression is defined as an increase of \>= 1.0 point from baseline expanded disability status scale (EDSS) score, if baseline EDSS value is \<=5.5 points (inclusive), or an increase of \>=0.5 points, if baseline EDSS is \>5.5 points. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). The randomized participants who did not receive any treatment were censored at days 0 in each Arm.
Mean of total number of gadolinium-enhancing T1 lesions observed on MRI scans of the brain at Weeks 12, 16, 20, 24 was determined using average imputation method.
| Arm | Type | Description |
|---|---|---|
| Ocrelizumab | EXPERIMENTAL | Participants will receive ocrelizumab, as IV infusion Q24W. The first dose is given as dual infusions of half the dose of ocrelizumab on Days 1 and 15, and subsequent doses are given as single infusions of ocrelizumab Q24W. Participants will also receive a placebo of fingolimod administered as QD capsule. |
| Fingolimod | ACTIVE_COMPARATOR | Participants will receive fingolimod PO, QD as per the prescribing information provided with fingolimod. Participants will also receive a placebo of ocrelizumab administered as IV infusion on Days 1 and 15, and Q24W thereafter. |
| Ocrelizumab: Intravenous (IV) formulation | ACTIVE_COMPARATOR | Participants will receive the first dose of ocrelizumab IV as two IV infusions given 14 days apart. The subsequent doses of study drug will be administered as SC injections. A minimum of 22 weeks should be kept between SC doses. Participants will undergo 96 weeks of study treatment. |
| Ocrelizumab: Subcutaneous (SC) formulation | EXPERIMENTAL | Participants will receive the first dose of ocrelizumab SC as one SC injection at a dose which is expected to result in non-inferior exposure to ocrelizumab IV. The subsequent doses of study drug will be administered as SC injections. A minimum of 22 weeks should be kept between the first and second SC doses, and between subsequent SC doses. Participants will undergo 96 weeks of study treatment. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive placebo matched to ocrelizumab by IV infusion every 24 weeks. |
| RMS Cohort Arm 1: Ocrelizumab + LP | EXPERIMENTAL | 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. |
| RMS Cohort Arm 2: Ocrelizumab + LP | EXPERIMENTAL | 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. |
| RMS Cohort Arm 3: Ocrelizumab + LP | EXPERIMENTAL | 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. |
| RMS Cohort Arm 4: Ocrelizumab + LP | EXPERIMENTAL | 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. |
| PPMS Cohort: Ocrelizumab + LP | EXPERIMENTAL | 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. |
| Ocrelizumab (substudy) | EXPERIMENTAL | Participants with no serious IRR throughout the main study will be eligible to enroll in an optional substudy and receive one additional shorter infusion of ocrelizumab at the Week 96 visit. Ocrelizumab will be administered IV as a single 600-mg dose at a shorter infusion rate (approximately 2 hours instead of 3.5 hours) |
| Ocrelizumab 600 mg | PLACEBO_COMPARATOR | Participants with PPMS received ocrelizumab as two IV infusions of 300 mg separated by 14 days at a scheduled interval of every 24 weeks up to at least 120 weeks. |
| Ocrelizumab 1000 mg | EXPERIMENTAL | Participants received two IV infusions of ocrelizumab 1000 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 1000 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 1000 mg was administered on Day 1 of Cycle 3 and a single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycle 4. Each cycle was of 168 days. |
| Avonex | ACTIVE_COMPARATOR | Participants received weekly intramuscular injections of Avonex 30 microgram (mcg) in Cycle 1, followed by two infusions of OCR 300 mg separated by 14 days in Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days. |
| Group A: Cohorts A1-A4 | EXPERIMENTAL | Participants (participants pretreated with ocrelizumab) will receive a single injection of subcutaneous (SC) ocrelizumab co-mixed with rHuPH20 in the abdomen. For every new dose level, recruitment will be staggered by enrolling 1 participant in each cohort followed by a 48-hour waiting period to review safety and tolerability data by the Safety Monitoring Committee (SMC) prior to enrolling subsequent participants in the same cohort. Currently, the planned dose escalation steps for patients who enroll in Group A are as follows: * Cohort A1: 40 mg of SC ocrelizumab * Cohort A2: 200 mg of SC ocrelizumab * Cohort A3: 600 mg of SC ocrelizumab * Cohort A4: 1200 mg of SC ocrelizumab |
| Group A: Cohort A5 | EXPERIMENTAL | In the non-randomized subphase, participants will receive a single SC injection of ocrelizumab co-mixed with rHuPH20 in the abdomen. |
| Group A: Cohort AA | EXPERIMENTAL | Participants will receive a single 600-mg dose ocrelizumab by intravenous (IV) infusion |
| Group B: Cohorts B1-B4 | EXPERIMENTAL | Ocrelizumab treatment- naive participants will receive a minimum of 3 patients in Cohort B will receive a single SC injection of ocrelizumab co-mixed with rHuPH20 in the abdomen. * Cohort B1: 40 mg of SC ocrelizumab * Cohort B2: 200 mg of SC ocrelizumab * Cohort B3: 600 mg of SC ocrelizumab * Cohort B4: 1200 mg of SC ocrelizumab |
| Cohort A: Ocrelizumab 200 mg/m^2 | EXPERIMENTAL | Participants will receive a total of 8 infusions of ocrelizumab 200 milligram per square meter (mg/m\^2) given at intervals of 3 weeks, until disease progression or unacceptable toxicity. |
| Cohort B: Ocrelizumab 375 mg/m^2 | EXPERIMENTAL | Participants will receive a total of 8 infusions of ocrelizumab 375 mg/m\^2 given at intervals of 3 weeks, until disease progression or unacceptable toxicity. |
| Cohort C: Ocrelizumab 375/750 mg/m^2 | EXPERIMENTAL | Participants will receive first infusion of ocrelizumab 375 mg/m\^2 followed by 7 infusions of 750 mg/m\^2 given at intervals of 3 weeks, until disease progression or unacceptable toxicity. |
| Name | Type | Description |
|---|---|---|
| Ocrelizumab | DRUG | Ocrelizumab, 300 milligrams (mg) will be administered as IV infusion to participants who weigh \< 35 kilograms (kg), and ocrelizumab 600 mg, IV will be administered to participants who weigh ≥ 35 kg on Days 1 and 15 (half the dose, 2 weeks apart), and Q24W thereafter. |
| Ocrelizumab Placebo | OTHER | Ocrelizumab matching placebo will be administered as IV infusion on Day 1 and Day 15, and Q24W thereafter. |
| Fingolimod | DRUG | Fingolimod will be administered QD as a capsule per the prescribing information (0.25 mg to participants who weigh ≤ 40 kg and 0.5 mg to participants who weigh \> 40 kg). |
| Fingolimod Placebo | OTHER | Fingolimod matching placebo will be administered QD as a capsule. |
| Ocrelizumab IV | DRUG | IV Injection |
| Ocrelizumab SC | DRUG | SC Injection |
| Methylprednisolone IV | DRUG | Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab infusion |
| Diphenhydramine IV | DRUG | Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab infusion |
| Dexamethasone given orally | DRUG | Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab injection |
| Desloratadine given orally | DRUG | Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab injection |
| Placebo | DRUG | The first dose of placebo will be administered as two IV infusions given 14 days apart. For the subsequent doses, placebo will be administered as a single infusion every 24 weeks, with a minimum interval of 20 or 22 weeks, depending on if the previous dose was administered in one or two infusions, maintained between each infusion. |
| Lumbar Puncture | PROCEDURE | 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. |
| Methyloprednisolone | DRUG | Participants will receive 100 mg of IV methylprenisolone (or an equivalent) prior to ocrelizumab infusion. |
| Antihistamine | DRUG | Participants will receive an antihistamine, such as diphenhydramine, prior to ocrelizumab infusion. |
| Avonex | DRUG | Avonex was administered weekly intramuscular injections of 30 mcg in cycle 1 Day 1. |
| rHuPH20 | DRUG | Administered in a 2-mL glass vial as a sterile, single-use, injectable liquid to be manually mixed with SC ocrelizumab |
Inclusion Criteria: * Body weight ≥ 25 kg * Diagnosis of RRMS in accordance with the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for pediatric multiple sclerosis (MS), Version 2012, or McDonald criteria 2017 * Expanded Disability Status Scale (EDSS) at screening: 0-5.5,...
Ocrelizumab is an investigational drug being studied for multiple sclerosis (MS), including relapsing multiple sclerosis, relapsing-remitting multiple sclerosis, and progressive multiple sclerosis. It is also being evaluated in a Phase 1 trial for follicular non-Hodgkin's lymphoma. The drug is in clinical development and is not yet approved.
Ocrelizumab is a monoclonal antibody, indicated by its -mab suffix. It is designed to target CD20-positive B cells, which are involved in the immune response. By binding to these cells, it aims to modulate the immune system's attack on the nervous system in multiple sclerosis.
Ocrelizumab is developed by Roche Holding AG, which trades under the ticker RHHBY. Roche is conducting clinical trials to evaluate the drug's safety and efficacy in multiple sclerosis and other conditions.
Ocrelizumab is in Phase 1 clinical development. While some completed trials were Phase 3, the drug is not approved and remains investigational. It is being studied for multiple sclerosis indications, with active trials ongoing.
Ocrelizumab has been studied in several trials, including NCT02688985 (Phase 3, completed, in relapsing and primary progressive MS), NCT02723071 (Phase 1, completed, in follicular non-Hodgkin's lymphoma), NCT03523858 (Phase 3, active, in progressive MS), and NCT03972306 (Phase 1, completed, for subcutaneous administration in MS).
Yes, Ocrelizumab is also known as Ocrelizumab Test Formulation. This alternative name may be used in certain research or testing contexts, but it refers to the same drug being developed by Roche for multiple sclerosis.