Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Ocrelizumab
Ocrelizumab Test Formulation · 8 trials · 1 indication
PROMISnq PFMS-15a includes 15 items that evaluate the impact of MS on a participant's physical functioning, including mobility, upper limb function and activities of daily living. Nine items assess the degree of difficulty in completing physical activities using a 5-point verbal rating scale ranging from 5="without any difficulty" to 1="unable to do". Four items assess physical function limitations, rated from 5="not at all" to 1="cannot do". Two items assess the amount of difficulty associated with selected physical activities, rated from 5="no difficulty" to 1="can't do". Scores are reported as a standardized T-score metric, with higher scores reflecting better physical functioning.
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.
This outcome measure evaluates the occurrence of severe infusion-related reaction (IRR) with ocrelizumab 600 mg intravenously (IV) administered over the course of 2 hours. Rate and frequency of NCI CTCAE v4.0 Grade 3 and 4 IRRs
Improved, stable or worsened disability is measured by expanded disability status scale (EDSS) (annually/by epoch and over duration of the study) Stable EDSS is defined as EDSS change +/- 0.5. Worsening is \> 0.5 increase of EDSS, Improvement is \>0.5 decrease of EDSS
Time to 20% increase in timed nine-hole peg test (9HPT) sustained for at least 24 weeks and for at least 48 weeks, and proportion of patients achieving a sustained increase assessed yearly and at the end treatment
The population PK model was used to simulate concentration-time course and predict individual area under the concentration versus time curve. The data for the PK parameter: area under the concentration versus time curve was collected and analyzed as per body weight range (\<40kg to ≥40 kg).
The population PK model was used to simulate concentration-time course and predict individual Cmax. The data for the PK parameter: Cmax was collected and analyzed as per body weight range (\<40kg to ≥40 kg).
| Arm | Type | Description |
|---|---|---|
| Ocrelizumab | EXPERIMENTAL | Participants will receive ocrelizumab at the currently approved dose of 600 mg, IV infusion or 920 mg, SC injection as per the schedule in the parent study until access to the treatment becomes locally available, unacceptable safety concern, death or withdrawal of consent. |
| Ocrelizumab Higher Dose | EXPERIMENTAL | Participants will be randomized to receive a minimum of 5 higher treatment doses based on their body weight at baseline: 1200 mg (participant's body weight \<75 kilograms \[kg\]) or 1800 mg (participant's body weight ≥ 75 kg) of ocrelizumab administered by IV infusion Q24W in the DBT phase. 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). Mandatory methylprednisolone (or equivalent) and antihistaminic drug (e.g., diphenhydramine or equivalent) will be administered approximately 30-60 minutes prior to the start of each ocrelizumab infusion. |
| Ocrelizumab Approved Dose | ACTIVE_COMPARATOR | Participants will be randomized to receive a minimum of 5 treatment doses of 600 mg ocrelizumab administered by IV infusion Q24W in the DBT phase. During the optional OLE phase, participants will be offered a higher dose of ocrelizumab (either 1200 or 1800 mg), based on their body weight at OLE baseline, for approximately 96 weeks (4 doses in total). Mandatory methylprednisolone (or equivalent) and antihistaminic drug (e.g., diphenhydramine or equivalent) will be administered approximately 30-60 minutes prior to the start of each ocrelizumab infusion. |
| Cohort 1 | EXPERIMENTAL | This cohort will examine the effect of administering ocrelizumab per a shorter infusion protocol for Dose 2 or Dose 3. Participants who have already received one or two doses of ocrelizumab according to the approved infusion protocol and have reported no serious infusion-related reactions (IRRs) will be enrolled. They will then receive the next infusion of ocrelizumab (Dose 2 or Dose 3) at a dosage of 600 milligram (mg) over the course of approximately 2 hours. Dose 2 is administered at Week 24, Dose 3 is administered at Week 48 after initial infusion. |
| Cohort 2 | EXPERIMENTAL | This cohort will examine the effect of administering ocrelizumab per a shorter infusion protocol for the second infusion of Dose 1. Ocrelizumab-naïve participants will be enrolled who, after receiving Dose 1 of ocrelizumab at the approved rate have no reported serious IRRs, will then receive the second 300-mg shorter infusion over approximately 1.5 hours. |
| Ocrelizumab Test Formulation | EXPERIMENTAL | Participants will receive ocrelizumab test formulation, as SC injection, as per a pre-defined dosing regimen during the controlled phase and continuation phase. |
| Ocrelizumab Reference Formulation | ACTIVE_COMPARATOR | Participants will receive ocrelizumab reference formulation, 920 mg, as SC injection, on Day 1 during the controlled phase. Thereafter, participants will receive ocrelizumab test formulation, as SC injection, as per a pre-defined dosing regimen during the continuation phase. |
| Cohort 3 (optional) | EXPERIMENTAL | Based on PK, PD, safety, and tolerability data analyses of Cohorts 1 and 2, additional participants with a body weight from \>/= 25 kg to \< 40 kg may be enrolled and receive another dose level of ocrelizumab |
| Cohort 4 (optional) | EXPERIMENTAL | Based on PK, PD, safety, and tolerability data analyses of Cohorts 1 and 2, additional participants with a body weight \>/= 40 kg may be enrolled and receive another dose level of ocrelizumab |
| Name | Type | Description |
|---|---|---|
| Ocrelizumab | DRUG | Ocrelizumab will be administered at the approved dose of 600 mg, IV infusion or 920 mg, SC injection, according to the regimen in the parent study. |
| 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. |
| Methylprednisolone | DRUG | Premedication with 100 mg of methylprednisolone (or equivalent) will be administered by IV infusion prior to each ocrelizumab infusion. |
| Ocrelizumab Dose 1 | DRUG | 300 mg infusion administered to ocrelizumab-naive participants per approved protocol (over approximately 2.5 hours or longer) as per standard of care followed by a second 300 mg shorter infusion over approximately 1.5 hours. |
| Ocrelizumab Dose 2 and Dose 3 | DRUG | 600 mg infusion of ocrelizumab administered at a shorter rate (i.e. over the course of approximately 2 hours) at Week 24 and at Week 48 |
| Ocrelizumab Test Formulation | DRUG | Ocrelizumab test formulation will be administered as per the schedule specified in the respective arm. |
| Ocrelizumab Reference Formulation | DRUG | Ocrelizumab reference formulation will be administered as per the schedule specified in the respective arm. |
Inclusion Criteria: * Participants who were on ongoing ocrelizumab treatment on one of the following parent-studies \[Studies MN39159/CONSONANCE (NCT03523858), BN42082/MUSETTE (NCT04544436), BN42083/GAVOTTE (NCT04548999), BN44083/GLOBEAM, MN43978/CONSONANCE Ext., WA40404/O'HAND (NCT04035005), MN439...
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.