Multiple Sclerosis
Conditions
Brief summary
This study is an open-label, non-randomized study to evaluate rate and severity of infusion-related reactions (IRRs) of ocrelizumab infused over a shorter time period than the approved administration rate in participants with PPMS or RMS in the United States (U.S.). Participants will be enrolled into two cohorts. Cohort 1 will examine the effect of administering ocrelizumab per a shorter infusion protocol for Dose 2 or Dose 3. This cohort will consist of patients who have already received one or two doses of ocrelizumab according to the approved infusion protocol (i.e., per the currently U.S. label) and have reported no serious IRRs and who will then receive the next infusion of ocrelizumab at a higher rate in order to deliver 600 mg over the course of approximately 2 hours. Cohort 2 will examine the effect of administering ocrelizumab per a shorter infusion protocol for the second infusion of Dose 1. This cohort will consist of ocrelizumab naïve patients who, after receiving Infusion 1/Dose 1 of ocrelizumab at the approved rate (300 mg over approximately 2.5 hours or longer) have no reported serious IRRs, will then receive the second 300-mg shorter infusion over approximately 1.5 hours.
Interventions
DRUGOcrelizumab Dose 1
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.
DRUGOcrelizumab Dose 2 and Dose 3
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
Sponsors
Genentech, Inc.
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
* Eligible to receive ocrelizumab per the United States Package Insert (USPI) * Able to comply with the study protocol, in the investigator's judgment * Age 18-55 years, inclusive * Have a diagnosis of PPMS or RMS, confirmed per the revised 2017 McDonald criteria * Expanded Disability Status Scale (EDSS) score of 0 to 6.5, inclusive * 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% per year during the treatment period and for at least 6 months after the last dose of study treatment (per the USPI)
Exclusion criteria
* Experienced serious IRR(s) * History of life-threatening infusion reaction to ocrelizumab * Known presence of other neurological disorders * Pregnancy or lactation, or intention to become pregnant during the study * Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study * Significant, uncontrolled disease, such as cardiovascular (including cardiac arrhythmia), pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine, and gastrointestinal or any other significant disease that may preclude patient from participating in the study * Congestive heart failure * Known active bacterial, viral, fungal, mycobacterial infection or other infection or any severe episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to baseline visit or oral antibiotics within 2 weeks prior to baseline visit * History of or currently active primary or secondary immunodeficiency * History or known presence of recurrent or chronic infection (e.g., HIV, syphilis, tuberculosis) * History of recurrent aspiration pneumonia requiring antibiotic therapy * History of malignancy, including solid tumors and hematological malignancies,except basal cell, in situ squamous cell carcinoma of the skin, and in situ carcinoma of the cervix of the uterus that have been excised with clear margins * History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies * History of alcohol or drug abuse within 24 weeks prior to enrollment * Receipt of a live vaccine within 6 weeks prior to enrollment * Systemic corticosteroid therapy within 4 weeks prior to enrollment * Contraindications to or intolerance of oral or IV corticosteroids, including IV methylprednisolone (or equivalent steroid) administered according to the country label * Treatment with alemtuzumab * Treatment with a B-cell targeted therapies other than ocrelizumab * Treatment with a drug that is experimental * Abnormal laboratory results per local laboratory standards and investigator assessment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Infusion-related Reaction (IRR) Treated With 600 mg IV Ocrelizumab | During or within 24 hours of administration | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With IRRs | During or within 24 hours of administration | This outcome measure evaluates the occurrence of overall IRRs with ocrelizumab either 300mg or 600mg IV infusion. Rate and frequency of NCI CTCAE v4.0 Grade 1-4 IRRs. |
| Percentage of Participants With IRRs Treated With the 300 mg Shorter Dose of Ocrelizumab | During or within 24 hours of administration | This outcome measure evaluate the occurrence of severe IRRs with ocrelizumab 300 mg administered over the course of 1.5 hours. Rate and frequency of NCI CTCAE v4.0 Grade 3-4 IRRs. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 This cohort examined the effect of administering ocrelizumab per a shorter infusion protocol for Dose 2 or Dose 3. Participants who had already received one or two doses of ocrelizumab according to the approved infusion protocol and had reported no serious infusion-related reactions (IRRs) were enrolled. They then received 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 was administered at Week 24, Dose 3 was administered at Week 48 after initial infusion. | 95 |
| Cohort 2 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. | 46 |
| Total | 141 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 8 |
Baseline characteristics
| Characteristic | Total | Cohort 2 | Cohort 1 |
|---|---|---|---|
| Age, Continuous | 41.52 Years STANDARD_DEVIATION 8.75 | 41.07 Years STANDARD_DEVIATION 8.74 | 41.75 Years STANDARD_DEVIATION 8.8 |
| Race/Ethnicity, Customized Black or African American | 16 Participants | 8 Participants | 8 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 7 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 129 Participants | 41 Participants | 88 Participants |
| Race/Ethnicity, Customized Unknown | 5 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 121 Participants | 35 Participants | 86 Participants |
| Sex: Female, Male Female | 93 Participants | 34 Participants | 59 Participants |
| Sex: Female, Male Male | 48 Participants | 12 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 95 | 0 / 46 |
| other Total, other adverse events | 46 / 95 | 7 / 46 |
| serious Total, serious adverse events | 0 / 95 | 0 / 46 |
Outcome results
Primary
Percentage of Participants With Infusion-related Reaction (IRR) Treated With 600 mg IV Ocrelizumab
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
Time frame: During or within 24 hours of administration
Population: The Safety population was the same as the ITT population in this study. All enrolled participants received study treatment, hence treatment group comparability is not applicable. The analysis was conducted in Cohort 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Percentage of Participants With Infusion-related Reaction (IRR) Treated With 600 mg IV Ocrelizumab | 0 Percentage of Participants |
Secondary
Percentage of Participants With IRRs
This outcome measure evaluates the occurrence of overall IRRs with ocrelizumab either 300mg or 600mg IV infusion. Rate and frequency of NCI CTCAE v4.0 Grade 1-4 IRRs.
Time frame: During or within 24 hours of administration
Population: The Safety Population was defined as all enrolled participants who received any dose of study treatment, even if the infusion was incomplete. All enrolled participants received study treatment. The Safety population was the same as the ITT population in this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Percentage of Participants With IRRs | 48.4 Percentage of Participants |
| Cohort 2 | Percentage of Participants With IRRs | 10.9 Percentage of Participants |
Secondary
Percentage of Participants With IRRs Treated With the 300 mg Shorter Dose of Ocrelizumab
This outcome measure evaluate the occurrence of severe IRRs with ocrelizumab 300 mg administered over the course of 1.5 hours. Rate and frequency of NCI CTCAE v4.0 Grade 3-4 IRRs.
Time frame: During or within 24 hours of administration
Population: The Safety population was the same as the ITT population in this study. All enrolled participants received study treatment, hence treatment group comparability is not applicable. The analysis was conducted in Cohort 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Percentage of Participants With IRRs Treated With the 300 mg Shorter Dose of Ocrelizumab | 0 Percentage of Participants |