Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorders
Conditions
Keywords
NMO, NMOSD, Neuromyelitis Optica, Neuromyelitis Optica Spectrum Disorders, autoimmune, demyelination, MEDI-551, monoclonal antibody, Devic's syndrome, B-cell
Brief summary
To compare the efficacy of inebilizumab (MEDI-551) versus placebo in reducing the risk of an neuromyelitis optica/neuromyelitis optica- spectrum disorders (NMO/NMOSD) attack in participants with NMO/NMOSD.
Detailed description
Inebilizumab is a genetically engineered humanized monoclonal antibody that binds to the B cell specific surface antigen cluster of differentiation (CD19) resulting in the depletion of B cells. Inebilizumab depletes antibody-secreting plasmablasts and some plasma cells, which are generally CD19 positive and CD20 negative. The main objective of this study is to determine whether inebilizumab compare to placebo decreases the risk of an attack in participants with NMO/NMOSD. This is a multicenter, multinational, randomized, double-masked, placebo controlled study with an open-label extension period to evaluate the efficacy and safety of intravenous (IV) inebilizumab in adult participants with NMO/NMOSD. After a screening period, eligible participants will enter a randomized-controlled period (RCP) of maximum 197 days where they will be randomized in a 3:1 ratio to receive either IV inebilizumab or placebo. NMO/NMOSD attacks will be evaluated by the investigator and confirmed against the attack criteria by an independent Adjudication Committee (AC). Participants for whom the attack was confirmed by the AC will be given the option to enroll into an open label period (OLP) with inebilizumab treatment. Participants who complete the RCP without experiencing an attack will be given the option to enroll into an OLP with inebilizumab treatment. The OLP will continue for a minimum of 1 year and a maximum of 3 years after the last participant enter the OLP. All participants who discontinue from the RCP or the OLP will continue in a Safety Follow-up for a total of 12 months from last dose to evaluate the long-term safety of the investigational product.
Interventions
DRUGInebilizumab
Participants will receive IV inebilizumab 300 mg.
OTHERPlacebo
Participants will receive IV placebo matched to inebilizumab.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men and women 18 years or older with diagnosis of NMO/NMOSD 2. Confirmation of NMO/NMOSD status: 1. AQP4-IgG sero-positive NMO/NMOSD with at least one attack requiring rescue therapy in the last year or two attacks requiring rescue therapy in the last 2 years 2. AQP4-IgG sero-negative NMO with at least one attack requiring rescue therapy in the last year or two attacks requiring rescue therapy in the last 2 years 3. Able and willing to give written informed consent and comply with the requirements of the study protocol. 4. EDSS \<= 7.5 (8 in special circumstances) 5. Men and women of reproductive potential must agree to use a highly effective method of birth control from screening to 6 months after final dose of the investigational product.
Exclusion criteria
1. Lactating and pregnant females 2. Treatment with any investigational agent within 4 weeks of screening 3. Known history of a severe allergy or reaction to any component of the investigational product formulation or history of anaphylaxis following any biologic therapy. 4. Known active severe bacterial, viral, or other infection or any major episode of infection requiring hospitalization. 5. History of alcohol, drug, or chemical abuse, or a recent history of such abuse \< 1 year prior to randomization 6. Receipt of the following at any time prior to randomization: 1. Alemtuzumab 2. Total lymphoid irradiation 3. Bone marrow transplant 4. T-cell vaccination therapy 7. Receipt of rituximab or any experimental B-cell depleting agent within 6 months prior screening and B-cells below the lower limit of normal. 8. Receipt of intravenous immunoglobulin (IVIG) within 1 month prior to randomization. 9. Receipt of any of the following within 3 months prior to randomization: 1. Natalizumab (Tysabri®). 2. Cyclosporin 3. Methotrexate 4. Mitoxantrone 5. Cyclophosphamide 6. Tocilizumab 7. Eculizumab 10. History of Hepatitis B and/or Hepatitis C (Hep B/C at screening) 11. Known history of a primary immunodeficiency (congenital or acquired) or an underlying condition such as human immunodeficiency virus (HIV) infection 12. History of malignancies, apart from squamous cell or basal cell carcinoma of the skin treated with documented success of curative therapy \> 3 months prior to randomization 13. Any concomitant disease other than NMO/NMOSD that required treatment with oral or intravenous steroids at doses over 20 mg a day for over 21 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Adjudication Committee (AC)-Determined Neuromyelitis Optica Spectrum Disorder (NMOSD) Attack During RCP | Day 1 (Baseline) through Day 197 | The NMOSD attack is defined as the presence of new or worsening symptom(s) related to NMOSD that meet at least one of the 18 protocol-defined attack criteria. These criteria were developed in conjunction with a panel of disease experts and with Food and Drug Administration input, and were intended to be clinically meaningful, objective, quantifiable, and able to be used worldwide. Only attacks positively adjudicated by the AC were used for the primary analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Low-Contrast Visual Acuity Binocular Score to the Last Visit of RCP | Day 1 (Baseline) through Day 197 | Low-contrast visual acuity test is used to determine the number of letters that can be read on a standardized low-contrast Landolt C Broken Rings Chart held at a distance of 3 meters. Binocular score is the number of letters read correctly on an eye chart using both eyes simultaneously. The total score ranges from 0-70. Higher score indicates better vision. |
| Cumulative Number of Active Magnetic Resonance Imaging (MRI) Lesions During RCP | From Screening (Day -28) to Day 197 | The number of new gadolinium-enhancing lesions and new or enlarging T2 lesions were measured by MRI of the brain, optic nerve, and spinal cord. |
| Number of NMOSD-related In-patient Hospitalizations During RCP | Day 1 (Baseline) through Day 197 | Participants with relapsing NMOSD have recurrent attacks that can be severe and result in blindness, paralysis, and even death and consequently, such attacks frequently result in in-patient hospitalizations. In-patient hospitalization is defined as a stay in hospital that goes beyond midnight of the first day of admission. |
| Annualized AC-determined NMOSD Attack Rate During Any Exposure to Inebilizumab | For participants randomized to inebilizumab: Day 1 of RCP through end of OLP (approximately 3.5 years); and for participants randomized to placebo: Day 1 of OLP through the end of OLP (approximately 3 years) | Annualized attack rate is defined as total number of AC-determined attacks divided by total person years. Total person-years is calculated as the sum of the person-years for individual participant. Person-year for individual participant = (Date of last day before safety follow-up period - first inebilizumab dose date +1)/365.25. Annualized AC-determined NMOSD attack rate during any exposure to inebilizumab (in RCP and OLP) is reported. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) During RCP | Day 1 (Baseline) through Day 197 | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug during the RCP. |
| Number of Participants With TEAEs and TESAEs During OLP | Day 198 through end of OLP period (maximum of 3 years after the last participant entered, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years) | An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug during the OLP. |
| Number of Participants With TEAEs and TESAEs During SFP (Open-label Population) | Every 3 months for a total of 1 year after the last dose of study drug (approximately 3 years) | An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug during the OLP. Participant who prematurely discontinued from the RCP or OLP entered in the SFP. |
| Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the Last Visit of RCP | Day 1 (Baseline) through Day 197 | EDSS and its associated functional system (FS) score provide a system for quantifying disability and monitoring changes in the level of disability over time. EDSS is a scale for assessing neurologic impairment in multiple sclerosis (MS). It consists of 7 FS (visual FS, brainstem FS, pyramidal FS, cerebellar FS, sensory FS, bowel and bladder FS, and cerebral FS) which are used to derive EDSS score ranging from 0 (normal neurological exam) to 10 (death from MS). A negative change from baseline indicates improvement. A participant was considered to have a worsening in overall EDSS score of at least 2 if baseline EDSS score was 0, or at least 1 point if baseline EDSS score is 1 to 5, or at least 0.5 point if baseline EDSS score is 5.5 or more. |
| Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Day 1 (Baseline) through Day 197 | Number of participants with at least a 2-grade shift from baseline to worst toxicity grade in hematology and chemistry during RCP is reported. |
| Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Day 198 through end of OLP (maximum of 3 years after the last participant enters, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years) | Number of participants with at least a 2-grade shift from baseline to worst toxicity grade in hematology and chemistry during OLP is reported. |
| Time to Maximum Serum Concentration (Tmax) of Inebilizumab (During RCP) | Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197) | Time to maximum serum concentration of inebilizumab during RCP is reported. |
| Maximum Observed Serum Concentration (Cmax) of Inebilizumab (During RCP) | Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197) | Maximum observed serum concentration of inebilizumab during RCP is reported. |
| Area Under the Serum Concentration Time Curve of the Dosing Interval (AUC0-14d) of Inebilizumab (During RCP) | Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197) | Area under the serum concentration time curve of the dosing interval (AUC0-14d) of inebilizumab during RCP is reported. |
| Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP) | Pre and post dose on Day 1; and on Days 29, 85, and 197 | Number of participants with positive ADA titer to inebilizumab during RCP is reported. |
| Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP) | Pre and post dose on Day 1; and on Days 92, 183, 274, and then every 6 months (maximum of 3 years after the last participant enters, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years) | Number of participants with positive ADA titer to inebilizumab in OLP is reported. |
| Number of Participants With TEAEs and TESAEs During SFP (Non-OLP Population) | Every 3 months for a total of 1 year after the last dose of study drug (approximately 3 years) | An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug during the OLP. The SFP started when a participant prematurely discontinues from the RCP or OLP. |
Countries
Australia, Bulgaria, Canada, Colombia, Czechia, Estonia, Germany, Hong Kong, Hungary, Israel, Japan, Mexico, Moldova, New Zealand, Peru, Poland, Russia, Serbia, South Africa, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Inebilizumab Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug. | 56 |
| Inebilizumab/Inebilizumab AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug. | 174 |
| Total | 230 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Open-label Period (OLP) | Adverse Event | 1 | 2 |
| Open-label Period (OLP) | Death | 1 | 2 |
| Open-label Period (OLP) | Lost to Follow-up | 0 | 1 |
| Open-label Period (OLP) | Other | 6 | 15 |
| Open-label Period (OLP) | Withdrawal by Subject | 0 | 14 |
| Randomized-controlled Period (RCP) | Adverse Event | 0 | 2 |
| Randomized-controlled Period (RCP) | Other | 1 | 2 |
| Randomized-controlled Period (RCP) | Participants randomized, but not treated | 0 | 1 |
| Randomized-controlled Period (RCP) | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Inebilizumab/Inebilizumab | Total | Placebo/Inebilizumab |
|---|---|---|---|
| Age, Continuous | 43.0 Years STANDARD_DEVIATION 11.6 | 42.9 Years STANDARD_DEVIATION 12.2 | 42.6 Years STANDARD_DEVIATION 13.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 28 Participants | 43 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 146 Participants | 187 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 14 Participants | 19 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 39 Participants | 47 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 20 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants | 23 Participants | 10 Participants |
| Race (NIH/OMB) White | 92 Participants | 120 Participants | 28 Participants |
| Sex: Female, Male Female | 159 Participants | 209 Participants | 50 Participants |
| Sex: Female, Male Male | 15 Participants | 21 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 56 | 2 / 174 |
| other Total, other adverse events | 48 / 56 | 138 / 174 |
| serious Total, serious adverse events | 24 / 56 | 28 / 174 |
Outcome results
Primary
Time to Adjudication Committee (AC)-Determined Neuromyelitis Optica Spectrum Disorder (NMOSD) Attack During RCP
The NMOSD attack is defined as the presence of new or worsening symptom(s) related to NMOSD that meet at least one of the 18 protocol-defined attack criteria. These criteria were developed in conjunction with a panel of disease experts and with Food and Drug Administration input, and were intended to be clinically meaningful, objective, quantifiable, and able to be used worldwide. Only attacks positively adjudicated by the AC were used for the primary analysis.
Time frame: Day 1 (Baseline) through Day 197
Population: The ITT population included all participants who were randomized, received any study drug, and grouped according to their randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo/Inebilizumab | Time to Adjudication Committee (AC)-Determined Neuromyelitis Optica Spectrum Disorder (NMOSD) Attack During RCP | NA Days |
| Inebilizumab/Inebilizumab | Time to Adjudication Committee (AC)-Determined Neuromyelitis Optica Spectrum Disorder (NMOSD) Attack During RCP | NA Days |
p-value: <0.000195% CI: [0.1496, 0.4961]Regression, Cox
Secondary
Annualized AC-determined NMOSD Attack Rate During Any Exposure to Inebilizumab
Annualized attack rate is defined as total number of AC-determined attacks divided by total person years. Total person-years is calculated as the sum of the person-years for individual participant. Person-year for individual participant = (Date of last day before safety follow-up period - first inebilizumab dose date +1)/365.25. Annualized AC-determined NMOSD attack rate during any exposure to inebilizumab (in RCP and OLP) is reported.
Time frame: For participants randomized to inebilizumab: Day 1 of RCP through end of OLP (approximately 3.5 years); and for participants randomized to placebo: Day 1 of OLP through the end of OLP (approximately 3 years)
Population: Any inebilizumab population included all participants who received at least one dose of inebilizumab either in the RCP or OLP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Inebilizumab | Annualized AC-determined NMOSD Attack Rate During Any Exposure to Inebilizumab | 0.086 Annualized attack rate |
Secondary
Area Under the Serum Concentration Time Curve of the Dosing Interval (AUC0-14d) of Inebilizumab (During RCP)
Area under the serum concentration time curve of the dosing interval (AUC0-14d) of inebilizumab during RCP is reported.
Time frame: Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197)
Population: The ITT population included all participants who were randomized, received any study drug, and grouped according to their randomized treatment. 'Number analyzed' signifies participants who had adequate pharmacokinetic sample of inebilizumab per the specified dose levels (Dose 1 and Dose 2).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Inebilizumab | Area Under the Serum Concentration Time Curve of the Dosing Interval (AUC0-14d) of Inebilizumab (During RCP) | Dose 1 | 667 μg*d/mL | Geometric Coefficient of Variation 31.3 |
| Placebo/Inebilizumab | Area Under the Serum Concentration Time Curve of the Dosing Interval (AUC0-14d) of Inebilizumab (During RCP) | Dose 2 | 967 μg*d/mL | Geometric Coefficient of Variation 39.6 |
Secondary
Change From Baseline in Low-Contrast Visual Acuity Binocular Score to the Last Visit of RCP
Low-contrast visual acuity test is used to determine the number of letters that can be read on a standardized low-contrast Landolt C Broken Rings Chart held at a distance of 3 meters. Binocular score is the number of letters read correctly on an eye chart using both eyes simultaneously. The total score ranges from 0-70. Higher score indicates better vision.
Time frame: Day 1 (Baseline) through Day 197
Population: The ITT population included all participants who were randomized, received any study drug, and grouped according to their randomized treatment. Participants with low contrast visual acuity binocular score were analyzed for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Inebilizumab | Change From Baseline in Low-Contrast Visual Acuity Binocular Score to the Last Visit of RCP | 1.442 Score on scale | Standard Error 1.217 |
| Inebilizumab/Inebilizumab | Change From Baseline in Low-Contrast Visual Acuity Binocular Score to the Last Visit of RCP | 1.576 Score on scale | Standard Error 0.935 |
p-value: 0.902695% CI: [-2.0254, 2.2941]ANCOVA
Secondary
Cumulative Number of Active Magnetic Resonance Imaging (MRI) Lesions During RCP
The number of new gadolinium-enhancing lesions and new or enlarging T2 lesions were measured by MRI of the brain, optic nerve, and spinal cord.
Time frame: From Screening (Day -28) to Day 197
Population: The ITT population included all participants who were randomized, received any study drug, and grouped according to their randomized treatment. Participants with observed MRI lesions were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Inebilizumab | Cumulative Number of Active Magnetic Resonance Imaging (MRI) Lesions During RCP | 2.3 Number of lesions | Standard Deviation 1.3 |
| Inebilizumab/Inebilizumab | Cumulative Number of Active Magnetic Resonance Imaging (MRI) Lesions During RCP | 1.6 Number of lesions | Standard Deviation 1 |
p-value: 0.003495% CI: [0.3866, 0.8279]Negative Binomial Regression
Secondary
Maximum Observed Serum Concentration (Cmax) of Inebilizumab (During RCP)
Maximum observed serum concentration of inebilizumab during RCP is reported.
Time frame: Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197)
Population: The ITT population included all participants who were randomized, received any study drug, and grouped according to their randomized treatment. 'Number analyzed' signifies participants who had adequate pharmacokinetic sample of inebilizumab per the specified dose levels (Dose 1 and Dose 2).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Inebilizumab | Maximum Observed Serum Concentration (Cmax) of Inebilizumab (During RCP) | Dose 1 | 97.7 μg/mL | Geometric Coefficient of Variation 37.4 |
| Placebo/Inebilizumab | Maximum Observed Serum Concentration (Cmax) of Inebilizumab (During RCP) | Dose 2 | 108 μg/mL | Geometric Coefficient of Variation 45.4 |
Secondary
Number of NMOSD-related In-patient Hospitalizations During RCP
Participants with relapsing NMOSD have recurrent attacks that can be severe and result in blindness, paralysis, and even death and consequently, such attacks frequently result in in-patient hospitalizations. In-patient hospitalization is defined as a stay in hospital that goes beyond midnight of the first day of admission.
Time frame: Day 1 (Baseline) through Day 197
Population: The ITT population included all participants who were randomized, received any study drug, and grouped according to their randomized treatment. Participants with in-patient hospitalization were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Inebilizumab | Number of NMOSD-related In-patient Hospitalizations During RCP | 1.4 Number of In-patient Hospitalizations | Standard Deviation 0.7 |
| Inebilizumab/Inebilizumab | Number of NMOSD-related In-patient Hospitalizations During RCP | 1.0 Number of In-patient Hospitalizations | Standard Deviation 0 |
p-value: 0.014695% CI: [0.1257, 0.7972]Negative Binomial Regression
Secondary
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP
Number of participants with at least a 2-grade shift from baseline to worst toxicity grade in hematology and chemistry during OLP is reported.
Time frame: Day 198 through end of OLP (maximum of 3 years after the last participant enters, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years)
Population: Open-label population included all participants who received at least one dose of study drug during OLP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Hemoglobin (decreased) | 2 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Leukocytes (decreased) | 1 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Lymphocytes (decreased) | 9 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Lymphocytes (increased) | 1 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Neutrophils (decreased) | 1 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Alanine aminotransferase (increased) | 4 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Albumin (decreased) | 0 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Alkaline phosphatase (increased) | 1 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Aspartate aminotransferase (increased) | 2 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Cholesterol (increased) | 1 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Creatinine (increased) | 3 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Gamma glutamyl transferase (increased) | 1 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Glucose (decreased) | 0 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Glucose (increased) | 5 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Potassium (decreased) | 0 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Potassium (increased) | 1 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Sodium (decreased) | 2 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Triglycerides (increased) | 4 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Urate (increased) | 1 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Hemoglobin (increased) | 0 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Bilirubin | 2 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Creatinine (increased) | 7 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Hemoglobin (decreased) | 6 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Urate (increased) | 1 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Leukocytes (decreased) | 12 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Gamma glutamyl transferase (increased) | 10 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Lymphocytes (decreased) | 21 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Sodium (decreased) | 1 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Lymphocytes (increased) | 4 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Glucose (decreased) | 3 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Neutrophils (decreased) | 16 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Bilirubin | 0 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Alanine aminotransferase (increased) | 2 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Glucose (increased) | 5 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Albumin (decreased) | 3 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Triglycerides (increased) | 6 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Alkaline phosphatase (increased) | 1 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Potassium (decreased) | 1 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Aspartate aminotransferase (increased) | 3 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Hemoglobin (increased) | 1 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Cholesterol (increased) | 5 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP | Potassium (increased) | 2 Participants |
Secondary
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP
Number of participants with at least a 2-grade shift from baseline to worst toxicity grade in hematology and chemistry during RCP is reported.
Time frame: Day 1 (Baseline) through Day 197
Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment received. 'Number of Participants analyzed' signifies participants who were analyzed for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Hemoglobin (decreased) | 0 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Leukocytes (decreased) | 1 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Lymphocytes (decreased) | 5 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Lymphocytes (increased) | 4 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Neutrophils (decreased) | 0 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Alanine Aminotransferase (increased) | 1 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Aspartate Aminotransferase (increased) | 2 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Bilirubin (increased) | 2 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Cholesterol (increased) | 2 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Creatinine (increased) | 1 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Gamma glutamyl transferase (increased) | 1 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Glucose (decreased) | 1 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Glucose (increased) | 5 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Potassium (decreased) | 0 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Sodium (decreased) | 1 Participants |
| Placebo/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Triglycerides (increased) | 2 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Triglycerides (increased) | 7 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Hemoglobin (decreased) | 2 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Cholesterol (increased) | 5 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Leukocytes (decreased) | 11 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Glucose (increased) | 1 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Lymphocytes (decreased) | 35 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Creatinine (increased) | 5 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Lymphocytes (increased) | 1 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Sodium (decreased) | 2 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Neutrophils (decreased) | 10 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Gamma glutamyl transferase (increased) | 6 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Alanine Aminotransferase (increased) | 4 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Potassium (decreased) | 1 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Aspartate Aminotransferase (increased) | 1 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Glucose (decreased) | 1 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP | Bilirubin (increased) | 1 Participants |
Secondary
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP)
Number of participants with positive ADA titer to inebilizumab in OLP is reported.
Time frame: Pre and post dose on Day 1; and on Days 92, 183, 274, and then every 6 months (maximum of 3 years after the last participant enters, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years)
Population: Open-label population included all participants who received at least one dose of inebilizumab during OLP. 'Number analyzed' signifies the number of participants who had adequate ADA samples.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo/Inebilizumab | Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP) | ADA positive at any time including baseline (BL) | 9 Participants |
| Placebo/Inebilizumab | Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP) | ADA positive at BL; not detected post-BL | 0 Participants |
| Placebo/Inebilizumab | Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP) | ADA positive post-BL and positive at BL | 4 Participants |
| Placebo/Inebilizumab | Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP) | ADA positive post-BL; not detected at BL | 5 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP) | ADA positive post-BL; not detected at BL | 10 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP) | ADA positive at any time including baseline (BL) | 22 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP) | ADA positive post-BL and positive at BL | 7 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP) | ADA positive at BL; not detected post-BL | 5 Participants |
Secondary
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP)
Number of participants with positive ADA titer to inebilizumab during RCP is reported.
Time frame: Pre and post dose on Day 1; and on Days 29, 85, and 197
Population: The ITT population included all participants who were randomized, received any study drug, and grouped according to their randomized treatment. 'Number analyzed' signifies the number of participants who had adequate ADA samples.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo/Inebilizumab | Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP) | ADA positive at anytime including baseline (BL) | 8 Participants |
| Placebo/Inebilizumab | Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP) | ADA positive at BL; not detected post-BL | 0 Participants |
| Placebo/Inebilizumab | Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP) | ADA positive post-BL; positive at BL | 4 Participants |
| Placebo/Inebilizumab | Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP) | ADA positive post-BL; not detected at BL | 4 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP) | ADA positive post-BL; not detected at BL | 5 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP) | ADA positive at anytime including baseline (BL) | 17 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP) | ADA positive post-BL; positive at BL | 7 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP) | ADA positive at BL; not detected post-BL | 5 Participants |
Secondary
Number of Participants With TEAEs and TESAEs During OLP
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug during the OLP.
Time frame: Day 198 through end of OLP period (maximum of 3 years after the last participant entered, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years)
Population: Open-label population included all participants who received at least one dose of inebilizumab during OLP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo/Inebilizumab | Number of Participants With TEAEs and TESAEs During OLP | TEAEs | 45 Participants |
| Placebo/Inebilizumab | Number of Participants With TEAEs and TESAEs During OLP | TESAEs | 19 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With TEAEs and TESAEs During OLP | TEAEs | 144 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With TEAEs and TESAEs During OLP | TESAEs | 22 Participants |
Secondary
Number of Participants With TEAEs and TESAEs During SFP (Non-OLP Population)
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug during the OLP. The SFP started when a participant prematurely discontinues from the RCP or OLP.
Time frame: Every 3 months for a total of 1 year after the last dose of study drug (approximately 3 years)
Population: Non-OLP population included all participants who received any dose of study drug, analyzed according to the treatment received in RCP, but did not roll over to OLP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo/Inebilizumab | Number of Participants With TEAEs and TESAEs During SFP (Non-OLP Population) | TEAEs | 2 Participants |
| Placebo/Inebilizumab | Number of Participants With TEAEs and TESAEs During SFP (Non-OLP Population) | TESAEs | 1 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With TEAEs and TESAEs During SFP (Non-OLP Population) | TEAEs | 3 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With TEAEs and TESAEs During SFP (Non-OLP Population) | TESAEs | 1 Participants |
Secondary
Number of Participants With TEAEs and TESAEs During SFP (Open-label Population)
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug during the OLP. Participant who prematurely discontinued from the RCP or OLP entered in the SFP.
Time frame: Every 3 months for a total of 1 year after the last dose of study drug (approximately 3 years)
Population: Open-label population included all participants who received at least one dose of inebilizumab during OLP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo/Inebilizumab | Number of Participants With TEAEs and TESAEs During SFP (Open-label Population) | TEAEs | 3 Participants |
| Placebo/Inebilizumab | Number of Participants With TEAEs and TESAEs During SFP (Open-label Population) | TESAEs | 2 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With TEAEs and TESAEs During SFP (Open-label Population) | TEAEs | 5 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With TEAEs and TESAEs During SFP (Open-label Population) | TESAEs | 1 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) During RCP
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug during the RCP.
Time frame: Day 1 (Baseline) through Day 197
Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo/Inebilizumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) During RCP | TEAEs | 41 Participants |
| Placebo/Inebilizumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) During RCP | TESAEs | 6 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) During RCP | TEAEs | 127 Participants |
| Inebilizumab/Inebilizumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) During RCP | TESAEs | 9 Participants |
Secondary
Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the Last Visit of RCP
EDSS and its associated functional system (FS) score provide a system for quantifying disability and monitoring changes in the level of disability over time. EDSS is a scale for assessing neurologic impairment in multiple sclerosis (MS). It consists of 7 FS (visual FS, brainstem FS, pyramidal FS, cerebellar FS, sensory FS, bowel and bladder FS, and cerebral FS) which are used to derive EDSS score ranging from 0 (normal neurological exam) to 10 (death from MS). A negative change from baseline indicates improvement. A participant was considered to have a worsening in overall EDSS score of at least 2 if baseline EDSS score was 0, or at least 1 point if baseline EDSS score is 1 to 5, or at least 0.5 point if baseline EDSS score is 5.5 or more.
Time frame: Day 1 (Baseline) through Day 197
Population: The ITT population included all participants who were randomized, received any study drug, and grouped according to their randomized treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Inebilizumab | Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the Last Visit of RCP | 33.9 Percentage of Participants |
| Inebilizumab/Inebilizumab | Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the Last Visit of RCP | 14.9 Percentage of Participants |
p-value: 0.003395% CI: [0.1755, 0.7059]Regression, Logistic
Secondary
Time to Maximum Serum Concentration (Tmax) of Inebilizumab (During RCP)
Time to maximum serum concentration of inebilizumab during RCP is reported.
Time frame: Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197)
Population: The ITT population included all participants who were randomized, received any study drug, and grouped according to their randomized treatment. 'Number analyzed' signifies participants who had adequate pharmacokinetic sample of inebilizumab per the specified dose levels (Dose 1 and Dose 2).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo/Inebilizumab | Time to Maximum Serum Concentration (Tmax) of Inebilizumab (During RCP) | Dose 1 | 0.07 Days |
| Placebo/Inebilizumab | Time to Maximum Serum Concentration (Tmax) of Inebilizumab (During RCP) | Dose 2 | 0.07 Days |