Neuromyelitis Optica Spectrum Disorder, NMOSD
Conditions
Brief summary
Objective of the trial is to describe the efficacy and safety of satralizumab in patients with aquaporin-4 (AQP4) antibody seropositive NMOSD, either treatment naive or inadequate responders to previous treatment with rituximab (RTX) (or its biosimilar)
Detailed description
Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) are severe demyelinating inflammatory autoimmune neurological disorders. The estimated global pooled prevalence of NMOSD is 1.82 per 100 000 people (Etemadifar et al. 2015). The disorder is characterized by inflammatory lesions in the optic nerve, spinal cord, brainstem, and cerebrum; and clinically by optic neuritis (ON) and/or transverse myelitis causing potentially severe motor and sensory impairment, bladder dysfunction, vision loss, pain, and other debilitating symptoms (Wingerchuk et al. 2015). Recovery is variable, and inflammatory attacks often result in permanent disability. Untreated, the risks of severe disability or death are substantial (Jarius et al. 2014). NMOSD is radiologically and prognostically distinct from multiple sclerosis (MS), and has a pathophysiology unresponsive to typical MS treatment (Weinshenker 2007; Oh, and Levy et al. 2012).
Interventions
DRUGSatralizumab 120 mg
Satralizumab 120 mg will be administered as monotherapy (SC) in the abdominal or femoral region at Weeks 0, 2 (±3 days), 4 (±3 days), and then every 4 weeks (±3 days) till the last administration at Week 92 followed by a clinical evaluation at Week 96. The first dose at Weeks 0 (baseline visit) will be administered at the study site by the designated site staff during the scheduled study visit. The next dose at Week 2 will be self-administered by the patient under the supervision of a designated study staff at the study site. All the subsequent doses will be self-administered by the patient following training from a healthcare provider (for patients who are not able to administer satralizumab SC by themselves, support by a caregiver/nurse is advised).
Sponsors
Chugai Pharmaceutical Co.
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 74 years, inclusive, at the time of informed consent * Have a diagnosis of AQP4 antibody seropositive NMOSD according to the International Panel for NMO Diagnosis (IPND) criteria * For women of childbearing potential: agreement to either remain abstinent (refrain from heterosexual intercourse) or to use reliable means of contraception (physical barrier \[patient or partner\] in conjunction with a spermicidal product, contraceptive pill, patch, injectables, intrauterine device or intrauterine system) during the treatment period and for at least 3 months after the last dose of study drug Cohort 1 (treatment-naïve NMOSD patients) * Confirmation of NMOSD diagnosis with AQP4+ antibodies * Have clinical evidence of at least 1 documented attack or relapse (including first attack) in the last year prior to screening * Naive to maintenance therapy (disease-modifying therapy \[DMT\] or immunosuppressive therapy \[IST\]) Cohort 2 (NMOSD patients with inadequate response to RTX \[or its biosimilar\]) * Confirmation of NMOSD diagnosis and AQP4+ antibodies in the disease history of the patient * Have a length of disease duration from first symptom of ≤5 years * History of ongoing treatment with RTX (or its biosimilar) (at least 2 infusions) for NMOSD with a maximum duration of 6 months since last administration prior to enrolment in the study * Ongoing disease activity after last RTX (or its biosimilar) infusion i.e., relapse and/or any new inflammatory event, confirmed by magnetic resonance imaging (MRI) or ophthalmological assessment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks | Up to 24 weeks | EDSS was a quantitative measure of disability and for assessment of severity of relapse for participants with NMOSD. The overall score ranges from 0 points (normal neurological examination) up to 10 points (death), increasing in increments of 0.5 points. Higher scores represent increased disability. CDP was defined as 1-point or greater worsening in EDSS from baseline that is not attributable to another etiology when the baseline score is 5.5 or less, and ≥ 0.5 when the baseline score is above 5.5. Disability progression was considered confirmed when the increase in the EDSS is confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening. |
| Percentage of Relapse-Free Participants | Up to 14 months | Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse. |
| Annualized Relapse Rate (ARR) | Up to 14 months | The ARR was calculated descriptively by dividing the total number of relapses for all participants by the total years of drug exposure. Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse. |
| Time to First Relapse (TFR) | Up to 14 months | TFR was defined as the time from first dose of satralizumab to the first occurrence of relapse. Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse. |
| Percentage of Participants Hospitalized Due to Relapse | Up to 14 months | Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse. The severity of relapses was assessed based on the occurrence of hospitalization. |
| Percentage of Participants Using Corticosteroids Due to Relapse | Up to 14 months | Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse. The severity of relapses was assessed based on use of corticosteroids. |
| Percentage of Participants in Need of Rescue Therapy Due to Relapse | Up to 14 months | Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse. The severity of relapses was assessed based on the need of rescue therapy. Rescue therapy for clinical relapse included pulse intravenous (IV) corticosteroids, oral corticosteroids for tapering, intravenous immunoglobulin (IVIG) and/or apheresis (including plasma exchange and plasmapheresis). |
| Percentage of Participants in Need of Plasma Exchange Due to Relapse | Up to 14 months | Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse. The severity of relapses was assessed based on the need for plasma exchange. |
| Percentage of Participants With Residual Disability Due to Relapse | Up to 14 months | Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse. |
| Change From Baseline in Expanded Disability Status Scale (EDSS) Score | Up to Week 36 | EDSS was a quantitative measure of disability and for assessment of severity of relapse for participants with NMOSD. The overall score ranges from 0 points (normal neurological examination) up to 10 points (death), increasing in increments of 0.5 points. Higher scores represent increased disability. A negative change from baseline indicates improvement. |
| Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 12 Weeks | Up to 12 weeks | EDSS was a quantitative measure of disability and for assessment of severity of relapse for participants with NMOSD. The overall score ranges from 0 points (normal neurological examination) up to 10 points (death), increasing in increments of 0.5 points. Higher scores represent increased disability. CDP was defined as 1-point or greater worsening in EDSS from baseline that is not attributable to another etiology when the baseline score is 5.5 or less, and ≥ 0.5 when the baseline score is above 5.5. Disability progression was considered confirmed when the increase in the EDSS is confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening. |
| Change From Baseline in the Symbol Digital Modalities Test (SDMT) | Baseline, Week 24 | SDMT testing was to detect impairment of key neurocognitive functions that underlie many substitution tasks, including sustained attention, visual scanning, and recent memory. The test consisted of a sequence of 110 symbols displayed in a maximum 90 seconds and a reference key legend with 9 symbols in a given order and their respective matching digits from 1 to 9. The test measures the speed (number of correct paired responses) to pair abstract symbols with specific digits in 90 seconds time. The score is the number of correctly paired items in 90 seconds with a maximum score of 110 and minimum of 0. Higher scores indicate improvement. |
| Change in High Contrast (100%) and Low Contrast (2.5%) Visual Acuity Using High-and Low-contrast Letter Acuity (LCLA) Charts | Baseline and Week 24 | Best corrected high-contrast (100%) and low-contrast (2.5%) visual acuities were measured at distances of both 4 and 1 meters with the appropriate eye charts. Each eye was tested individually. No visual acuities were obtained with both eyes open. The participants read the charts from left to right starting with the top line (largest letters). The participants proceeded to each lower line until he/she could not see the letters. The total number of letters read correctly were recorded for each eye. Visual acuity was measured before any drops are instilled into the eye and before OCT assessments. |
| Change in Visual Functioning Questionnaire -25 (VFQ-25) | At Week 24 | The National Eye institute (NEI) VFQ-25 captures a participants's perception of vision-related functioning and vision-related quality of life. The core measures include 25 items that comprise 11 vision-related subscales and one item on general health. The NEI VFQ-25 also included an appendix of additional items that was used to expand the scales up to 39 total items. The composite score and the subscale scores range from 0 to 100, with higher scores indicating better vision-related functioning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans | Weeks 4, 8, 12 and 24 | MRI was used to monitor central nervous system (CNS) lesions and potentially other pathophysiology, such as inflammation and neurodegeneration. LETM=longitudinally extensive transverse myelitis. Stm=subcortical temporal medial. Count of T2-weighted FLAIR hyperintense lesions (including new and enlarging) were distributed across the following regions: cerebrum, optic nerves, optic chiasm, area postrema, brainstem and cerebellum. |
| Volume of T2-weighted FLAIR Hyperintense Lesions Assessed Using MRI Scans | Baseline, Week 12 | MRI was used to monitor CNS lesions and potentially other pathophysiology, such as inflammation and neurodegeneration. |
| Number of Participants With Contrast-enhancing T1-weighted Lesions (CEL) Assessed Using MRI Scans | Basline, Weeks 4, and 12 | MRI was used to monitor CNS lesions and potentially other pathophysiology, such as inflammation and neurodegeneration. |
| Number of Participants With Diffusion Abnormalities, Microbleeds and Cerebral Perfusion Alterations Assessed Using MRI Scans | Up to 14 Months | — |
| Number of Participants With Global and Regional Brain Volume Loss Assessed Using MRI Scans | Up to 14 Months | — |
| Number of Participants With New and Persisting Short T1 Inversion Recovery (STIR)/ Proton Density (PD) Hyperintense Lesions and T1-weighted Contrast Enhancement Assessed Using MRI Scans | Up to 14 months | — |
| Quantitative T1 Mapping (Magnetization Prepared Rapid Gradient Echo Sequence [MP2RAGE]) Assessed Using MRI Scans | Up to 14 months | — |
| T2*/R* Ratio for Iron Concentration Estimation Assessed Using MRI Scans | Up to 14 months | — |
| Quantitative Diffusion/ Diffusion Tensor Imaging (DTI) Assessed Using MRI Scans | Up to 14 months | — |
| Change in the Retinal Nerve Fiber Layer (RNFL) Thickness Assessed Using Optical Coherence Tomography (OCT) | Up to 14 months | — |
| Change in the Ganglion Cell Plus Inner Plexiform (GCIP) Layer Thickness Assessed Using OCT | Up to 14 months | — |
| Concentration of Satralizumab in Cerebrospinal Fluid (CSF) and Serum | Baseline and Week 12 | — |
| Number of Participants With Anti-satralizumab Antibodies | Up to 14 months | — |
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | Up to 14 months | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above. An AESI included drug induced liver injury and suspected transmission of infectious agent via medicinal products. |
Countries
South Korea, Turkey (Türkiye), United States
Participant flow
Recruitment details
Participants took part in this study at 3 investigative sites in 3 countries.
Pre-assignment details
A total of 4 participants with neuromyelitis optica spectrum disorder (NMOSD) were enrolled in 'Cohort 2: Inadequate Responders to Previous Rituximab (RTX) Treatment' to receive satralizumab. No participants were enrolled in 'Cohort 1: Treatment-naïve Participants' due to early study termination.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment Participants with inadequate response to previous RTX treatment received 120 mg of satralizumab monotherapy as SC injection on Day 1 of Weeks 0, 2, 4 and then Q4W up to Week 92. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study Terminated by Sponsor | 4 |
Baseline characteristics
| Characteristic | Cohort 2: Inadequate Responders to Previous RTX Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 2 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Annualized Relapse Rate (ARR)
The ARR was calculated descriptively by dividing the total number of relapses for all participants by the total years of drug exposure. Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse.
Time frame: Up to 14 months
Population: ITT population included all enrolled participants who received any dose of satralizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Annualized Relapse Rate (ARR) | 0 relapses per participant-year |
Primary
Change From Baseline in Expanded Disability Status Scale (EDSS) Score
EDSS was a quantitative measure of disability and for assessment of severity of relapse for participants with NMOSD. The overall score ranges from 0 points (normal neurological examination) up to 10 points (death), increasing in increments of 0.5 points. Higher scores represent increased disability. A negative change from baseline indicates improvement.
Time frame: Up to Week 36
Population: ITT population included all enrolled participants who received any dose of satralizumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Change From Baseline in Expanded Disability Status Scale (EDSS) Score | 0 score on a scale | Standard Deviation 0 |
Primary
Change From Baseline in the Symbol Digital Modalities Test (SDMT)
SDMT testing was to detect impairment of key neurocognitive functions that underlie many substitution tasks, including sustained attention, visual scanning, and recent memory. The test consisted of a sequence of 110 symbols displayed in a maximum 90 seconds and a reference key legend with 9 symbols in a given order and their respective matching digits from 1 to 9. The test measures the speed (number of correct paired responses) to pair abstract symbols with specific digits in 90 seconds time. The score is the number of correctly paired items in 90 seconds with a maximum score of 110 and minimum of 0. Higher scores indicate improvement.
Time frame: Baseline, Week 24
Population: ITT population included all enrolled participants who received any dose of satralizumab. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Change From Baseline in the Symbol Digital Modalities Test (SDMT) | -5 score on a scale |
Primary
Change in High Contrast (100%) and Low Contrast (2.5%) Visual Acuity Using High-and Low-contrast Letter Acuity (LCLA) Charts
Best corrected high-contrast (100%) and low-contrast (2.5%) visual acuities were measured at distances of both 4 and 1 meters with the appropriate eye charts. Each eye was tested individually. No visual acuities were obtained with both eyes open. The participants read the charts from left to right starting with the top line (largest letters). The participants proceeded to each lower line until he/she could not see the letters. The total number of letters read correctly were recorded for each eye. Visual acuity was measured before any drops are instilled into the eye and before OCT assessments.
Time frame: Baseline and Week 24
Population: ITT population included all enrolled participants who received any dose of satralizumab. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Change in High Contrast (100%) and Low Contrast (2.5%) Visual Acuity Using High-and Low-contrast Letter Acuity (LCLA) Charts | Right High Contrast | -14 Letters correct |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Change in High Contrast (100%) and Low Contrast (2.5%) Visual Acuity Using High-and Low-contrast Letter Acuity (LCLA) Charts | Left High Contrast | 80 Letters correct |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Change in High Contrast (100%) and Low Contrast (2.5%) Visual Acuity Using High-and Low-contrast Letter Acuity (LCLA) Charts | Right Low Contrast | 60 Letters correct |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Change in High Contrast (100%) and Low Contrast (2.5%) Visual Acuity Using High-and Low-contrast Letter Acuity (LCLA) Charts | Left Low Contrast | 33 Letters correct |
Primary
Change in Visual Functioning Questionnaire -25 (VFQ-25)
The National Eye institute (NEI) VFQ-25 captures a participants's perception of vision-related functioning and vision-related quality of life. The core measures include 25 items that comprise 11 vision-related subscales and one item on general health. The NEI VFQ-25 also included an appendix of additional items that was used to expand the scales up to 39 total items. The composite score and the subscale scores range from 0 to 100, with higher scores indicating better vision-related functioning.
Time frame: At Week 24
Population: ITT population included all enrolled participants who received any dose of satralizumab. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Change in Visual Functioning Questionnaire -25 (VFQ-25) | 10 score on a scale |
Primary
Percentage of Participants Hospitalized Due to Relapse
Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse. The severity of relapses was assessed based on the occurrence of hospitalization.
Time frame: Up to 14 months
Population: ITT population included all enrolled participants who received any dose of satralizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Percentage of Participants Hospitalized Due to Relapse | 0 percentage of participants |
Primary
Percentage of Participants in Need of Plasma Exchange Due to Relapse
Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse. The severity of relapses was assessed based on the need for plasma exchange.
Time frame: Up to 14 months
Population: ITT population included all enrolled participants who received any dose of satralizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Percentage of Participants in Need of Plasma Exchange Due to Relapse | 0 percentage of participants |
Primary
Percentage of Participants in Need of Rescue Therapy Due to Relapse
Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse. The severity of relapses was assessed based on the need of rescue therapy. Rescue therapy for clinical relapse included pulse intravenous (IV) corticosteroids, oral corticosteroids for tapering, intravenous immunoglobulin (IVIG) and/or apheresis (including plasma exchange and plasmapheresis).
Time frame: Up to 14 months
Population: ITT population included all enrolled participants who received any dose of satralizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Percentage of Participants in Need of Rescue Therapy Due to Relapse | 0 percentage of participants |
Primary
Percentage of Participants Using Corticosteroids Due to Relapse
Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse. The severity of relapses was assessed based on use of corticosteroids.
Time frame: Up to 14 months
Population: ITT population included all enrolled participants who received any dose of satralizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Percentage of Participants Using Corticosteroids Due to Relapse | 0 percentage of participants |
Primary
Percentage of Participants With Residual Disability Due to Relapse
Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse.
Time frame: Up to 14 months
Population: ITT population included all enrolled participants who received any dose of satralizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Percentage of Participants With Residual Disability Due to Relapse | 0 percentage of participants |
Primary
Percentage of Relapse-Free Participants
Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse.
Time frame: Up to 14 months
Population: ITT population included all enrolled participants who received any dose of satralizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Percentage of Relapse-Free Participants | 100 percentage of participants |
Primary
Time to First Relapse (TFR)
TFR was defined as the time from first dose of satralizumab to the first occurrence of relapse. Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse.
Time frame: Up to 14 months
Population: ITT population included all enrolled participants who received any dose of satralizumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Time to First Relapse (TFR) | NA weeks |
Primary
Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 12 Weeks
EDSS was a quantitative measure of disability and for assessment of severity of relapse for participants with NMOSD. The overall score ranges from 0 points (normal neurological examination) up to 10 points (death), increasing in increments of 0.5 points. Higher scores represent increased disability. CDP was defined as 1-point or greater worsening in EDSS from baseline that is not attributable to another etiology when the baseline score is 5.5 or less, and ≥ 0.5 when the baseline score is above 5.5. Disability progression was considered confirmed when the increase in the EDSS is confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening.
Time frame: Up to 12 weeks
Population: ITT population included all enrolled participants who received any dose of satralizumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 12 Weeks | NA weeks |
Primary
Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks
EDSS was a quantitative measure of disability and for assessment of severity of relapse for participants with NMOSD. The overall score ranges from 0 points (normal neurological examination) up to 10 points (death), increasing in increments of 0.5 points. Higher scores represent increased disability. CDP was defined as 1-point or greater worsening in EDSS from baseline that is not attributable to another etiology when the baseline score is 5.5 or less, and ≥ 0.5 when the baseline score is above 5.5. Disability progression was considered confirmed when the increase in the EDSS is confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening.
Time frame: Up to 24 weeks
Population: ITT population included all enrolled participants who received any dose of satralizumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks | NA weeks |
Secondary
Change in the Ganglion Cell Plus Inner Plexiform (GCIP) Layer Thickness Assessed Using OCT
Time frame: Up to 14 months
Population: Data for this outcome measure was not collected and analyzed as planned as the study was terminated per sponsor's decision.
Secondary
Change in the Retinal Nerve Fiber Layer (RNFL) Thickness Assessed Using Optical Coherence Tomography (OCT)
Time frame: Up to 14 months
Population: Data for this outcome measure was not collected and analyzed as planned as the study was terminated per sponsor's decision.
Secondary
Concentration of Satralizumab in Cerebrospinal Fluid (CSF) and Serum
Time frame: Baseline and Week 12
Population: ITT population included all enrolled participants who received any dose of satralizumab. Data for this CSF concentartion was not collected and analyzed as planned as the study was terminated per sponsor's decision.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Concentration of Satralizumab in Cerebrospinal Fluid (CSF) and Serum | 19078.02 nanograms/litre (ng/L) | Geometric Coefficient of Variation 15.94 |
Secondary
Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans
MRI was used to monitor central nervous system (CNS) lesions and potentially other pathophysiology, such as inflammation and neurodegeneration. LETM=longitudinally extensive transverse myelitis. Stm=subcortical temporal medial. Count of T2-weighted FLAIR hyperintense lesions (including new and enlarging) were distributed across the following regions: cerebrum, optic nerves, optic chiasm, area postrema, brainstem and cerebellum.
Time frame: Weeks 4, 8, 12 and 24
Population: ITT population included all enrolled participants who received any dose of satralizumab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans | Baseline: Hyperintense Lesion | 3 number of lesions |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans | Week 4: Hyperintense Lesion | 3 number of lesions |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans | Week 8: Hyperintense Lesion | 2 number of lesions |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans | Week 12: Hyperintense Lesion | 3 number of lesions |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans | Baseline: Hyperintense Letm Lesion | 2 number of lesions |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans | Week 4: Hyperintense Letm Lesion | 2 number of lesions |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans | Week 8: Hyperintense Letm Lesion | 1 number of lesions |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans | Week 12: Hyperintense Letm Lesion | 1 number of lesions |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans | Baseline: Hyperintense Stm Lesion | 9 number of lesions |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans | Week 4: Hyperintense Stm Lesion | 8 number of lesions |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans | Week 8: Hyperintense Stm Lesion | 8 number of lesions |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans | Week 12: Hyperintense Stm Lesion | 8 number of lesions |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans | Week 24: Hyperintense Lesion | 1 number of lesions |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans | Week 24: Hyperintense Letm Lesion | 0 number of lesions |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans | Week 24: Hyperintense Stm Lesion | 1 number of lesions |
Secondary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above. An AESI included drug induced liver injury and suspected transmission of infectious agent via medicinal products.
Time frame: Up to 14 months
Population: Safety population included all enrolled participants who received any dose of satralizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | AE | 2 Participants |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | SAE | 0 Participants |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | AESIs | 0 Participants |
Secondary
Number of Participants With Anti-satralizumab Antibodies
Time frame: Up to 14 months
Population: Data for this outcome measure was not collected and analyzed as planned as the study was terminated per sponsor's decision.
Secondary
Number of Participants With Contrast-enhancing T1-weighted Lesions (CEL) Assessed Using MRI Scans
MRI was used to monitor CNS lesions and potentially other pathophysiology, such as inflammation and neurodegeneration.
Time frame: Basline, Weeks 4, and 12
Population: ITT population included all enrolled participants who received any dose of satralizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Number of Participants With Contrast-enhancing T1-weighted Lesions (CEL) Assessed Using MRI Scans | 0 Participants |
Secondary
Number of Participants With Diffusion Abnormalities, Microbleeds and Cerebral Perfusion Alterations Assessed Using MRI Scans
Time frame: Up to 14 Months
Population: Data for this outcome measure was not collected and analyzed as planned as the study was terminated per sponsor's decision.
Secondary
Number of Participants With Global and Regional Brain Volume Loss Assessed Using MRI Scans
Time frame: Up to 14 Months
Population: Data for this outcome measure was not collected and analyzed as planned as the study was terminated per sponsor's decision.
Secondary
Number of Participants With New and Persisting Short T1 Inversion Recovery (STIR)/ Proton Density (PD) Hyperintense Lesions and T1-weighted Contrast Enhancement Assessed Using MRI Scans
Time frame: Up to 14 months
Population: Data for this outcome measure was not collected and analyzed as planned as the study was terminated per sponsor's decision.
Secondary
Quantitative Diffusion/ Diffusion Tensor Imaging (DTI) Assessed Using MRI Scans
Time frame: Up to 14 months
Population: Data for this outcome measure was not collected and analyzed as planned as the study was terminated per sponsor's decision.
Secondary
Quantitative T1 Mapping (Magnetization Prepared Rapid Gradient Echo Sequence [MP2RAGE]) Assessed Using MRI Scans
Time frame: Up to 14 months
Population: Data for this outcome measure was not collected and analyzed as planned as the study was terminated per sponsor's decision.
Secondary
T2*/R* Ratio for Iron Concentration Estimation Assessed Using MRI Scans
Time frame: Up to 14 months
Population: Data for this outcome measure was not collected and analyzed as planned as the study was terminated per sponsor's decision.
Secondary
Volume of T2-weighted FLAIR Hyperintense Lesions Assessed Using MRI Scans
MRI was used to monitor CNS lesions and potentially other pathophysiology, such as inflammation and neurodegeneration.
Time frame: Baseline, Week 12
Population: ITT population included all enrolled participants who received any dose of satralizumab. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Volume of T2-weighted FLAIR Hyperintense Lesions Assessed Using MRI Scans | Baseline | 0.2285 milliliter (mL) |
| Cohort 2: Inadequate Responders to Previous RTX Treatment | Volume of T2-weighted FLAIR Hyperintense Lesions Assessed Using MRI Scans | Week 12 | 0.2520 milliliter (mL) |