Primary Outcomes

Description: The primary endpoint of the study will be the change in regional microglial activity in the brain using standardized uptake value ratio (SUVR) measurements at early and late time-points (5, 28, 90 and 273 days) as compared to baseline.

Measure: Effect of Ofatumumab on microglial activity

Time: Baseline to 9 months

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Secondary Outcomes

Description: Association of change in regional microglial activity in the brain using standardized uptake value ratio (SUVR) measurements with changes in the peripheral CD19 counts at 5, 28, 90 and 273 days as compared to baseline. We will calculate the change from day 0 to each of the other time points for each of the measures, and we will estimate the correlation between the changes using Pearson's correlation coefficient.

Measure: Relationship between changes in Microglial activity and CD19 counts

Time: Baseline to 9 months

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Description: Association of change in regional microglial activity in the brain using standardized uptake value ratio (SUVR) measurements with changes in the serum glial fibrillary acid protein (GFAP) level measurements at 5, 28, 90 and 273 days as compared to baseline. We will calculate the change from day 0 to each of the other time points for each of the measures, and we will estimate the correlation between the changes using Pearson's correlation coefficient.

Measure: Relationship between changes in Microglial activity and glial fibrillary acid protein (GFAP)

Time: Baseline to 9 months

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Description: Association of change in regional microglial activity in the brain using standardized uptake value ratio (SUVR) measurements with changes in the serum neurofilament light chain levels at 5, 28, 90 and 273 days as compared to baseline. We will calculate the change from day 0 to each of the other time points for each of the measures, and we will estimate the correlation between the changes using Pearson's correlation coefficient.

Measure: Relationship between changes in Microglial activity and neurofilament light chain

Time: Baseline to 9 months

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Description: Association of change in regional microglial activity in the brain using standardized uptake value ratio (SUVR) measurements with changes in MRI -based brain volume (in ml) measurements at 5, 28, 90 and 273 days as compared to baseline. We will calculate the change from day 0 to each of the other time points for each of the measures, and we will estimate the correlation between the changes using Pearson's correlation coefficient.

Measure: Relationship between changes in Microglial activity and MRI-based brain atrophy changes

Time: Baseline to 9 months

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Description: Association of changes in regional microglial activity in the brain using standardized uptake value ratio (SUVR) measurements with changes in disease severity (measured using expanded disability status scale or EDSS) at 5, 28, 90 and 273 days as compared to baseline. We will calculate the change from day 0 to each of the other time points for each of the measures, and we will estimate the correlation between the changes using Pearson's correlation coefficient.

Measure: Relationship between changes in Microglial activity and physical disability

Time: Baseline to 9 months

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Description: Association of changes in regional microglial activity in the brain using standardized uptake value ratio (SUVR) measurements with changes in severity of cognitive impairment (measured using symbol digit modality test or SDMT) at 5, 28, 90 and 273 days as compared to baseline. We will calculate the change from day 0 to each of the other time points for each of the measures, and we will estimate the correlation between the changes using Pearson's correlation coefficient.

Measure: Relationship between changes in Microglial activity and cognitive disability

Time: Baseline to 9 months

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Primary Outcomes

Description: quantitative ambulation performance test

Measure: Timed 25-Foot Walk (T25W)

Time: up to 12 months

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Secondary Outcomes

Description: brief, standardized, quantitative test of upper extremity

Measure: 9-Hole Peg Test

Time: administered at baseline, one month, 6 months, and 12 months

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Description: measures cognitive processing speed and working memory

Measure: Symbol Digit Modalities Test

Time: administered at baseline, one month, 6 months, and 12 months

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Description: EDSS is the standard measure of neurologic impairment that is used to describe disability in MS. The neurological assessment comprises seven functional systems.

Measure: Functional Systems and Expanded Disability Status Scale (EDSS)

Time: administered at baseline, one month, 6 months, and 12 months

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Description: structured, self-report questionnaire with 21 itmes concerning how fatigue impacts patient's life

Measure: Modified Fatigue Impact Scale (MFIS)

Time: administered at baseline, one month, 6 months, and 12 months

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Description: 54-item multidimensional health-related quality of life measure that combines both generic and MS-specific items

Measure: Multiple Sclerosis Quality of Life Scale 54 item version

Time: administered at baseline, one month, 6 months, and 12 months

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Primary Outcomes

Description: Physiological fall risk will be determined by the physiological profile assessment which assesses physiological function related to fall risk by combining measures of vision, proprioception, lower-limb strength, postural sway, and cognitive function.

Measure: Physiological Fall risk

Time: 3 months

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Secondary Outcomes

Description: Mobility will be quantified with performance on timed 25 foot walk (T25W), timed up and go (TUG), Six spot step test, 6 minute walk and the MS walking scale-12.

Measure: Mobility

Time: 3 months

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Description: Balance will be quantified with the Berg Balance scale; self-report of balance impairment (ABC); and force platform metrics (sway range and velocity).

Measure: Balance

Time: 3 Months

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Description: Spasticity will be assessed with the modified ashworth scale.

Measure: Spasticity

Time: 3 Months

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Primary Outcomes

Measure: Fall incidence

Time: 3 months

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Secondary Outcomes

Description: Physiological fall risk will be determined by the short form of the Physiological Profile Assessment (PPA)(Lord, 2003). The PPA is a standardized test battery which assesses vision (edge contrast sensitivity), lower limb proprioception, strength (knee extension), postural sway, and cognitive function (simple hand reaction time). The outcome of each test will be combined to generate an overall fall risk score

Measure: Physiological Fall Risk

Time: 3 Months

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Description: Specific measures of walking speed, endurance, coordination and self-reported walking function scale will be employed to assess overall mobility of each person. Walking speed was quantified with the Timed 25-Foot Walk (T25W), walking endurance was assessed with the 6-Minute Walk (6MW), and functional mobility was quantified with the Timed Up and Go (TUG) . The Multiple Sclerosis Walking Scale-12 (MSWS-12) will be used as a self-reported measure of walking impairment.

Measure: Mobility

Time: 3 months

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Description: To assess balance (e.g. postural control), we conducted a clinical assessment To measure balance the Berg Balance Scale (BBS) and self-reports of balance confidence will be used. The BBS is a clinical assessment of balance. Scores on the BBS range from 0-56 with higher scores indicating greater balance. The Activities-Specific Balance Confidence (ABC) scale was used as a measure of balance confidence.

Measure: Balance

Time: 3 Months

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Primary Outcomes

Description: PET outcome measure change at 18 months from baseline

Measure: PET Uptake/Standardized uptake value ratio (SUVR) change

Time: baseline and 18 months

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Secondary Outcomes

Description: PET outcome measure change at 6 months from baseline

Measure: PET Uptake/Standardized uptake value ratio (SUVR) change

Time: baseline and 6 months

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Description: MRI outcome measure change at 18 months from baseline

Measure: T2/FLAIR lesion load change

Time: baseline and 18 months

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Description: MRI outcome measure change at 18 months from baseline

Measure: Whole brain/deep gray matter atrophy change

Time: baseline and 18 months

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Description: Clinical outcome measure change at 18 months from baseline; Scale Range: 0-10; Higher values represent worse outcomes

Measure: Expanded Disability Status Scale (EDSS) change

Time: baseline and 18 months

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Description: Clinical outcome measure change at 18 months from baseline

Measure: Timed 25-foot walk (T25FW) change

Time: baseline and 18 months

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Description: Clinical outcome measure change at 18 months from baseline; Physical subscale range: 0-36; Cognitive subscale range: 0-40; Psychosocial subscale range: 0-8; Total MFIS Score scale range (Subscales Summed): 0-84; Higher values represent worse outcomes

Measure: Modified Fatigue Impact Scale (MIFS) change

Time: baseline and 18 months

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Description: Clinical outcome measure change at 18 months from baseline

Measure: Minimal Assessment of Cognitive Function in MS (MACFIMS) change

Time: baseline and 18 months

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Primary Outcomes

Description: TFR was defined as time from randomization to first occurrence of relapse in the DB period. Protocol-defined relapse was occurrence of new or worsening neurological symptoms attributable to neurological neuromyelitis optica (NMO) or neuromyelitis optica spectrum disorder (NMOSD). Symptoms had to persist for >24 hours and not be attributable to confounding clinical factors (e.g., fever, infection, injury, change in mood, adverse reactions to medications). New or worsening neurological symptoms that occurred < 31 days following onset of a protocol-defined relapse were considered part of same relapse (i.e., if 2 relapses had onset days that were 30 days of one another, they were counted only as 1 relapse), and onset date used in analysis was the date of first relapse.

Measure: Time to First Protocol-Defined Relapse (TFR) During the Double-Blind (DB) Period

Time: Up to Week 216

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Secondary Outcomes

Description: The VAS is a subjective measure of pain consisting of a 100 mm line with two endpoints representing 0 = "no pain" and 100 = "pain as bad as it could be". Participants rated their pain by placing a mark on the line corresponding to their current level of pain. The distance along the line from the "no pain" marker was measured with a ruler giving a pain score out of 100. A higher score indicated more pain and lower scores reflected a better health state. A negative change from baseline indicates an improvement. ANCOVA was used for analysis to report the adjusted mean and standard error (SE).

Measure: Change From Baseline to Week 24 in Visual Analogue Scale (VAS) for Pain

Time: Baseline, Week 24

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Description: The FACIT Fatigue scale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the past 7 days. As each of the 13 items of the scale ranges from 0-4, the range of possible scores was computed using FACIT scoring algorithm as 0-52, where 0 is the worst possible score and 52 the best which indicated less fatigue. A positive change from baseline indicates an improvement.

Measure: Change From Baseline to Week 24 in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale

Time: Baseline, Week 24

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Description: Protocol-defined relapse was occurrence of new or worsening neurological symptoms attributable to neurological neuromyelitis optica (NMO) or neuromyelitis optica spectrum disorder (NMOSD). Symptoms had to persist for >24 hours and not be attributable to confounding clinical factors (e.g., fever, infection, injury, change in mood, adverse reactions to medications). New or worsening neurological symptoms that occurred < 31 days following onset of a protocol-defined relapse were considered part of same relapse (i.e., if 2 relapses had onsets within 30 days of one another, they were counted as 1), and onset date used in analysis was the date of first relapse.

Measure: Relapse-Free Rate During the DB Period

Time: Up to Week 216

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Description: The ARR is calculated as the total number of participants with adjudicated PDRs experienced divided by the patient-years at risk. Protocol-defined relapse was occurrence of new or worsening neurological symptoms attributable to neurological NMO or NMOSD. Symptoms had to persist for >24 hours and not be attributable to confounding clinical factors (e.g., fever, infection, injury, change in mood, adverse reactions to medications). New or worsening neurological symptoms that occurred < 31 days following onset of a protocol-defined relapse were considered part of same relapse (2 relapses with onset days in 30 days of one another was counted as 1 relapse), onset date used in analysis was the date of first relapse.

Measure: Annualized Relapse Rate (ARR) During the DB Period

Time: Up to Week 216

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Description: The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement.

Measure: Change From Baseline in Short Form Generic Health Survey (SF-36) Bodily Pain Domain Scores at 24 Week Intervals During the DB Period

Time: Baseline up to Week 216

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Description: The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement.

Measure: Change From Baseline in SF-36 General Health Domain Scores at 24 Week Intervals During the DB Period

Time: Baseline up to Week 216

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Description: The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement.

Measure: Change From Baseline in SF-36 Mental Health Domain Scores at 24 Week Intervals During the DB Period

Time: Baseline up to Week 216

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Description: The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement.

Measure: Change From Baseline in SF-36 Physical Functioning Domain Scores at 24 Week Intervals During the DB Period

Time: Baseline up to Week 216

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Description: The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement.

Measure: Change From Baseline in SF-36 Role-Emotional Domain Scores at 24 Week Intervals During the DB Period

Time: Baseline up to Week 216

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Description: The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement.

Measure: Change From Baseline in SF-36 Role-Physical Domain Scores at 24 Week Intervals During the DB Period

Time: Baseline up to Week 216

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Description: The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement.

Measure: Change From Baseline in SF-36 Social Role Functioning Domain Scores at 24 Week Intervals During the DB Period

Time: Baseline up to Week 216

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Description: The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement.

Measure: Change From Baseline in SF-36 Vitality Domain Scores at 24 Week Intervals During the DB Period

Time: Baseline up to Week 216

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Description: The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health summary measures and a preference-based health utility index. The component scores were transformed to a 0-100 scale, where higher score indicates better quality of life. A positive change from baseline indicates an improvement.

Measure: Change From Baseline in SF-36 Mental Component Summary Scores at 24 Week Intervals During the DB Period

Time: Baseline up to Week 216

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Description: The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health summary measures and a preference-based health utility index. The component scores were transformed to a 0-100 scale, where higher score indicates better quality of life. A positive change from baseline indicates an improvement.

Measure: Change From Baseline in SF-36 Physical Component Summary Scores at 24 Week Intervals During the DB Period

Time: Baseline up to Week 216

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Description: The EQ-5D is a participant-answered questionnaire measuring 5 dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression with 3 possible response categories: 1) no problems; 2) some problems; 3) severe problems. The scores from 5 dimensions are used as input to generate EQ-5D index score using scoring algorithm. The EQ-5D index score is scored on a scale of -0.2 to 1. A higher score reflects a better health state. A positive change from baseline indicates an improvement

Measure: Change From Baseline in EuroQoL-5 Dimensions (EQ-5D) Index Scores at 24 Week Intervals During the DB Period

Time: Baseline up to Week 216

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Description: The T25W is an assessment of walking ability. The time (in seconds) that the participant took to walk 25 feet was measured. Speed is calculated as 1/Timed 25-Foot Walk where time is measured in seconds. A positive change from baseline indicates an improvement.

Measure: Change From Baseline in Speed of Timed 25-Foot Walk (T25W) at 24 Week Intervals During the DB Period

Time: Baseline up to Week 216

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Description: The mRS is a 7-point disability scale that assesses the degree of disability in participants with neurological impairment. Possible scores range from 0 (no symptoms at all) up to 6 (death). Higher scores reflect increased disability. A negative change from baseline indicates an improvement.

Measure: Change From Baseline in Modified Rankin Scale (mRS) Scores at 24 Week Intervals During the DB Period

Time: Baseline up to Week 216

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Description: The ZBI is the measurement to assess caregiver burden. The 22 items ask for the strain caregivers perceive. Responses range from 0 (never) to 4 (nearly always). The overall ZBI score ranges from 0 to 88. The higher the total score, the heavier the perceived burden. A negative change from baseline indicates an improvement.

Measure: Change From Baseline in Zarit Burden Interview (ZBI) Scores at 24 Week Intervals During the DB Period

Time: Baseline up to Week 120

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Description: The EDSS is an ordinal scale with values from 0 points (normal neurological examination) to 10 points (death) increasing in half-point increments once an EDSS of 1.0 has been reached. Higher scores represent increased disability. A negative change from baseline indicates an improvement.

Measure: Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at 24 Week Intervals During the DB Period

Time: Baseline up to Week 216

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Description: Visual acuity was measured using Snellen 20-foot wall chart and then converted to logMAR visual acuity scoring. Lower values indicate better visual acuity. Data are reported for right eye (OD) and left eye (OS). A negative change from baseline indicates an improvement.

Measure: Change From Baseline in Visual Acuity (Snellen Chart) at 24 Week Intervals During the DB Period

Time: Baseline up to Week 216

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Description: The LCSLC evaluates the visual function and captures the minimum size at which individuals can perceive letters of a particular contrast level. The change in binocular visual acuity, as assessed by the number of letters read correctly from a distance of 2 meters on 100%, 2.5% and 1.25% contrast level Sloan letter charts, was analyzed. The LCSLC is scored on a scale of 0-60. Higher scores indicate better visual function. A positive change from baseline indicates an improvement.

Measure: Change From Baseline in Visual Function (Low-Contrast Sloan Letter Chart [LCSLC]) Scores at 24 Week Intervals During the DB Period

Time: Baseline up to Week 216

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Description: An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event 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. Pre-existing conditions which worsen during a study are also considered as adverse events.

Measure: Number of Participants With at Least One Adverse Event in the DB Period

Time: Up to Week 216

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Description: A serious adverse event is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is medically significant or requires intervention to prevent one or other of the outcomes listed above.

Measure: Number of Participants With at Least One Serious Adverse Event in the DB Period

Time: Up to Week 216

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Description: Non-serious adverse events of special interest for this study included: 1) cases of an elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) in combination with either an elevated bilirubin or clinical jaundice, 2) suspected transmission of an infectious agent by the study treatment.

Measure: Number of Participants With Non-Serious Adverse Events of Special Interest in the DB Period

Time: Up to Week 216

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Description: Selected adverse events for this study included: 1) all infections, 2) serious infections, 3) potential opportunistic infections, 4) injection-related reactions (IRRs; an AE which occured within 24 hours after study treatment injection except where the event was not considered an allergic reaction), 5) psychiatric disorders and 6) anaphylaxis (an acute allergic/hypersensitivity reaction).

Measure: Number of Participants With Selected Adverse Events in the DB Period

Time: Up to Week 216

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Description: The Columbia-Suicide Severity Rating Scale (C-SSRS) is an assessment tool to evaluate suicidal ideation and behavior. Categories have binary responses (yes/no) and include: Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation or behavior is indicated by a "yes" answer to any of the listed categories. A score of 0 is assigned if no suicide risk is present. A score of 1 or higher indicates suicidal ideation or behavior.

Measure: Number of Participants With Suicidal Behaviors and Ideations Collected by Columbia-Suicide Severity Rating Scale in the DB Period

Time: Baseline and Post-Baseline (up to Week 216)

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Measure: Serum Satralizumab Concentration During the DB Period

Time: Baseline, Weeks 2, 4, 5, 6, 8, and every 4 weeks thereafter up to Week 204

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Measure: Serum Interleukin-6 (IL-6) Concentration During the DB Period

Time: Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 216

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Measure: Serum Soluble IL-6 Receptor (sIL-6R) Concentration During the DB Period

Time: Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 216

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Measure: Serum High Sensitivity C-Reactive Protein (hsCRP) Concentration During the DB Period

Time: Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 216

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Measure: Blood Anti-Aquaporin-4 (AQP4) Antibody Concentration Over Time

Time: Baseline, Weeks 2, 4, 8, 12, 24, 48, and every 24 weeks thereafter of double-blind period; every 24 weeks for first 48 weeks of open-label extension period (up to approximately 6.75 years)

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Measure: Percentage of Blood Plasmablasts Over Time

Time: Baseline, Weeks 2, 4, 8, 12, 24, 48, and every 24 weeks thereafter of double-blind period (up to approximately 38 months)

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Description: Reported here is the percentage of participants with at least one positive anti-drug antibody measurement during the DB period.

Measure: Percentage of Participants With Anti-Drug Antibodies to Satralizumab in the DB Period

Time: Up to approximately Week 216

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Primary Outcomes

Description: PET outcome measure

Measure: Standardized Uptake Value (SUV)/Standardized Uptake Value Ratio (SUVR)

Time: Baseline

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Secondary Outcomes

Description: Clinical outcome measure; Physical subscale range: 0-36; Cognitive subscale range: 0-40; Psychosocial subscale range: 0-8; Total MFIS Score scale range (Subscales Summed): 0-84; Higher values represent worse outcomes.

Measure: Modified Fatigue Impact Scale (MFIS)

Time: Baseline

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Description: PET outcome measure

Measure: Binding Potential (BPnd)

Time: Baseline

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Description: MRI outcome measure

Measure: MRI grey matter lesional load/brain atrophy

Time: Baseline

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Description: PET outcome measure

Measure: Tissue Volume of distribution (Vt)/Distribution Volume Ratios (DVR)

Time: Baseline

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Description: MRI outcome measure

Measure: MRI global/regional volumetrics

Time: Baseline

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Primary Outcomes

Description: Symbol Digit Modalities Test

Measure: Proportion of subjects with an increase in raw score of ≥ 4 points or 10% from baseline (improved)

Time: Up to approximately 3 years

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Secondary Outcomes

Description: Symbol Digit Modalities Test

Measure: Proportion of subjects with a decrease in raw score of ≥ 4 points or 10% from baseline (worsened)

Time: Up to approximately 3 years

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Description: Symbol Digit Modalities Test

Measure: Proportion of subjects with a raw score change from baseline who do not meet the improved or worsened definition (stable)

Time: Up to approximately 3 years

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Description: Symbol Digit Modalities Test

Measure: Proportion of subjects with an increase in raw score of ≥ 3 points from baseline

Time: Up to approximately 3 years

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Description: Symbol Digit Modalities Test

Measure: Proportion of subjects with a decrease in raw score of ≥ 3 points from baseline

Time: Up to approximately 3 years

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Description: The SDMT is a measure of cognitive processing speed

Measure: Change from baseline in Symbol Digit Modalities Test (SMDT)

Time: Up to approximately 3 years

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Description: Magnetic resonance imaging (MRI) brain volume

Measure: Percent change from baseline in thalamic, cortical grey matter, whole brain, lateral ventricular, and MOV volumes

Time: Up to approximately 3 years

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Description: Magnetic Resonance Imaging

Measure: Proportion of subjects free of gadolinium enhancing (GdE) lesions over 3 years

Time: Up to approximately 3 years

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Description: Magnetic Resonance Imaging

Measure: GdE lesion volume over 3 years

Time: Up to approximately 3 years

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Description: Magnetic Resonance Imaging

Measure: Number of unique new or enlarging hyperintense T2-weighted lesions and their volume from baseline to Year 3

Time: Up to approximately 3 years

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Description: Magnetic Resonance Imaging

Measure: Number of unique new or enlarging hypointense T1 weighted lesions and their volume from baseline to Year 3

Time: Up to approximately 3 years

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Description: Change is TSQM score over 3 years

Measure: Treatment Satisfaction Questionnaire for Medication (TSQM v1.4)

Time: Up to approximately 3 years

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Description: Change in WPAI score over 3 years

Measure: Work Productivity and Activity Impairment-Multiple Sclerosis (WPAI-MS)

Time: Up to approximately 3 years

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Description: The Fatigue Severity Scale (FSS) questionnaire contains nine statements that attempt to explore severity of fatigue symptoms.

Measure: Fatigue Severity Scale (FSS)

Time: Up to approximately 3 years

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Description: The MSQOL-54 is a multidimensional health-related QOL measure that combines both generic and MS-specific items into a single instrument

Measure: Multiple Sclerosis Quality of Life-54 (MSQOL-54)

Time: Up to approximately 3 years

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Description: The HADS was developed to identify anxiety disorders and depression among subjects in nonpsychiatric hospital clinics

Measure: Hospital Anxiety and Depression Scale (HADS)

Time: Up to approximately 3 years

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Description: Change in relapse rate over 3 years

Measure: Annualized relapse rate (ARR)

Time: Up to approximately 3 years

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Description: Disability progression assessed by 20% worsening from baseline over 3 years on T25W

Measure: Timed 25-foot Walk (T25W)

Time: Up to approximately 3 years

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Description: Change from baseline in the time in seconds needed to complete test activity

Measure: Nine-hole Peg Test (9-HPT)

Time: Up to approximately 3 years

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Description: Change from baseline in EDSS score (0-10) yearly and at 3 years

Measure: Expanded Disability Status Scale (EDSS)

Time: Up to approximately 3 years

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Description: An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre-existing condition) should be considered an AE.

Measure: Adverse Events (AEs)

Time: Up to approximately 3 years

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Primary Outcomes

Description: This will be calculated over whole brain, within white matter, within grey matter, and within MRI-visible lesions.

Measure: Tissue volume of Distribution (Vt)

Time: Through study completion, an average of 1 year

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Secondary Outcomes

Description: SUV will be calculated based on standard procedures.

Measure: Standardized uptake values (SUV)

Time: Through study completion, an average of 1 year

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Primary Outcomes

Description: Safety and tolerability

Measure: Part 1 and Part 2: Incidence of adverse events

Time: At 12 months after the first dose of study drug

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Measure: Part 1: Incidence of clinically significant changes in laboratory tests, electrocardiograms (ECGs), and vital signs

Time: At 12 months after the first dose of study drug

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Description: Dose assessment

Measure: Part 1: Recommended Part 2 dose of ATA188 monotherapy

Time: Day 1 to Day 35 of Cycle 1 for each participant in dose escalation part (approximately 1 year)

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Description: Antibody assessment and quantification

Measure: Part 2: Change from baseline in immunoglobulin G (IgG) index, including quantification of IgG production

Time: At 12 months after the first dose of study drug

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Secondary Outcomes

Description: Changes in disability score

Measure: Part 1: Change from baseline in expanded disability status scale (EDSS) score

Time: At 12 months after the first dose of study drug

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Description: Changes in disability score

Measure: Part 2: Change from baseline in clinical disability as assessed by the EDSS score and/or Timed 25 foot Walk (T25W) and/or 9-hole Peg Test (9HPT)

Time: At 12 months after the first dose of study drug

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Description: Change in MRI activity

Measure: Part 2: Change from baseline in cervical spinal cord volume and whole brain volume on MRI scans

Time: At 12 months after the first dose of study drug

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Description: Change in MRI activity

Measure: Part 2: Change from baseline in the number of Gadolinium-enhancing and new or enlarging T2 lesions on brain MRI scans

Time: At 12 months after the first dose of study drug

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