The primary purpose of the study is to evaluate the safety and tolerability of a single-ascending intravenous (IV) dose (Part 1), a single-ascending subcutaneous (SC) dose (Part 2), and multiple ascending SC doses (Part 3), and multiple-ascending SC doses following a single IV dose (Part 4) of RO7121932 in participants with multiple sclerosis (MS). Only Parts 1 and 2 of the study will be conducted in the United States, whereas Parts 1, 2, 3, and 4 will be conducted in all other participating countries outside the United States.
Expanded Disability Status Scale (EDSS) score ≤7.0 at Screening
Participants with relapsing multiple sclerosis (RMS) or progressive multiple sclerosis (PMS) who fulfil international panel criteria for diagnosis (McDonald 2017 criteria)
Participants not treated with any approved MS treatment at Screening and not planning to start on any MS therapy during the study (including follow-up)
Biological male and female participants
Evidence of clinical disease activity as defined by any clinical relapse within 3 months prior to screening, or by >1 clinical relapse within 12 months prior to screening
Evidence of brain magnetic resonance imaging (MRI) activity as defined by the presence of ≥ 1 Gadolinium (Gd)-enhancing T1 lesion in the screening MRI scan or by ≥ 4 new or enlarging T2 lesions in the screening scan as compared to a reference scan
Participants who have active progressive multifocal leukoencephalopathy (PML), have had confirmed PML, or have a high degree of suspicion for PML
Known presence of other neurological disorders that may mimic MS including but not limited to: neuromyelitis optica spectrum disease, Lyme disease, untreated Vitamin B12 deficiency, neurosarcoidosis, cerebrovascular disorders, and untreated hypothyroidism
Sequential
RO7121932 IV
DrugParticipants will receive RO7121932, as an IV infusion, per the schedule specified in the treatment arms.
RO7121932 SC
DrugParticipants will receive RO7121932, as SC injection, per the schedule specified in the treatment arms.
Parts 1, 2, 3, and 4: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) With Severity of AEs Measured According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5 (NCI CTCAE V5)
Parts 1, 2, 3, and 4: Change From Baseline in Suicide Risk as Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS)
The C-SSRS is an interview-based instrument used to assess baseline incidence of suicidal ideation (SI) and behavior. The assessment includes "yes" or "no" responses for 5 questions, each related to SI (wish to be dead, non-specific active suicidal thoughts, active SI with any methods, active SI with some intent, active SI with specific plan) and suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, suicide). Numeric ratings are provided for severity of ideation (if present), from 0 to 5. A score of 0 is assigned if no suicide risk is present. A score of 1 or higher indicates SI or behavior, with 5 being the most severe.
Parts 2 and 3: Percentage of Participants With Local Pain at the Site of Injection Assessed Using the Visual Analog Scale (VAS)
VAS is a 100 millimetre (mm) horizontal visual analog scale with values 0 to 100 mm to indicate pain. The following cutpoints on the VAS will be considered in the interpretation of the pain data: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm). A higher score indicates greater pain intensity.
Parts 2 and 3: Percentage of Participants With Local Injection-site Reaction Using Local Injection-site Symptom Assessment (LISSA)
LISSA form will be used to assess the participant's injection site for the following categories of reactions: Burning, Itching, Bruising, Erythema (redness), Hive formation, Induration, Swelling, Ecchymosis, Sensitivity, Papules, Stinging, Blister, Cold sensation, and Other. These reactions will be described using the following scale: Unable to assess, less than a dime (\<18 mm/\<0.7 inches), a dime (18 mm/0.7 inches), a nickel (21 mm/0.8 inches), a quarter (24 mm/1 inch), a half dollar (31 mm/1.2 inches), larger than a half dollar (\>31 mm/\>1.2 inches). A higher score indicates high injection site reactions.
Parts 1, 2 and 3 (Week 1 and Week 4): Time to Maximum Observed Concentration (Tmax) of RO7121932
Parts 1, 2 and 3 (Week 1 and Week 4): Maximum Observed Serum Concentration (Cmax) of RO7121932
Parts 1, 2 and 3 (Week 1 and Week 4): Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours (h) (AUC0-168h) Postdose
Parts 1 and 2: Area Under the Serum Concentration-time Curve up to the Last Measurable Concentration (AUClast)
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