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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
119
Participants will receive RO7121932, as an IV infusion, per the schedule specified in the treatment arms.
Participants will receive RO7121932, as SC injection, per the schedule specified in the treatment arms.
Stanford University Medical Center
Stanford, California, United States
Yale University Multiple Sclerosis Center
New Haven, Connecticut, United States
Cliniques Universitaires St-Luc
Brussels, Belgium
UZ Gent
Ghent, Belgium
Montreal Neurological Institute and Hospital
Montreal, Quebec, Canada
Universitätsklinikum "Carl Gustav Carus"
Dresden, Germany
Universitätsmedizin Göttingen Georg-August-Universität
Göttingen, Germany
Klinikum rechts der Isar der TU Muenchen
München, Germany
Universitätsklinikum Münster Klinik u. Poliklinik f. Neurologie
Münster, Germany
Universitätsklinikum Tübingen, Zentrum für Neurologie
Tübingen, Germany
...and 16 more locations
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)
Time frame: Day 1 to Day 169 for Part 1 and Part 2; Day 1 to Day 197 for Part 3; Day 1 to Day 253 for Part 4
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.
Time frame: Day 1 to Day 169 for Part 1 and Part 2; Day 1 to Day 197 for Part 3; Day 1 to Day 253 for Part 4
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.
Time frame: Day 1, 2, 5, 8 for Part 2; Day 1, 2, 5, 8, 15, 22, 29, 36 for Part 3
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.
Time frame: Day 1,2, 5, 8 for Part 2; Day 1, 2, 5, 8, 15, 22, 29, 36 for Part 3
Part 4: Percentage of Participants With Local Injection-site Reactions
Time frame: Day 1 to Day 253
Parts 1, 2 and 3 (Week 1 and Week 4): Time to Maximum Observed Concentration (Tmax) of RO7121932
Time frame: Day 1 to Day 169 for Part 1 and Part 2; Days 1, 2, 5 and, 22 for Part 3
Parts 1, 2 and 3 (Week 1 and Week 4): Maximum Observed Serum Concentration (Cmax) of RO7121932
Time frame: Day 1 to Day 169 for Part 1 and Part 2; Days 1, 2, 5 and, 22 for Part 3
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
Time frame: Day 1 (predose) to Day 8 (168 hours post-dose) for Parts 1, 2, and 3 (Week 1) and Day 22 (predose) to Day 29 (168 hours post-dose) for Part 3 (Week 4)
Parts 1 and 2: Area Under the Serum Concentration-time Curve up to the Last Measurable Concentration (AUClast)
Time frame: Day 1 to Day 169 for Part 1 and Part 2
Parts 1 and 2: AUC From Time 0 to Infinity (AUCinf)
Time frame: Day 1 to Day 169 for Part 1 and Part 2
Part 1: Total Body Clearance (CL) Of RO7121932
Time frame: Day 1 to Day 169
Parts 2 and 3 (Week 4): Apparent Clearance (CL/F) of RO7121932
Time frame: Day 1 to Day 169 for Part 2; Day 22 to Day 29 for Part 3
Parts 1, 2 and 3: Terminal Rate Constant of RO7121932
Time frame: Day 1 to Day 169 for Part 1 and Part 2; Day 22 to Day 197 for Part 3
Parts 1, 2 and 3: Apparent Terminal Half-Life (T1/2) of RO7121932
Time frame: Day 1 to Day 169 for Part 1 and Part 2; Day 22 to Day 197 for Part 3
Part 3: Trough Concentrations (Ctrough) of RO7121932
Time frame: Day 1 to Day 197
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Part 3 (Week 1 and Week 4): Area Under the Concentration-time Curve Over One Dosing Interval (AUCtau) of RO7121932
Time frame: Day 1, 2, 5 and 22
Part 4: Serum Concentrations of RO7121932
Time frame: Day 1 to Day 253
Parts 1, 3 and 4: Cerebrospinal Fluid (CSF) Concentration of RO7121932
Time frame: Screening, Day 2 to Day 169 for Part 1; Screening, Day 2 to Day 197 for Part 3; Screening, Day 85 and Day 169 for Part 4
Parts 1, 2, 3 and 4: Percentage of Participants With Anti-RO7121932 Antibodies
Time frame: Days 1, 8, 22, 29, 57, 85,169 for Part 1; Days 1, 8, 22, 57, 85, 169 for Part 2; Days 1, 8, 15, 22, 29, 57, 85, 120 & 197 for Part 3; Days 1 to 253 for Part 4
Parts 1, 2, 3, and 4: Time Course of B-cell Frequencies in Blood
Time frame: Screening, Days 1, 2, 8, 22, 57, 85, 169 for Part 1; Screening, Days 1, 2, 8, 22, 57, 85, 169 for Part 2; Screening, Days 1, 2, 8, 15, 22, 57, 85, 120, 197 for Part 3; Screening up to Day 253 for Part 4
Parts 1 and 4: Time Course of B-cell Frequencies in CSF
Time frame: Screening, Day 2 to 169; Screening, Day 85 and Day 169 for Part 4
Parts 1, 2, 3, and 4: Change From Baseline in B-cell Frequencies in Blood
Time frame: Screening, Days 1, 2, 8, 22, 57, 85, 169 for Part 1; Screening, Days 1, 2, 8, 22, 57, 85, 169 for Part 2; Screening, Days 1, 2, 8, 15, 22, 57, 85, 120, 197 for Part 3; Screening up to Day 253 for Part 4
Parts 1, 3 and 4: Change From Baseline in B-cell Frequencies in CSF
Time frame: Screening, Day 2 to 169 for Part 1; Screening, Day 2 to 197 for Part 3; Screening, Day 85 and Day 169 for Part 4