A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of RO7268489 as Add-on Therapy to Ocrelizumab, in Participants With Progressive Forms of Multiple Sclerosis (MS)

Time From Randomization to the First Occurrence of Composite Confirmed Disability Progression (cCPD) Confirmed for at Least 12 Weeks (cCDP12)

Timeframe: Up to approximately 110 weeks

Time from randomization to the first occurrence of cCDP12 according to at least one of the following 3 criteria: 1. 12-week confirmed disability progression (CDP12) 2. 12-week confirmed increase in Timed 25-Foot Walk Test (T25FWT) or 3. 12-week confirmed increase in 9-Hole Peg Test (9-HPT) The EDSS is a disability scale is based on a standard neurological examination that ranges in 0.5-point steps from 0 (normal) - 10 (death). T25FWT=time taken to walk 25 feet, typically measured in seconds. The longer it takes to walk, the higher score, which indicates deterioration. Lower times indicate better performance and greater mobility. In 9-HPT, participants are instructed to place pegs one by one into each of nine holes arranged in a board stabilized with a plastic nonslip sheet on a solid table, and then to remove these pegs from the holes. The shorter time it takes to complete the task indicates a better outcome.

Time From Randomization to the First Occurrence of 24-Week Confirmed ≥4-Point Decrease (Worsening) in Symbol Digit Modalities Test (SDMT)

Timeframe: Up to approximately 110 weeks

The SDMT is a performance measure of processing speed that is widely used to assess cognitive function in response to treatment. It's brief, easy to administer, and involves a simple substitution task that healthy children and adults can easily perform. Using a reference key, the participant has 90 seconds to pair specific numbers with given geometric figures. The total SDMT score is the total number of correct responses and ranges from 0 to 110, with a higher score indicating a higher level of processing speed. A four-point change from baseline is typically considered clinically meaningful.

Change From Baseline in Total Brain Volume

Timeframe: Up to approximately 110 weeks

Time to Onset of 24-Week cCDP (cCDP24)

Timeframe: Up to approximately 110 weeks

Time to Onset of 12-Week Confirmed Disability Progression CDP (CDP12)

Timeframe: Up to approximately 110 weeks

Time to Onset of 24-Week CDP (CDP24)

Timeframe: Up to approximately 110 weeks

Time to ≥ 20% Increase in 12-week Confirmed Timed 25-Foot Walk Test (T25FWT)

Timeframe: Up to approximately 110 weeks

The time taken to walk 25 feet, typically measured in seconds. The longer it takes to walk, higher the score, which indicates deterioration and greater impairment. Lower times indicate better performance and greater mobility. Lower the mean change in the score over time, the better performance.

Time to ≥ 20% Increase in 24-week Confirmed T25FWT

Timeframe: Up to approximately 110 weeks

The time taken to walk 25 feet, typically measured in seconds. The longer it takes to walk, higher the score, which indicates deterioration and greater impairment. Lower times indicate better performance and greater mobility. Lower the mean change in the score over time, the better performance.

Time to ≥ 20% Increase in 12-week Confirmed 9-Hole Peg Test (9-HPT)

Timeframe: Up to approximately 110 weeks

Participants are instructed to place pegs one by one into each of nine holes arranged in a board stabilized with a plastic nonslip sheet on a solid table, and then to remove these pegs from the holes. Both the dominant and non-dominant hands are tested twice (two consecutive trials for each hand). The participants are required to complete two successful trials for each hand. The amount of time (in seconds) required to place and remove all nine pegs is recorded for each trial. More time = higher raw scores, which indicates deterioration. The lower mean change in the score over time, the better the performance.

Time to ≥ 20% Increase in 24-week Confirmed 9-HPT

Timeframe: Up to approximately 110 weeks

Participants are instructed to place pegs one by one into each of nine holes arranged in a board stabilized with a plastic nonslip sheet on a solid table, and then to remove these pegs from the holes. Both the dominant and non-dominant hands are tested twice (two consecutive trials for each hand). The participants are required to complete two successful trials for each hand. The amount of time (in seconds) required to place and remove all nine pegs is recorded for each trial. More time = higher raw scores, which indicates deterioration. The lower mean change in the score over time, the better the performance.

Plasma 2-arachidonoylglycerol (2-AG) Levels

Timeframe: Up to approximately 110 weeks

Change From Baseline in Plasma 2-AG Levels

Timeframe: Up to approximately 110 weeks

Number of Participants With Adverse events (AEs)

Timeframe: Up to 5 years

Number of Participants With Treatment Discontinuations due to AEs

Timeframe: Up to 5 years

Proportion of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)

Timeframe: Up to 5 years

C-SSRS is an assessment tool used to assess lifetime suicidality of participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, and attempts with actual/potential lethality. 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/behavior is indicated by a "yes" answer to any of the listed categories. Score of 0 is assigned if no suicide risk is present. Score of 1 or higher indicate suicidal ideation or behavior.

Plasma Concentrations of RO7268489 and Its Metabolite(s)

Timeframe: Up to 5 years