A Study to Investigate the Efficacy of Fenebrutinib in Relapsing Multiple Sclerosis (RMS)

Radiologic evaluation for Gd enhancing T1 lesion rate was performed using a standardized MRI protocol at screening, and at Weeks 4, 8, and 12. All MRI scans were read by a centralized reading center for efficacy endpoints. The total number of new Gd-enhancing T1 lesions were calculated as the sum of the individual number of new lesions observed at Weeks 4, 8 and 12. The lesion rate (new lesions per scan) was estimated from a negative binomial regression model for the total number of events and was adjusted for the covariate 'presence or absence of T1 Gd+ lesions on the screening MRI'. Log-transformed number of scans were included in the negative binomial model as an "offset" variable to account for different number of scans.

Radiologic evaluation for new or enlarging T2 - weighted lesion rate was performed using a standardized MRI protocol at screening, and at Weeks 4, 8, and 12. All MRI scans were read by a centralized reading center for efficacy endpoints. Total number of new or enlarging T2-weighted lesions were calculated as the sum of the individual number of new or enlarging lesions at Weeks 4, 8, and 12. The lesion rate (new/enlarging lesions per scan) was estimated from a negative binomial regression model for the total number of events and was adjusted for the covariate 'presence or absence of T1 Gd+ lesions on the screening MRI'. Log-transformed number of scans were included in the negative binomial model as an "offset" variable to account for different numbers of scans.

Radiologic evaluation for new Gd - enhancing T1 lesion and new or enlarging T2 - weighted lesions were performed using a standardized MRI protocol at screening, and at Weeks 4, 8, and 12. All MRI scans were read by a centralized reading center for efficacy endpoints. The total number of new Gd-enhancing T1 lesions and new or enlarging T2 - weighted lesions were calculated as the sum of the individual number of lesions observed at Weeks 4, 8 and 12. Analysis was performed using a logistic regression model performed on the status of both new T1 Gd+ lesion and new or enlarging T2-weighted lesions post-baseline (present or not) adjusted for the stratification factor(s) presence or absence of T1 Gd+ lesions on the screening MRI.

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity, is a congenital anomaly or birth defect.

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity, is a congenital anomaly or birth defect.

C-SSRS=assessment tool used to assess lifetime suicidality of a 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, & attempts with actual/potential lethality. Categories have binary responses (yes/no) & 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= suicidal ideation or behavior.

Radiologic evaluation for Gd enhancing T1 lesion rate was performed using a standardized MRI protocol at screening, and at Week 4. All MRI scans were read by a centralized reading center for efficacy endpoints. The lesion rate (new lesions per scan) was estimated from a negative binomial regression model for the total number of events and was adjusted for the covariate 'presence or absence of T1 Gd+ lesions on the screening MRI'. Log-transformed number of scans were included in the negative binomial model as an "offset" variable to account for different number of scans.

Radiologic evaluation for Gd enhancing T1 lesion rate was performed using a standardized MRI protocol at screening, and at Week 8. All MRI scans were read by a centralized reading center for efficacy endpoints. The lesion rate (new lesions per scan) was estimated from a negative binomial regression model for the total number of events and was adjusted for the covariate 'presence or absence of T1 Gd+ lesions on the screening MRI'. Log-transformed number of scans were included in the negative binomial model as an "offset" variable to account for different number of scans.

Radiologic evaluation for Gd enhancing T1 lesion rate was performed using a standardized MRI protocol at screening, and at Week 12. All MRI scans were read by a centralized reading center for efficacy endpoints. The lesion rate (new lesions per scan) was estimated from a negative binomial regression model for the total number of events and was adjusted for the covariate 'presence or absence of T1 Gd+ lesions on the screening MRI'. Log-transformed number of scans were included in the negative binomial model as an "offset" variable to account for different number of scans.

Radiologic evaluation for new or enlarging T2 - weighted lesion rate was performed using a standardized MRI protocol at screening, and at Week 4. All MRI scans were read by a centralized reading center for efficacy endpoints. The lesion rate (new/enlarging lesions per scan) was estimated from a negative binomial regression model for the total number of events and was adjusted for the covariate 'presence or absence of T1 Gd+ lesions on the screening MRI'. Log-transformed number of scans were included in the negative binomial model as an "offset" variable to account for different number of scans.

Radiologic evaluation for new or enlarging T2 - weighted lesion rate was performed using a standardized MRI protocol at screening, and at Week 8. All MRI scans were read by a centralized reading center for efficacy endpoints. The lesion rate (new/enlarging lesions per scan) was estimated from a negative binomial regression model for the total number of events and was adjusted for the covariate 'presence or absence of T1 Gd+ lesions on the screening MRI'. Log-transformed number of scans were included in the negative binomial model as an "offset" variable to account for different number of scans.

Radiologic evaluation for new or enlarging T2 - weighted lesion rate was performed using a standardized MRI protocol at screening, and at Week 12. All MRI scans were read by a centralized reading center for efficacy endpoints. The lesion rate (new/enlarging lesions per scan) was estimated from a negative binomial regression model for the total number of events and was adjusted for the covariate 'presence or absence of T1 Gd+ lesions on the screening MRI'. Log-transformed number of scans were included in the negative binomial model as an "offset" variable to account for different number of scans.