Trial Outcomes & Findings for A Study to Investigate the Efficacy of Fenebrutinib in Relapsing Multiple Sclerosis (RMS) (NCT NCT05119569)

NCT ID: NCT05119569

Last Updated: 2025-11-10

Results Overview

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.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2
• Target enrollment: 109 participants
• Primary outcome timeframe: MRI scans performed at Weeks 4, 8 and 12
• Results posted on: 2025-11-10

Participant Flow

Participants were enrolled across 18 sites in 6 countries (Bosnia and Herzegovina, Croatia, Czech Republic, Serbia, Slovakia, and the United States). This study is still ongoing.

This study consists of two parts: Double-blind treatment (DBT) phase and an optional Open-label extension (OLE) phase. A total of 129 participants were screened, of which 109 were randomized into the fenebrutinib arm and placebo arm in a 2:1 ratio.

Participant milestones

Measure	DBT Phase: Fenebrutinib Participants received fenebrutinib, 200 milligrams (mg), orally, twice daily (BID) for 12 weeks during the DBT phase.	DBT Phase: Placebo Participants received fenebrutinib matching placebo, orally, BID for 12 weeks during the DBT phase.	OLE Phase: Fenebrutinib From Fenebrutinib Participants who received fenebrutinib in the DBT phase were given an option to receive fenebrutinib, 200 mg, orally, BID up to a maximum of 192 weeks in the OLE phase.	OLE Phase: Fenebrutinib From Placebo Participants who received fenebrutinib matching placebo in the DBT phase were given an option receive fenebrutinib, 200 mg, orally, BID up to a maximum of 192 weeks in the OLE phase.
Double Blind Treatment Phase STARTED	73	36	0	0
Double Blind Treatment Phase COMPLETED	65	34	0	0
Double Blind Treatment Phase NOT COMPLETED	8	2	0	0
Open Label Extension Phase STARTED	0	0	65	34
Open Label Extension Phase COMPLETED	0	0	0	0
Open Label Extension Phase NOT COMPLETED	0	0	65	34

Reasons for withdrawal

Measure	DBT Phase: Fenebrutinib Participants received fenebrutinib, 200 milligrams (mg), orally, twice daily (BID) for 12 weeks during the DBT phase.	DBT Phase: Placebo Participants received fenebrutinib matching placebo, orally, BID for 12 weeks during the DBT phase.	OLE Phase: Fenebrutinib From Fenebrutinib Participants who received fenebrutinib in the DBT phase were given an option to receive fenebrutinib, 200 mg, orally, BID up to a maximum of 192 weeks in the OLE phase.	OLE Phase: Fenebrutinib From Placebo Participants who received fenebrutinib matching placebo in the DBT phase were given an option receive fenebrutinib, 200 mg, orally, BID up to a maximum of 192 weeks in the OLE phase.
Double Blind Treatment Phase Withdrawal by Subject	2	2	0	0
Double Blind Treatment Phase Adverse Event	6	0	0	0
Open Label Extension Phase Ongoing in the study	0	0	65	34

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	DBT Phase: Fenebrutinib n=73 Participants Participants received fenebrutinib, 200 mg, orally, BID for 12 weeks during the DBT phase.	DBT Phase: Placebo n=36 Participants Participants received fenebrutinib matching placebo, orally, BID for 12 weeks during the DBT phase.	Total n=109 Participants Total of all reporting groups
Age, Continuous	38.6 years STANDARD_DEVIATION 8.5 • n=5 Participants	39.8 years STANDARD_DEVIATION 7.7 • n=20 Participants	39.0 years STANDARD_DEVIATION 8.2 • n=40 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	26 Participants n=20 Participants	78 Participants n=40 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	10 Participants n=20 Participants	31 Participants n=40 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	72 Participants n=5 Participants	36 Participants n=20 Participants	108 Participants n=40 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=20 Participants	1 Participants n=40 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) White	73 Participants n=5 Participants	36 Participants n=20 Participants	109 Participants n=40 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants

PRIMARY outcome

Timeframe: MRI scans performed at Weeks 4, 8 and 12

Population: All Randomized Participants set included all randomized participants grouped by treatment as assigned by randomization. Overall number analyzed is the number of participants with evaluable post-baseline MRI scans.

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.

Outcome measures

Measure	DBT Phase: Fenebrutinib n=70 Participants Participants received fenebrutinib, 200 mg, orally, BID for 12 weeks during the DBT phase.	DBT Phase: Placebo n=36 Participants Participants received fenebrutinib matching placebo, orally, BID for 12 weeks during the DBT phase.
DBT Phase: New Gadolinium (Gd) - Enhancing T1 Lesion Rate Observed on Magnetic Resonance Imaging (MRI) Scans of the Brain Over 12 Weeks	0.077 adjusted number of new lesions per scan Interval 0.043 to 0.135	0.245 adjusted number of new lesions per scan Interval 0.144 to 0.418

SECONDARY outcome

Timeframe: MRI scans performed at Weeks 4, 8 and 12

Population: All Randomized Participants set included all randomized participants grouped by treatment as assigned by randomization. Overall number analyzed is the number of participants with evaluable post-baseline MRI 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.

Outcome measures

Measure	DBT Phase: Fenebrutinib n=70 Participants Participants received fenebrutinib, 200 mg, orally, BID for 12 weeks during the DBT phase.	DBT Phase: Placebo n=36 Participants Participants received fenebrutinib matching placebo, orally, BID for 12 weeks during the DBT phase.
DBT Phase: New or Enlarging T2 - Weighted Lesion Rate Observed on MRI Scans of the Brain Over 12 Weeks	0.168 adjusted number of new lesions per scan Interval 0.102 to 0.277	0.634 adjusted number of new lesions per scan Interval 0.375 to 1.071

SECONDARY outcome

Timeframe: MRI scans performed at Weeks 4, 8 and 12

Population: All Randomized Participants set included all randomized participants grouped by treatment as assigned by randomization. Overall number analyzed is the number of participants with evaluable post-baseline MRI 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.

Outcome measures

Measure	DBT Phase: Fenebrutinib n=70 Participants Participants received fenebrutinib, 200 mg, orally, BID for 12 weeks during the DBT phase.	DBT Phase: Placebo n=36 Participants Participants received fenebrutinib matching placebo, orally, BID for 12 weeks during the DBT phase.
DBT Phase: Proportion of Participants Free From Any New Gd - Enhancing T1 Lesions and New or Enlarging T2 - Weighted Lesions Observed on MRI Scans of the Brain Over 12 Weeks	72.9 proportion of participants	50.0 proportion of participants

SECONDARY outcome

Timeframe: Up to Week 12

Population: Safety population included all participants who received any study drug.

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.

Outcome measures

Measure	DBT Phase: Fenebrutinib n=73 Participants Participants received fenebrutinib, 200 mg, orally, BID for 12 weeks during the DBT phase.	DBT Phase: Placebo n=36 Participants Participants received fenebrutinib matching placebo, orally, BID for 12 weeks during the DBT phase.
DBT Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	28 Participants	12 Participants
DBT Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: OLE Baseline (DBT Week 12) up to Week 192

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Week 192

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Week 192

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: MRI scan performed at Week 4

Population: All Randomized Participants set included all randomized participants grouped by treatment as assigned by randomization. Overall number analyzed is the number of participants with evaluable post-baseline MRI scans.

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.

Outcome measures

Measure	DBT Phase: Fenebrutinib n=70 Participants Participants received fenebrutinib, 200 mg, orally, BID for 12 weeks during the DBT phase.	DBT Phase: Placebo n=36 Participants Participants received fenebrutinib matching placebo, orally, BID for 12 weeks during the DBT phase.
DBT Phase: New Gd - Enhancing T1 Lesion Rate Observed on MRI Scans of the Brain at Week 4	0.210 adjusted number of new lesions per scan Interval 0.115 to 0.382	0.269 adjusted number of new lesions per scan Interval 0.128 to 0.565

OTHER_PRE_SPECIFIED outcome

Timeframe: MRI scan performed at Week 8

Population: All Randomized Participants set included all randomized participants grouped by treatment as assigned by randomization. Overall number analyzed is the number of participants with evaluable post-baseline MRI 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.

Outcome measures

Measure	DBT Phase: Fenebrutinib n=67 Participants Participants received fenebrutinib, 200 mg, orally, BID for 12 weeks during the DBT phase.	DBT Phase: Placebo n=34 Participants Participants received fenebrutinib matching placebo, orally, BID for 12 weeks during the DBT phase.
DBT Phase: New Gd - Enhancing T1 Lesion Rate Observed on MRI Scans of the Brain at Week 8	0.025 adjusted number of new lesions per scan Interval 0.006 to 0.101	0.325 adjusted number of new lesions per scan Interval 0.15 to 0.702

OTHER_PRE_SPECIFIED outcome

Timeframe: MRI scan performed at Week 12

Population: All Randomized Participants set included all randomized participants grouped by treatment as assigned by randomization. Overall number analyzed is the number of participants with evaluable post-baseline MRI 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.

Outcome measures

Measure	DBT Phase: Fenebrutinib n=63 Participants Participants received fenebrutinib, 200 mg, orally, BID for 12 weeks during the DBT phase.	DBT Phase: Placebo n=33 Participants Participants received fenebrutinib matching placebo, orally, BID for 12 weeks during the DBT phase.
DBT Phase: New Gd - Enhancing T1 Lesion Rate Observed on MRI Scans of the Brain at Week 12	0.007 adjusted number of new lesions per scan Interval 0.001 to 0.052	0.066 adjusted number of new lesions per scan Interval 0.013 to 0.324

OTHER_PRE_SPECIFIED outcome

Timeframe: MRI scan performed at Week 4

Population: All Randomized Participants set included all randomized participants grouped by treatment as assigned by randomization. Overall number analyzed is the number of participants with evaluable post-baseline MRI 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.

Outcome measures

Measure	DBT Phase: Fenebrutinib n=70 Participants Participants received fenebrutinib, 200 mg, orally, BID for 12 weeks during the DBT phase.	DBT Phase: Placebo n=36 Participants Participants received fenebrutinib matching placebo, orally, BID for 12 weeks during the DBT phase.
DBT Phase: New or Enlarging T2 - Weighted Lesion Rate Observed on MRI Scans of the Brain at Week 4	0.456 adjusted number of new lesions per scan Interval 0.274 to 0.757	0.891 adjusted number of new lesions per scan Interval 0.49 to 1.62

OTHER_PRE_SPECIFIED outcome

Timeframe: MRI scan performed at Week 8

Population: All Randomized Participants set included all randomized participants grouped by treatment as assigned by randomization. Overall number analyzed is the number of participants with evaluable post-baseline MRI 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.

Outcome measures

Measure	DBT Phase: Fenebrutinib n=67 Participants Participants received fenebrutinib, 200 mg, orally, BID for 12 weeks during the DBT phase.	DBT Phase: Placebo n=34 Participants Participants received fenebrutinib matching placebo, orally, BID for 12 weeks during the DBT phase.
DBT Phase: New or Enlarging T2 - Weighted Lesion Rate Observed on MRI Scans of the Brain at Week 8	0.058 adjusted number of new lesions per scan Interval 0.023 to 0.144	0.549 adjusted number of new lesions per scan Interval 0.314 to 0.958

OTHER_PRE_SPECIFIED outcome

Timeframe: MRI scan performed at Week 12

Population: All Randomized Participants set included all randomized participants grouped by treatment as assigned by randomization. Overall number analyzed is the number of participants with evaluable post-baseline MRI 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.

Outcome measures

Measure	DBT Phase: Fenebrutinib n=63 Participants Participants received fenebrutinib, 200 mg, orally, BID for 12 weeks during the DBT phase.	DBT Phase: Placebo n=33 Participants Participants received fenebrutinib matching placebo, orally, BID for 12 weeks during the DBT phase.
DBT Phase: New or Enlarging T2 - Weighted Lesion Rate Observed on MRI Scans of the Brain at Week 12	0.015 adjusted number of new lesions per scan Interval 0.003 to 0.068	0.282 adjusted number of new lesions per scan Interval 0.135 to 0.586

Adverse Events

DBT Phase: Fenebrutinib

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

DBT Phase: Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	DBT Phase: Fenebrutinib n=73 participants at risk Participants received fenebrutinib, 200 mg, orally, BID for 12 weeks during the DBT phase.	DBT Phase: Placebo n=36 participants at risk Participants received fenebrutinib matching placebo, orally, BID for 12 weeks during the DBT phase.
Infections and infestations Urinary tract infection	5.5% 4/73 • Number of events 4 • Up to Week 12 Safety population included all participants who received any study drug. Data collected up to the primary completion date is reported here. Adverse events section will be updated one year after the study completion date.	5.6% 2/36 • Number of events 2 • Up to Week 12 Safety population included all participants who received any study drug. Data collected up to the primary completion date is reported here. Adverse events section will be updated one year after the study completion date.
Investigations Hepatic enzyme abnormal	5.5% 4/73 • Number of events 4 • Up to Week 12 Safety population included all participants who received any study drug. Data collected up to the primary completion date is reported here. Adverse events section will be updated one year after the study completion date.	0.00% 0/36 • Up to Week 12 Safety population included all participants who received any study drug. Data collected up to the primary completion date is reported here. Adverse events section will be updated one year after the study completion date.
Vascular disorders Hypertension	0.00% 0/73 • Up to Week 12 Safety population included all participants who received any study drug. Data collected up to the primary completion date is reported here. Adverse events section will be updated one year after the study completion date.	5.6% 2/36 • Number of events 2 • Up to Week 12 Safety population included all participants who received any study drug. Data collected up to the primary completion date is reported here. Adverse events section will be updated one year after the study completion date.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER