Gender: All
Maximum age: 65 Years
Minimum age: 18 Years
Inclusion Criteria:
- For sites in Germany and Italy only, enrollment is restricted to participants aged
46-65 years
- A diagnosis of PPMS in accordance to the revised 2017 McDonald Criteria (Thompson et
al. 2018).
- Disability progression in the 12 months prior to screening.
- Expanded Disability Status Scale (EDSS) score from 3.0 to 6.5 inclusive at
screening.
- Pyramidal functional subscore >=2 at screening.
- For participants currently receiving proton pump inhibitors (PPIs), H2-receptor
antagonists (H2RAs), symptomatic treatment for MS (e.g. fampridine, cannabis) and/or
physiotherapy: treatment at a stable dose during the screening period prior to the
initiation of study treatment and plans to remain at a stable dose for the duration
of study treatment.
- Neurologically stable for at least 30 days prior to randomization and baseline
assessments.
- Ability to complete the 9-Hole Peg Test (9-HPT) for each hand in <240 seconds.
- Ability to perform Timed 25-Foot Walk Test (T25FWT) in <150 seconds.
- For female participants of childbearing potential: agreement to remain abstinent
(refrain from heterosexual intercourse) or use contraceptive measures, and refrain
from donating eggs.
- For male participants: agreement to remain abstinent (refrain from heterosexual
intercourse) or use contraceptive measures, and refrain from donating sperm.
Exclusion Criteria:
- For participants enrolled in Germany and in Italy only: Presence of
gadolinium-enhancing lesions on T1-weighted MRI (T1Gd +) lesion on the screening MRI
- Any known or suspected active infection (excluding onychomycosis) at screening,
including but not limited to a positive screening test for Hepatitis B and C, an
active or latent or inadequately treated infection with tuberculosis (TB), a
confirmed or suspected progressive multifocal leukoencephalopathy (PML).
- Participants with a previous history of a serious Infusion-Related Reaction (IRR)
(Common Terminology Criteria for Adverse Events [CTCAE] Grade >= 4) and/or any
hypersensitivity reaction to ocrelizumab.
- History of cancer including hematologic malignancy and solid tumors within 10 years
of screening. Exceptions: Basal/squamous cell carcinoma of skin cured by excision.
In situ carcinoma of the cervix successfully treated by curative therapy >1 year
prior to screening.
- Known presence of other neurological disorders, that could interfere with the
diagnosis of MS or assessments of efficacy or safety during the study, clinically
significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine,
metabolic or gastrointestinal disease.
- Presence of cirrhosis (Child-Pugh Class A, B, or C)
- Any concomitant disease that may require chronic treatment with systemic
corticosteroids, immunosuppressants or specific medication that could impact the
primary evaluation of the study.
- History of alcohol or other drug abuse within 12 months prior to screening.
- Female participants who are pregnant or breastfeeding or intending to become
pregnant during the study or 6 or 12 months (as applicable from the local label for
ocrelizumab) after final dose of study drug.
- Male participants intending to father a child during the study or for 28 days after
final dose of study drug.
- Lack of peripheral venous access.
- Any previous treatment with immunomodulatory or immunosuppressive medication without
an appropriate washout period.
- Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization.
- Immunocompromised state, history of primary or secondary (non-drug related)
immunodeficiency, or history of transplantation or antirejection therapy
- Known bleeding diathesis, anemia, or history of hospitalization or transfusion for
gastrointestinal (GI) bleed
- Any previous treatment with cladribine, mitoxantrone, daclizumab, alemtuzumab, or
cyclophosphamide
OLE Inclusion Criteria:
- Completed the Double-Blind Treatment (DBT) phase of the study (remaining on study
treatment; no other Disease-Modifying Therapy (DMT) administered) and who, in the
opinion of the investigator, may benefit from treatment with fenebrutinib.
- For female participants of childbearing potential: agreement to remain abstinent
(refrain from heterosexual intercourse) or use contraceptive measures, and refrain
from donating eggs.
- For male participants: agreement to remain abstinent (refrain from heterosexual
intercourse) or use contraceptive measures, and refrain from donating sperm.