A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Ocrelizumab in Adult Participants With Primary Progressive Multiple Sclerosis

Korábbi kezelés

• 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.
• 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.
• 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.
• Any previous treatment with cladribine, mitoxantrone, daclizumab, alemtuzumab, or cyclophosphamide
  • OLE Exclusion Criteria:

Más betegség

• 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).
• 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.
• Chronic liver disease unless considered stable for \>6 months
• Acute liver disease
• 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
• Chronic liver disease unless considered stable for \> 6 months
• Acute liver disease
• Gilbert's syndrome

Egyéb

• For participants enrolled in Germany and in Italy only: Presence of gadolinium-enhancing lesions on T1-weighted MRI (T1Gd +) lesion on the screening MRI
• Presence of cirrhosis (Child-Pugh Class A, B, or C)
• Lack of peripheral venous access.
• Cirrhosis (Child-pugh Class A, B or C)

• 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.
  • 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.