Eine klinische Studie zum Vergleich der Sicherheit und Wirksamkeit eines neuen Medikaments namens Fenebrutinib mit der des Standardmedikaments Ocrelizumab (Ocrevus®) bei erwachsenen Patienten mit primär progredienter multipler Sklerose (PPMS).

Product Name: FENEBRUTINIB
Product Code: [RO7010939]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: FENEBRUTINIB
Current Sponsor code: RO7010939
Other descriptive name: GDC-0853 RO7010939
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: OCREVUS
Product Name: OCRELIZUMAB
Product Code: [RO4964913]
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: OCRELIZUMAB
Current Sponsor code: RO4964913
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Concentrate for solution for injection/infusion
Route of administration of the placebo: Intravenous use

Gender:
Female: yes
Male: yes

Inclusion criteria:
? Age 46-65 years
? A diagnosis of PPMS in accordance to revised 2017 McDonald Criteria
? Disability progression in the 12 months prior to screening, as assessed by the Pre-Baseline Disability Progression Questionnaire
? Expanded Disability Status Scale (EDSS) score from 3.0 to 6.5 inclusive at screening
? Pyramidal functional subscore >=2 at screening
? For patients currently receiving proton pump inhibitors (PPIs) or H2-receptor antagonists (H2RAs): 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
? For patients requiring symptomatic treatment for MS and/or physiotherapy: treatment at a stable dose/regimen during the screening period prior to the initiation of study drug and plans to remain at a stable dose/regimen 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 women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for 6 or 12 months after the final dose of study medication
? For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm during the treatment period and for 28 days after the final dose of study medication to avoid exposing the embryo
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 946
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
? Gadolinium-enhancing lesions on T1-weighted magnetic resonance imaging (T1Gd+) lesion present on the screen MRI
? Any known or suspected active infection at screen or baseline,or any major episode of infection requiring hospitaliz or tx with IV anti-microbials
? Hx of confirmed or suspected progressive multifocal leukoencephalopathy
? Pt with a previous Hx of a serious IRR(CTCAE Grade >=4) and/or any hypersensitivity reaction to ocrelizumab
? Hx of cancer,including hematologic malignancy and solid tumors,within 10 years of screen
? Immunocompromised state
? Known presence of other neuro disorders
? Evidence of clinic signif cardiov,psychiatric,pulmonary,renal, hepatic,endocrine,metabolic,gastrointestinal (GI) disease that, in the PI opinion,would preclude pt participation
? Pt meeting the New York Heart Association Class III and Class IV criteria for congestive heart failure
? Screen 12-lead ECG that demonstrates clinic relevant abnormalities
? Current tx with medications that are well known to prolong the QT interval at doses that have a clinic meaningful effect on QT, as determined by the PI
? Hx of ventricular dysrhythmias or risk factors for ventricular dysrhythmias
? Any concomitant disease that may require chronic tx with systemic corticosteroids or immunosuppressants during the study
? Hx of alcohol or other drug abuse within 12 months prior to screen
? Pregnant or breastfeeding,or intending to become pregnant during the study or 6 or 12 months after final dose of study drug
? Men intending to father a child during the study or for 28 days after final dose of study drug
? + screen tests for active,latent,or inadequately treated hepatitis B
? + screen tests for hepatitis C
? Evidence of active or latent or inadequately treated infection with tuberculosis
? Hx of hospital or transfusion for a GI bleed
? Known bleeding diathesis
? Any condition possibly affecting oral drug absorption
? Hx of or currently active primary or secondary immunodeficiency
? Contraindications to mandatory pre-medications for IPRs
? Inability to complete an MRI scan
? Lack of peripheral venous access
? Any prev tx with bone marrow transplantation and hematopoietic stem cell transplantation
? Any prev Hx of transplantation or anti-rejection therapy
? Systemic corticosteroid therapy within 4 weeks prior to screen or during the screen period
? Tx with IV Ig or plasmapheresis within 12 weeks prior to RDM
? Sensitivity or intolerance to any ingredient of fenebrutinib or ocrelizumab
? Receipt of a live or live-attenuated vaccine within 6 weeks prior to RDM
? Need for systemic anti-coagulation (oral or injectable) or anti-platelet agent
? Prev tx with fenebrutinib or another Bruton's tyrosine kinase (BTK) inhibitor for any indication
? Tx with any investigational agent within 24 weeks prior to screen (Visit 1) or 5 half-lives of the investigational drug (whichever is longer), or tx with any experimental procedure for MS
? Requirement for any prohibited concomitant medications
? Tx with strong CYP3A4 inhibitors,strong or moderate CYP3A4 inducers,within 7 days or 5 drug elimination half-lives(whichever is longer)prior to RDM
? Tx with CYP3A4 substrates with a narrow therapeutic window within 7 days or 5 drug elimination half-lives(whichever is longer)prior to RDM
? Prev use of an anti-CD20 therapy within 6 months of RDM
? Prev use of fingolimod, siponimod, or ozanimod within 8 weeks of RDM or ponesimod within 4 weeks of RDM
? Prev use of natalizumab within 6 mo