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
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 infusion
INN or Proposed INN: Ocrelizumab
Current Sponsor code: RO4964913
Other descriptive name: OCRELIZUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Gender:
Female: yes
Male: yes

Inclusion criteria:
? Age 18-65 years inclusive at time of signing Informed Consent Form
? Ability to comply with the study protocol
? A diagnosis of PPMS in accordance to the revised 2017 McDonald Criteria
? EDSS score from 3.0 to 6.5 inclusive 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 (e.g., fampridine, cannabis) 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 HPT for each hand in < 240 seconds
? Ability to perform T25FWT
? 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 (as applicable by the local label for ocrelizumab) after the final dose of study medication. Women must refrain from donating eggs during this same period.
? For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm as defined below:
o With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 28 days after the final dose of study medication to avoid exposing the embryo. Men must refrain from donating sperm during this same period.
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 0

Exclusion criteria:
? Any known or suspected active infection at screening or baseline, or any major episode of infection requiring hospitalization or treatment with IV anti-microbials within 8 weeks prior to and during screening or treatment with oral anti-microbials within 2 weeks prior to and during screening
? History of confirmed or suspected progressive multifocal leukoencephalopathy (PML)
? Patients with a previous history of a serious IRR and/or any hypersensitivity reaction to ocrelizumab
? History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening
? Immunocompromised state
? Known presence of other neurological disorders
? Evidence of clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, or gastrointestinal (GI) disease that, in the investigator?s opinion, would preclude patient participation
? Patients meeting the New York Heart Association Class III and Class IV criteria for congestive heart failure
? Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
? History of alcohol or other drug abuse within 12 months prior to screening
? Positive screening tests for active, latent, or inadequately treated hepatitis B and hepatitis C (positive hepatitis C antibodies)
? Evidence of active or latent or inadequately treated infection with tuberculosis (TB)
? Abnormalities in hepatic synthetic function tests (e.g., PT, INR, PTT, albumin) judged by the investigator to be clinically significant
? History of hospitalizations or transfusion for a GI bleed
? Known bleeding diathesis
? Any condition possibly affecting oral drug absorption
? History of or currently active primary or secondary (non-drug related) immunodeficiency, including known history of HIV infection or IgG < 500 mg/dL
? Contraindications to mandatory premedications
? Inability to complete an MRI scan or contraindication to gadolinium administration
? Lack of peripheral venous access
? Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
? Any previous history of transplantation or anti rejection therapy
? Systemic corticosteroid therapy within 4 weeks prior to screening
? Treatment with IV Ig or plasmapheresis within 12 weeks prior to randomization
? Sensitivity or intolerance to any ingredient (including excipients) of fenebrutinib or ocrelizumab
? Receipt of a live or live attenuated vaccine within 6 weeks prior to randomization
? Need for systemic anticoagulation (oral or injectable) or anti platelet agent other than nonsteroidal anti inflammatory drugs, aspirin, and other salicylates (aspirin up to 162 mg once daily is allowed)
? Previous treatment with fenebrutinib or another BTK inhibitor for any indication
? Treatment with any investigational agent (including high dose biotin) within 24 weeks prior to screening (Visit 1) or 5 half lives of the investigational drug (whichever is longer), or treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency)
? Treatment with strong CYP3A4 inhibitors, strong or moderate CYP3A4 inducers, within 7 days or 5 drug elimination half-lives (whichever is longer) prior to randomization
? Treatment with CYP3A4 substrates with a narrow therapeutic window within 7 days or 5 drug elimination half-lives (whichever is longer) prior to randomization
? Previous use of anti-CD20s, including