Resumen

Estudio para evaluar la eficacia y seguridad de fenebrutinib sobre la progresión de la discapacidad en participantes adultos con esclerosis múltiple primaria progresiva (EMPP). Todos los participantes elegibles serán aleatorizados 1:1 a fenebrutinib oral diario (y placebo) o a ocrelizumab intravenoso (IV) (y placebo) de forma ciega mediante un sistema de respuesta interactiva por voz o web (IxRS). Se inscribieron y reclutaron 985 participantes a nivel global. Los participantes que interrumpan el medicamento del estudio de forma temprana o que abandonen el estudio no serán reemplazados. La fase de extensión abierta (OLE) está condicionada a un resultado positivo de beneficio-riesgo en el análisis primario del estudio.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 65 YearsSexo: ALL

Criterios de inclusión

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.
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.

Criterios de exclusión

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)
Chronic liver disease unless considered stable for \>6 months
Acute liver disease
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
Chronic liver disease unless considered stable for \> 6 months
Acute liver disease

Intervenciones

drug

Fenebrutinib

Participants will receive fenebrutinib.

drug

Ocrelizumab

Participants will receive ocrelizumab.

drug

Placebo matched to ocrelizumab

Participants will receive ocrelizumab-matching placebo.

drug

Placebo matched to fenebrutinib

Participants will receive fenebrutinib-matching placebo

Ubicaciones

Centro de Especialidades Neurológicas y Rehabilitación - CENyR

Buenos Aires, Argentina

Focus CECIC

Buenos Aires, Argentina

Instituto Reumatológico Strusberg

Córdoba, Argentina

Fundacion Rosarina de Neurorehabilitacion

Rosario, Argentina

Centro de Investigaciones Médicas Tucuman

San Miguel, Argentina

Patrocinadores

PrincipalHoffmann-La Roche

Estudio de fase III, multicéntrico, aleatorizado, doble ciego, doble simulacro, de grupos paralelos para evaluar la eficacia y seguridad de fenebrutinib en comparación con ocrelizumab en pacientes adultos con esclerosis múltiple primaria progresiva.

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Fenebrutinib

Ocrelizumab

Placebo matched to ocrelizumab

Placebo matched to fenebrutinib

Ubicaciones

Centro de Especialidades Neurológicas y Rehabilitación - CENyR

Focus CECIC

Instituto Reumatológico Strusberg

Fundacion Rosarina de Neurorehabilitacion

Centro de Investigaciones Médicas Tucuman

Patrocinadores