A clinical study to compare the safety and efficacy of a new drug called Fenebrutinib with that of the standard drug Ocrelizumab (Ocrevus®) in adult patients with primary progressive multiple sclerosis (PPMS).

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Latvia, Lithuania, Mexico, New Zealand, Peru, Poland, Portugal, Romania, Russian Federation, South Africa, Spain, Switzerland, Turkey, Ukraine, United Kingdom, United States (ICTRP)

ID di studio ICTRP
EUCTR2019-003919-53 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
A PHASE III MULTICENTER, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, PARALLEL-GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF FENEBRUTINIB COMPARED WITH OCRELIZUMAB IN ADULT PATIENTS WITH PRIMARY PROGRESSIVE MULTIPLE SCLEROSIS (BASEC)

Titolo accademico
A PHASE III MULTICENTER, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, PARALLEL-GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF FENEBRUTINIB COMPARED WITH OCRELIZUMAB IN ADULT PATIENTS WITH PRIMARY PROGRESSIVE MULTIPLE SCLEROSIS - - (ICTRP)

Titolo pubblico
A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared with Ocrelizumab in Adult Patients with Primary Progressive Multiple Sclerosis (ICTRP)

Malattie studiate
Multiple sclerosis
MedDRA version: 21.1Level: PTClassification code 10063401Term: Primary progressive multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders;Therapeutic area: Diseases [C] - Immune System Diseases [C20] (ICTRP)

Intervento studiato

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

(ICTRP)

Tipo di studio
Interventional clinical trial of medicinal product (ICTRP)

Disegno dello studio
Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2 (ICTRP)

Criteri di inclusione/esclusione
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
(ICTRP)

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

Endpoint primari e secondari
Main Objective: ? To evaluate the efficacy of fenebrutinib compared with ocrelizumab in patients with primary progressive multiple sclerosis (PPMS) regardless of adherence to randomized treatment based on time to onset of composite 12-week confirmed disability progression (cCDP12);Secondary Objective: ? To evaluate the efficacy of fenebrutinib compared with ocrelizumab in patients with PPMS regardless of adherence to randomized treatment based on time to onset of composite 24-week CDP (cCDP24), time to onset of 12-week CDP (CDP12) and time to onset of 24-week CDP (CDP24)
? To evaluate the efficacy of fenebrutinib had patients not switched to post-CDP24 open-label ocrelizumab (PC-OCR)
? To evaluate the safety of fenebrutinib compared with ocrelizumab
? To characterize the fenebrutinib pharmacokinetic (PK) profile

;Primary end point(s): 1. Time to onset of composite 12-week confirmed disability progression (cCDP12);Timepoint(s) of evaluation of this end point: 1. Up to 4.7 years [estimated duration of Double-Blind Treatment (DBT)] (ICTRP)

Secondary end point(s): 1. Time to onset of composite 24 week CDP (cCDP24)
2. Time to onset of 12-week CDP (CDP12)
3. Time to onset of 24 week CDP (CDP24)
4. Percent change in total brain volume from Week 24 as assessed by MRI scan
5. Change from baseline in patient-reported physical impacts of MS (as measured by Multiple Sclerosis Impact Scale, 29-Item [MSIS-29] physical scale
6. Time to onset of 12 week confirmed 4 point worsening in Symbol Digit Modality Test (SDMT) score
7. The nature, frequency, timing, and severity of adverse events; serious adverse events; and adverse events leading to study treatment withdrawal
8. Change from baseline in targeted vital signs
9. Change from baseline in targeted ECG parameters
10. Change from baseline in clinical laboratory results following study treatment administration
11.Proportion of patients with suicidal ideation or behavior, as assessed by Columbia Suicide Severity Rating Scale (C-SSRS)
12.Plasma concentration of fenebrutinib at specified timepoints;Timepoint(s) of evaluation of this end point: 1-3. Up to 4.7 years (estimated duration of DBT)
4-5. At Week 120
6-11. Up to 4.7 years (estimated duration of DBT)
12. Week 0, 2, 12, 24, 48, 72, 96, 120, at treatment discontinuation or unscheduled visit
(ICTRP)

Data di registrazione
11.02.2022 (ICTRP)

Inclusione del primo partecipante
29.03.2022 (ICTRP)

Sponsor secondari
non disponibile

Contatti aggiuntivi
Trial Information Support Line-TISL, global.rochegenentechtrials@roche.com, 000000, F. Hoffmann-La Roche Ltd (ICTRP)

ID secondari
GN41791, NCT04544449, 2019-003919-53-FR (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-003919-53 (ICTRP)