Relapsing Multiple Sclerosis MedDRA version: 20.0 Level: PT Classification code 10048393 Term: Multiple sclerosis relapse System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.0 Level: PT Classification code 10080700 Term: Relapsing multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
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
Concentra
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Participants who are aged 18 to 55 years inclusive at the time of signing Informed Consent Form • A diagnosis of relapsing MS (RMS) in accordance with the revised 2017 McDonald Criteria and one of the following: o At least two documented clinical relapses within the last 2 years or one documented clinical relapse within 12 months of screening (but not within the 30 days prior to screening) o Documented evidence of the presence of at least one T1 Gd+ lesion on MRI in the 6 months prior to randomization (may include the screening MRI) • Expanded Disability Status Scale (EDSS) at screening from 0 to 5.5 points • For women of childbearing potential: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs during the treatment period and for 28 days after the final dose of fenebrutinib • For men: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm during the treatment period and for 28 days after the final dose of fenebrutinib 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 102 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Disease duration of >10 years from the onset of symptoms and an EDSS score at screening 1 year prior to screening is not exclusionary •Presence of other neurological disorders •Evidence of clinically significant psychiatric, pulmonary, renal, hepatic, metabolic, gastrointestinal (GI), or cardiovascular disease, or endocrine disease that, in the investigator’s opinion, would preclude patient participation •Presence of the New York Heart Association Class III and Class IV criteria for congestive heart failure •Screening 12-lead ECG that demonstrates clinically relevant abnormalities that may affect patient safety or interpretation of study results •Current treatment with medications that are well known to prolong the QT interval at doses that have a clinically meaningful effect on QT, as determined by the investigator •History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias •Participants undergoing dialysis or estimated glomerular filtration rate (eGFR) 2*upper limit of normal (ULN); Total bilirubin greater than 1.5*ULN; Hemoglobin <9.5 grams/deciliter; White blood cell count <2000 cells/mm^3 (µL); Platelet count <100*10^9/L; Absolute neutrophil count <=1500 cells/mm^3 (µL); IgG<500 mg/dL •Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the 12-week double-blind study period •History of alcohol or other drug abuse within 12 months prior to screening •Positive screening tests for active, latent, or inadequately treated hepatitis B •Positive screening tests for hepatitis C •Evidence of active or latent or inadequately treated infection with tuberculosis •Abnormalities in hepatic synthetic function tests judged by the investigator to be clinically significant •History of hospitalization 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 •Inability to complete an MRI scan or contraindication to Gd administration •Any previous history of organ transplantation •Any previous treatment with bone marrow transplantation or hematopoietic stem cell transplantation •Adrenocorticotropic hormone or systemic corticosteroid therapy within 4 weeks prior to screening or during the screening period •Receiving an unstable dosing regimen of proton pump inhibitors or H2-receptor antagonist during the screening phase and/or no plan to remain at a stable dose for the duration of study treatment •Treatment with IVIg or plasmapheresis within 12 weeks prior to randomization •Sensitivity or intolerance to any ingredient (including excipients) of fenebrutinib •Receipt of a live-attenuated vaccine within 6 weeks prior t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of fenebrutinib compared with placebo on the total number of new gadolinium enhancing T1 magnetic resonance imaging (MRI) lesions;Secondary Objective: • To evaluate the effect of fenebrutinib on MRI lesions • To evaluate the safety of fenebrutinib compared with placebo • To characterize the fenebrutinib pharmacokinetics (PK) profile;Primary end point(s): 1. Total number of new gadolinium-enhancing T1 lesions observed on MRI scans of the brain at Weeks 4, 8, and 12;Timepoint(s) of evaluation of this end point: 1. At Weeks 4, 8, and 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Total number of new or enlarging T2-weighted lesions observed on brain MRI at Weeks 4, 8, and 12 2.Proportion of participants free from any new gadolinium-enhancing T1 lesions and new or enlarging T2-weighted lesions observed on brain MRI at Weeks 4, 8, and 12 3.Incidence and severity of adverse events 4.Change from baseline in vital signs 5.Change from baseline in targeted clinical laboratory test results 6.Proportion of participants with suicidal ideation or behavior, as assessed by Columbia-Suicide Severity Rating Scale 7.Plasma concentration of fenebrutinib at specified timepoints;Timepoint(s) of evaluation of this end point: 1-2. At Weeks 4, 8, and 12 3. From the start of treatment until 28 days after the final dose of study treatment 4-5. Double blind period: Baseline (Day -28 to Day -1) to Week 12; Open label period: Baseline (Week 0) to Week 96 6. Double blind period: At Baseline (Day -28 to Day -1), Weeks 4, 8 and 12; Open label period: Baseline (Week 0), Weeks 12, 24, 48, 76 and 96 7. At Days 1, 29, 57, 85, at early discontinuation visit | — |
Countries
Croatia, Czechia, Czech Republic, Egypt, Japan, Kenya, Morocco, Norway, Serbia, Slovakia, Slovenia
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed