A Study to Evaluate the Efficacy and Safety of Remibrutinib in Secondary Progressive Multiple Sclerosis
- Conditions
- Secondary Progressive Multiple Sclerosis (SPMS)
- Interventions
- Registration Number
- NCT07225504
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
The purpose of this study is to provide efficacy and safety data for remibrutinib in patients with secondary progressive multiple sclerosis (SPMS)
- Detailed Description
This is a Phase III, randomized, double-blind, placebo-controlled, multi-center, parallel-group, event-driven study to evaluate the efficacy, safety and tolerability of remibrutinib in SPMS patients. Approximately 1275 eligible participants will be randomized to receive either remibrutinib or matching placebo.
The study consists of an event-driven Core Part with double-blind treatment, followed by an Extension Part with open-label remibrutinib treatment.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 1275
- Signed informed consent must be obtained prior to any assessment performed.
- Male or female participants aged 18-65 (inclusive) at Screening.
- Diagnosis of SPMS according to the 2017 revised McDonald criteria (Thompson et al 2018) at Screening.
- Absence of documented clinical relapses in the 24 months before Screening and randomization.
- EDSS score of 3.0 to 6.0 (inclusive) at Screening.
- Documented evidence of disability progression in the 12 months before Screening.
- Unwilling or unable to undergo MRI scans as per protocol (for example, claustrophobia, or presents absolute contraindications to MRI (e.g., metallic implants, metallic foreign bodies, pacemaker, defibrillator)).
- History of clinically significant central nervous system (CNS) disease (e.g. stroke, traumatic brain or spinal injury, history or presence of myelopathy) or neurological disorders which may mimic multiple sclerosis (MS).
- Ongoing substance abuse (drug or alcohol) or any other factor (e.g. serious psychiatric condition) that may interfere with the participant's ability to cooperate and comply with the study procedures.
- Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or neurological symptoms consistent with PML.
- Women of childbearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant from menarche until becoming post-menopausal, unless they are using highly effective methods of contraception (failure rate < 1% per year) while taking study treatment and for at least 1 week after stopping study treatment.
- Significant bleeding risk or coagulation disorders, at Screening.
- Use of exclusionary medication prior to Screening/randomization as listed in the protocol.
Other protocol-defined inclusion/exclusion critria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Remibrutinib (LOU064) Remibrutinib (blinded) Core Part: Remibrutinib film-coated tablet taken orally \[Extension Part: Open-label remibrutinib film-coated tablet taken orally\] Remibrutinib (LOU064) Remibrutinib (Open label) Core Part: Remibrutinib film-coated tablet taken orally \[Extension Part: Open-label remibrutinib film-coated tablet taken orally\] Placebo Placebo Core Part: Matching placebo film-coated tablet taken orally \[Extension Part: Open-label remibrutinib film-coated tablet taken orally\] Placebo Remibrutinib (Open label) Core Part: Matching placebo film-coated tablet taken orally \[Extension Part: Open-label remibrutinib film-coated tablet taken orally\]
- Primary Outcome Measures
Name Time Method Time to 6-month confirmed disability progression (6mCDP) on Expanded Disability Status Scale (EDSS) From baseline up to approximately 5 years The EDSS is an ordinal scale used for assessing neurologic impairment in MS based on a neurological examination. It consists of scores in each of seven functional systems and an ambulation score that are then combined to determine the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)).
6mCDP is defined as an increase from baseline in EDSS sustained for at least 6 months.
- Secondary Outcome Measures
Name Time Method Time to 3-month confirmed disability progression (3mCDP) on EDSS From baseline up to approximately 5 years The EDSS is an ordinal scale used for assessing neurologic impairment in MS based on a neurological examination. It consists of scores in each of seven functional systems and an ambulation score that are then combined to determine the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)).
3mCDP is defined as an increase from baseline in EDSS sustained for at least 3 months.Time to 6-month confirmed disability improvement (6mCDI) on EDSS From baseline up to approximately 5 years The EDSS is an ordinal scale used for assessing neurologic impairment in MS based on a neurological examination. It consists of scores in each of seven functional systems and an ambulation score that are then combined to determine the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)).
A 6mCDI is defined as a decrease from baseline in EDSS sustained for at least 6 months.Time to 3-month worsening by at least 20% in Timed 25-Foot Walk (T25FW) From baseline up to approximately 5 years The T25FW is an ambulation measurement assessing speed of walking: a timed (in seconds) walk of 25 feet (7.62 meters). Longer time indicates poorer lower limb function.
3-month worsening by at least 20% in T25FW is defined as an increase from baseline in T25FW of at least 20% sustained for at least 3 months.Time to 3-month worsening by at least 20% in 9-Hole Peg Test (9-HPT) From baseline up to approximately 5 years The 9-HPT is an objective quantitative test of neurological function. It is measured to assess both right and left arm scores, the metric is the time, in seconds, required to insert and remove 9 pegs. Longer time indicates poorer upper limb function.
A 3-month worsening by at least 20% in 9-HPT is defined as an increase from baseline in 9-HPT of at least 20% sustained for at least 3 monthsAnnualized rate of new or enlarging T2 lesions From baseline up to approximately 5 years Number of new or enlarging T2 lesions per year based on MRI
Annualized rate of brain atrophy From baseline up to approximately 5 years Percentage change in brain volume relative to baseline per year based on MRI assessments
Time to 6-month worsening by at least 4 points in Symbol Digit Modalities Test (SDMT) From baseline up to approximately 5 years The SDMT is a sensitive and specific test to assess information processing speed which is typically affected in cognitively impaired MS participants, The test scoring is calculated based on the number of correct answers in 90 seconds.
A 6-month worsening by at least 4 points in SDMT is defined as an increase from baseline in SDMT of at least 4 points sustained for at least 6 months.Number of participants with Adverse events and Serious adverse events (SAE) From baseline up to approximately 5 years Incidence of adverse events including changes in laboratory data, vital signs, electrocardiogram (ECG) and Columbia Suicide Severity Rating Scale (C-SSRS) qualifying and reported as AEs.