REMIBRUTINIB for Secondary progressive multiple sclerosis

Inclusion criteria

• {"criterion_text":"- Signed informed consent must be obtained prior to any assessment performed."}
• {"criterion_text":"- Male or female participants aged 18-65 (inclusive) at Screening."}
• {"criterion_text":"- Diagnosis of SPMS according to the 2017 revised McDonald criteria (Thompson et al 2018) at Screening."}
• {"criterion_text":"- Absence of documented clinical relapses in the 24 months before Screening and randomization."}
• {"criterion_text":"- EDSS score of 3.0 to 6.0 (inclusive) at Screening."}
• {"criterion_text":"- Documented evidence of disability progression in the 12 months before Screening."}

Exclusion criteria

• {"criterion_text":"- 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))."}
• {"criterion_text":"- History of clinically significant CNS disease (e.g. stroke, traumatic brain or spinal injury, history or presence of myelopathy) or neurological disorders which may mimic MS at Screening."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or neurological symptoms consistent with PML"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Significant bleeding risk or coagulation disorders, at Screening."}
• {"criterion_text":"- Use of exclusionary medication prior to Screening/randomization as listed in the protocol."}

Primary endpoints

• {"endpoint_text":"- Time to 6-month confirmed disability progression (6mCDP) on Expanded Disability Status Scale (EDSS)","definition_or_measurement_approach":"Time (from randomization) until confirmed disability progression sustained for 6 months, assessed using the Expanded Disability Status Scale (EDSS)."}

Secondary endpoints

• {"endpoint_text":"- Time to 3-month confirmed disability progression (3mCDP) on EDSS (key secondary)","definition_or_measurement_approach":"Time to confirmed disability progression sustained for 3 months assessed by EDSS."}
• {"endpoint_text":"- Time to 6-month confirmed disability improvement (6mCDI) on EDSS (key secondary)","definition_or_measurement_approach":"Time to confirmed disability improvement sustained for 6 months assessed by EDSS."}
• {"endpoint_text":"- Time to 3-month worsening by at least 20% in Timed 25-Foot Walk (T25FW) (key secondary)","definition_or_measurement_approach":"Time to a ≥20% worsening at 3 months in the Timed 25-Foot Walk test."}
• {"endpoint_text":"- Time to 3-month worsening by at least 20% in 9-Hole Peg Test (9-HPT) (key secondary)","definition_or_measurement_approach":"Time to a ≥20% worsening at 3 months in the 9-Hole Peg Test."}
• {"endpoint_text":"- Annualized rate of new or enlarging T2 lesions (key secondary)","definition_or_measurement_approach":"Annualized rate of new or enlarging T2 MRI lesions."}
• {"endpoint_text":"- Percentage of participants with annualized rate of brain atrophy > XX (key secondary)","definition_or_measurement_approach":"Proportion of participants exceeding a prespecified annualized brain atrophy threshold (threshold value 'XX' as specified in protocol)."}
• {"endpoint_text":"- Time to 6-month worsening by at least 4 points in Symbol Digit Modalities Test (SDMT)","definition_or_measurement_approach":"Time to confirmed worsening of ≥4 points on the SDMT sustained for 6 months."}
• {"endpoint_text":"- Adverse events, laboratory data, vital signs, electrocardiogram (ECG), Columbia Suicide Severity Rating Scale (C-SSRS)","definition_or_measurement_approach":"Safety assessments including recording of adverse events, labs, vital signs, ECGs and C-SSRS evaluations per protocol schedule."}

Methods

• K1 Recruitment Procedure Description (country-specific) documents present (e.g. 'K1_Recruitment Arrangements' / 'Recruitment Procedure Description') — channel: documented recruitment procedure provided for sites; targets: general public / potential participants; country-specific variants available (titles show multiple countries).
• K2 Advertisements (Posters, Flyers, Brochures, Flipcharts, Trifolds) — channel: printed/public-facing advertising materials; targets: potential participants/public; country-specific advertising packages available (document titles indicate country-specific versions for AT, BG, CZ, FR, DE, IT, RO, ES, PL, HR, EST, LV, LT, SI, SE, GR, BE, PT, SK, NL, HU, DK, IE).
• Patient-facing information and informed consent forms (L1_ICF) — channel: detailed participant information and consent documents provided in local languages; targets: prospective participants; country-specific ICFs and translations are present.
• Patient-facing PRO documents and patient cards (D4 / L1_Patient Card) — channel: participant materials to support engagement and retention; targets: enrolled participants (patient-facing).

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Parexel International (IRL) Limited

Responsibilities

codes:1,11,12,14,15 (Ancillary supplies),2,5,8

Name

IQVIA Limited

Responsibilities

code:1

Name

Icon Clinical Research Limited / Icon Laboratory Services Inc.

Responsibilities

code:1 / code:4

Name

Syneos Health Inc.

Responsibilities

code:1

Name

Eresearchtechnology Inc. (Clario)

Responsibilities

code:15 (ECOA and ECG)

Third parties

• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"codes:1,11,12,14,15 (Ancillary supplies),2,5,8","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"SGS France","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"code:1","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"code:1","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"code:15 (value: ECOA and ECG)","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"IQVIA RDS Hellas Single Member S.A.","duties_or_roles":"codes:1,15 (value: Start up CTA role actions)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Canada","full_name":"Neurorx Research Inc.","duties_or_roles":"code:15 (value: Imaging)","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"code:1","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Jumo Health USA Inc.","duties_or_roles":"code:15 (value: Patient recruitment and retention)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Austria","full_name":"Mag. Andreas Raffeiner GmbH","duties_or_roles":"code:8","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Medical Equipment Supplies And Management Limited","duties_or_roles":"code:15 (value: Ancillary supplies)","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Clinical Research / Eresearchtechnology (Clario) (as listed)","duties_or_roles":"various (e.g. ECOA and ECG listed under Eresearchtechnology)","organisation_type":"Pharmaceutical company / Laboratory service"}
• {"country":"Greece","full_name":"IQVIA RDS Hellas Single Member S.A. (regional IQVIA entity)","duties_or_roles":"codes:1,15 (Start up CTA role actions)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"code:15 (value: Travel Support)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc. / Clario (listed)","duties_or_roles":"code:15 (value: ECOA and ECG)","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Neurorx Research Inc. (Imaging)","duties_or_roles":"code:15 (value: Imaging)","organisation_type":"Pharmaceutical company"}