FREXALIMAB for Multiple sclerosis | Secondary progressive multiple sclerosis (non-relapsing)

Inclusion criteria

• {"criterion_text":"- Participant must have a previous diagnosis of RRMS in accordance with the 2017 revised McDonald criteria.\n- Participant must have a current diagnosis of SPMS in accordance with the clinical course criteria revised in 2013 endorsed by an Adjudication Committee.\n- Participant must have documented evidence of disability progression observed during the 12 months before screening. Eligibility will be analyzed by an Adjudication Committee.\n- Absence of clinical relapses for at least 24 months.\n- The participant must have an EDSS score at screening from 3.0 to 6.5 points, inclusive.\n- Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.\n- For patients eligible to be treated with siponimod: 1) does not tolerate it due to side effects or safety reasons, or 2) has failed siponimod treatment due to perceived lack of efficacy, or 3) has declined siponimod treatment."}

Exclusion criteria

• {"criterion_text":"- The participant has a history of infection or may be at risk for infection.\n- The presence of psychiatric disturbance or substance abuse.\n- History, clinical evidence, suspicion or significant risk for thromboembolic events, as well as myocardial infarction, stroke, and/or antiphosholipid syndrome and any participants requiring antithrombotic treatment.\n- History or current hypogammaglobulinemia defined by values below the lower limit of normal (LLN).\n- A history or presence of disease that can mimic MS symptoms, such as, but not limited to neuromyelitis optica spectrum disorder, systemic lupus erythematosus, Sjogren’s syndrome, acute disseminated encephalomyelitis, and myasthenia gravis.\n- The participant has sensitivity to any of the study interventions, or components thereof, or has a drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.\n- The participant was previously exposed to frexalimab."}

Primary endpoints

• {"endpoint_text":"- Time to onset of composite confirmed disability progression (cCDP) confirmed over 6 months","definition_or_measurement_approach":"Time-to-event: onset of composite confirmed disability progression (cCDP) confirmed over 6 months (as stated)"}

Secondary endpoints

• {"endpoint_text":"- Time to onset of composite cCDP confirmed over 3 months in the double-blind treatment period","definition_or_measurement_approach":"Time-to-event in double-blind treatment period; cCDP confirmed over 3 months (as stated)"}
• {"endpoint_text":"- Time to onset of CDP confirmed over 3-months or 6 months in the double-blind treatment period","definition_or_measurement_approach":"Time-to-event in double-blind treatment period; CDP confirmed over 3 or 6 months (as stated)"}
• {"endpoint_text":"- Time to onset of confirmed disability improvement (CDI) in the double-blind treatment period","definition_or_measurement_approach":"Time-to-event measurement of confirmed disability improvement during double-blind treatment period (as stated)"}
• {"endpoint_text":"- Number of new and/or enlarging T2 hyperintense lesions per scan as detected by MRI","definition_or_measurement_approach":"MRI-based count of new and/or enlarging T2 hyperintense lesions per scan (as stated)"}
• {"endpoint_text":"- Percent change in brain volume loss as detected by MRI scans at the end of double-blind treatment period compared to Month 6","definition_or_measurement_approach":"MRI-based percent change in brain volume loss comparing end of double-blind period to Month 6 (as stated)"}
• {"endpoint_text":"- Change in cognitive function at the end of double-blind treatment period compared to baseline as assessed by symbol digit modalities test (SDMT)","definition_or_measurement_approach":"Change from baseline in SDMT score at end of double-blind period (as stated)"}
• {"endpoint_text":"- Change from baseline in multiple sclerosis impact scale 29 version 2 (MSIS-29v2) questionnaire scores over time in the double-blind treatment period","definition_or_measurement_approach":"Patient-reported outcome change from baseline using MSIS-29v2 over time (as stated)"}
• {"endpoint_text":"- Change from baseline in patient reported outcome measurement information system (PROMIS) Fatigue multiple sclerosis (MS)-8a over time in the double-blind treatment period","definition_or_measurement_approach":"Patient-reported PROMIS Fatigue MS-8a score change from baseline over time (as stated)"}
• {"endpoint_text":"- Annualized relapse rate during the double-blind treatment period assessed by protocol defined adjudicated relapses","definition_or_measurement_approach":"Annualized relapse rate based on protocol-defined adjudicated relapses during double-blind period (as stated)"}
• {"endpoint_text":"- Adverse events, SAEs, AEs leading to permanent study intervention discontinuation, AESIs, and PCSAs in laboratory tests, ECG, and vital signs during the study period","definition_or_measurement_approach":"Safety assessments including AE/SAE counts, discontinuations, AESIs, and potentially clinically significant abnormalities in labs, ECG, and vitals (as stated)"}
• {"endpoint_text":"- Antidrug antibody over time","definition_or_measurement_approach":"Measurement of antidrug antibody presence/titers over time (as stated)"}
• {"endpoint_text":"- Change from baseline in serum Ig levels over time","definition_or_measurement_approach":"Change from baseline in serum immunoglobulin levels measured over time (as stated)"}
• {"endpoint_text":"- Change from baseline in plasma neurofilament light chain (NfL) levels over time in the double-blind treatment period","definition_or_measurement_approach":"Change from baseline in plasma NfL measured over time during the double-blind period (as stated)"}
• {"endpoint_text":"- Frexalimab plasma concentration over time in the double-blind treatment period","definition_or_measurement_approach":"Pharmacokinetic measurement: frexalimab plasma concentration over time during double-blind period (as stated)"}

Methods

• Digital marketing campaigns and digital marketing content (online ads/social media) targeting potential patients (documents: K2-recruitment-material-digital-marketing-campaign-content in multiple languages).
• Study landing pages / site webpages for patient information and recruitment (documents: K2-recruitment-material-landing-page in multiple languages).
• Posters and printed recruitment materials for distribution at clinical sites targeting potential participants (documents: K2-recruitment-material-poster in multiple languages).
• Patient brochures and patient guides for potential participants (documents: K2-recruitment-material-patient-brochure / -guide in multiple languages).
• Doctor-to-doctor referral letters and HCP-facing materials to encourage site referrals (documents: K2-recruitment-material-dr-to-dr-referral-letter and equivalents in multiple languages).
• Self-assessment questionnaires and pre-screening tools for patients (documents: K2-recruitment-material-self-assessment-questionnaire).
• Secondary assessment and communication pages/processes to triage referrals (documents: K2-recruitment-material-secondary-assessment-and-communication).
• Country- and language-specific recruitment arrangements (K1 recruitment arrangements and K2 materials provided in multiple country languages as listed in documents).

Primary sponsor

Full Name

Sanofi-Aventis Research & Development

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

ESMS Global Limited

Responsibilities

Centralized 24-Hour Emergency System: eSMS

Name

Neurorx Research Inc.

Responsibilities

Central Medical Reading or Imaging Reading

Name

Icon Clinical Research Limited

Responsibilities

Home Health Care / Nursing

Third parties

• {"country":"Romania","full_name":"Bioclinica S.A.","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Alcura Health Espana S.A.","duties_or_roles":"code:14","organisation_type":"Pharmaceutical company"}
• {"country":"Czechia","full_name":"PHOENIX lekarensky velkoobchod s.r.o.","duties_or_roles":"code:14","organisation_type":"Pharmaceutical company"}
• {"country":"Portugal","full_name":"Evidenze Portugal Unipessoal Lda.","duties_or_roles":"code:14","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"ESMS Global Limited","duties_or_roles":"code:15; value: Centralized 24-Hour Emergency System: eSMS","organisation_type":"Pharmaceutical company"}
• {"country":"Romania","full_name":"Alliance Healthcare Romania S.R.L.","duties_or_roles":"code:14","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Neurorx Research Inc.","duties_or_roles":"code:15; value: Central Medical Reading or Imaging Reading","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"Hungary","full_name":"PetMobile Kft.","duties_or_roles":"code:14","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Romania","full_name":"Affidea Romania S.R.L.","duties_or_roles":"code:4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"France","full_name":"Marken","duties_or_roles":"code:14","organisation_type":"Pharmaceutical company"}
• {"country":"Romania","full_name":"Medimar Imagistic Services S.R.L.","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"Romania","full_name":"Hiperdia S.A.","duties_or_roles":"code:4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"code:3","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"code:15; value: Home Health Care / Nursing","organisation_type":"Pharmaceutical company"}
• {"country":"Poland","full_name":"Centrala Farmaceutyczna Cefarm S.A.","duties_or_roles":"code:14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"code:7","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Depo-pack S.r.l.","duties_or_roles":"code:14","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Marken (duplicate entry in list may exist)","duties_or_roles":"code:14","organisation_type":"Pharmaceutical company"}
• {"country":"","full_name":"Other listed third-party service providers (various laboratory, packaging, distribution, imaging, home health and logistics providers)","duties_or_roles":"see individual entries above","organisation_type":"Various"}