TOLEBRUTINIB for Relapsing multiple sclerosis | Primary progressive multiple sclerosis | Secondary progressive multiple sclerosis

Inclusion criteria

• {"criterion_text":"- Participants with RMS, PPMS, or NRSPMS who completed the Phase 2b LTS (LTS16004) or 1 of the 4 Phase 3 pivotal tolebrutinib trials (EFC16033, EFC16034, EFC16645, EFC16035) on IMP.\n- OR - The Phase 2b LTS (LTS16004) or Phase 3 tolebrutinib pivotal trial participants who temporarily discontinued IMP due to a national emergency and completed the trial visits.\n- ToleDYNAMIC Substudy: Inclusion criteria are those of the main study"}

Exclusion criteria

• {"criterion_text":"- The participant is at risk for or has a persistent chronic, active (including fever higher than 38°C and clinically unstable), or recurring systemic infection, as judged by the Investigator\n- The participant is receiving treatment during the study period with drugs not permitted by the study protocol, including potent and moderate inducers of cytochrome P450 (CYP) 3A or potent inhibitors of CYP2C8 hepatic enzymes.\n- ToleDYNAMIC Substudy: Exclusion criteria are those of the main study\n- For participants initiating OL tolebrutinib in the LTS17043 study: Participants at risk of developing or having reactivation of hepatitis, ie, results at the unblinding visit (RMS) or opt-in visit (PMS) for serological markers for hepatitis B and C viruses indicating acute or chronic infection\n- Active alcohol use disorder or a history of alcohol or drug abuse within 1 year prior to the opt-in visit\n- Current alcohol intake equal to or exceeding the following at the opt-in visit: more than 2 drinks per day for men and more than 1 drink per day for women\n- Abnormal ECG during the opt-in visit considered in the Investigator’s judgment to be clinically significant, such as QTcF >500 msec, in the context of this study.\n- A bleeding disorder, known platelet dysfunction, abnormal platelet count (<100,000/microliter), history of significant bleeding event or other conditions and planned procedures that may predispose the participant to excessive bleeding during the study, as judged by the Investigator.\n- For participants initiating OL tolebrutinib in the LTS17043 study: Confirmed unblinding visit (RMS) or opt-in visit (PMS) alanine aminotransferase (ALT) more than 1.5 × upper limit of normal (ULN) OR aspartate aminotransferase (AST) more than 1.5 × ULN OR alkaline phosphatase more than 2 × ULN (unless caused by non-liver-related disorder or explained by a stable chronic liver disorder) OR total bilirubin more than 1.5 × ULN (unless due to Gilbert syndrome or non-liver-related disorder).\n- Acute liver disease, cirrhosis, chronic liver disease (unless considered stable for more than 6 months).\n- Participants who developed clinically relevant cardiovascular, hepatic, endocrine, neuropsychiatric or other major systemic disease making implementation of the protocol or interpretation of the trial results difficult or that would put the patient at risk by participating in the trial, as judged by the Investigator."}

Primary endpoints

• {"endpoint_text":"- Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) and AEs leading to permanent study intervention discontinuation","definition_or_measurement_approach":"Counting number of participants experiencing AEs, SAEs, AESIs and AEs that lead to permanent discontinuation of study intervention (safety/tolerability assessment)."}
• {"endpoint_text":"- Number of Participants with Potentially clinically significant abnormalities (PCSAs","definition_or_measurement_approach":"Counting number of participants with potentially clinically significant abnormalities (PCSA) detected during assessments."}

Secondary endpoints

• {"endpoint_text":"- Time to onset of 6-month confirmed disability worsening (CDW for RMS) or confirmed disability progression (CDP for PPMS and NRSPMS) for participants from pivotal studies","definition_or_measurement_approach":"Time-to-event analysis measuring time from baseline to first occurrence of 6-month confirmed disability worsening (RMS) or confirmed disability progression (PPMS/NRSPMS)."}
• {"endpoint_text":"- Annualized Relapse Rate (ARR) for RMS only","definition_or_measurement_approach":"Calculation of annualized relapse rate (number of relapses per participant-year) in participants with relapsing multiple sclerosis."}
• {"endpoint_text":"- Number of new and/or enlarging T2-hyperintense lesions per year","definition_or_measurement_approach":"MRI-based count of new and/or enlarging T2-hyperintense lesions per year."}
• {"endpoint_text":"- Change from baseline in total volume of T2-hyperintense lesions","definition_or_measurement_approach":"MRI volumetric measurement: change from baseline in total T2 lesion volume."}
• {"endpoint_text":"- ToleDYNAMIC substudy Change from baseline in biomarkers","definition_or_measurement_approach":"Laboratory biomarker measurements: change from baseline in specified biomarkers (ToleDYNAMIC substudy)."}

Primary sponsor

Full Name

Sanofi-Aventis Recherche & Developpement

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

ESMS Global Limited

Responsibilities

Centralized 24-Hour Emergency System: eSMS

Name

Icon Clinical Research Limited

Responsibilities

Home Health Care / Nursing

Name

Suvoda LLC

Responsibilities

sponsor duties code 3 (quality/clinical trial systems)

Name

Pharmalink Sp. z o.o.

Responsibilities

sponsor duties code 14

Name

Labcorp Central Laboratory Services S.a.r.l.

Responsibilities

central laboratory services (sponsor duties code 4)

Third parties

• {"country":"United Kingdom","full_name":"ESMS Global Limited","duties_or_roles":"Centralized 24-Hour Emergency System: eSMS","organisation_type":"Pharmaceutical company"}
• {"country":"Poland","full_name":"Pharmalink Sp. z o.o.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Poland","full_name":"Centrala Farmaceutyczna Cefarm S.A.","duties_or_roles":"Medical Device Management","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"Apoteket AB","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Alcura Health Espana S.A.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Hungary","full_name":"PetMobile Kft.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Home Health Care / Nursing","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Hungary","full_name":"Affidea Magyarorszag Kft.","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Greece","full_name":"Bioiatriki Private Medical Polyclinic S.A.","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Hungary","full_name":"Capital Medical Point Kft.","duties_or_roles":"Imaging","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Finland","full_name":"Oriola Finland Oy","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Depo-pack S.r.l.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Neurorx Research Inc.","duties_or_roles":"Central Medical Reading or Imaging Reading","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"Tamro AB","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Ashfield Iberia S.L.","duties_or_roles":"Home nursing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Koneksa Health Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Czechia","full_name":"PHOENIX lekarensky velkoobchod s.r.o.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}