This is a Phase 3 extension, global, multicenter study to assess the long-term safety and tolerability of tolebrutinib in adult participants (aged ≥18 years) with RMS, PPMS, or NRSPMS who were previously enrolled in the Phase 2b LTS (LTS16004) or 1 of the 4 Phase 3 tolebrutinib pivotal trials (GEMINI 1 \[EFC16033\], GEMINI 2 \[EFC16034\], HERCULES \[EFC16645\], or PERSEUS \[EFC16035\]).
SUBSTUDY: ToleDYNAMIC substudy
Описание
Participants with relapsing MS from the Phase 2b LTS16004 parent study will continue open-label (OL) tolebrutinib.
All participants from the Phase 3 parent studies (EFC16033, EFC16034, EFC16645, and EFC16035) will learn which treatment they received in the parent study:
* If from one of the Phase 3 relapsing MS studies and on teriflunomide, an accelerated elimination procedure or a 3-month washout period is required prior to starting OL tolebrutinib. If on teriflunomide, and benefiting and recommended by the Investigator, the participant may opt to continue teriflunomide outside of the LTS17043 study, if clinically appropriate. If on tolebrutinib, the participant will continue tolebrutinib.
* All participants from one of the Phase 3 progressive MS studies will start OL tolebrutinib.
* If a participant already started OL tolebrutinib in the Phase 3 parent study this will be continued.
* RMS participants who are not eligible for OL tolebrutinib per Health Authority and/or ethics committee decisions on the study conduct (ie, partial hold on initiation of tolebrutinib) will continue their parent study treatment assignment as per their randomization from the parent study.
The treatment duration per participant will be approximately 3 years of OL tolebrutinib.
Кой може да участва
Inclusion Criteria:
\- 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.
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.
ToleDYNAMIC Substudy: Inclusion criteria are those of the main study
Exclusion Criteria:
* Participants are excluded from the study if any of the following criteria apply:
* 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
* 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
* Active alcohol use disorder or a history of alcohol or drug abuse within 1 year prior to the opt-in visit
* 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
* 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.
* 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.
* 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).
* Acute liver disease, cirrhosis, chronic liver disease (unless considered stable for more than 6 months).
* 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.
* 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.
NOTE: The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
ToleDYNAMIC Substudy: Exclusion criteria are those of the main study
Места на провеждане
43
Argentina (1)
Investigational Site Number : 0320002
CABA , Buenos Aires
Австралия (1)
Investigational Site Number : 0360001
St Leonards , New South Wales
Белгия (1)
Investigational Site Number : 0560005
Bruges
Бразилия (1)
HC UFG - Hospital Das Clinicas de Goias- Site Number : 0760003
Goiânia , Goiás
България (1)
Investigational Site Number : 1000002
Pleven
Канада (1)
Investigational Site Number : 1240002
Edmonton , Alberta
Chile (1)
Investigational Site Number : 1520002
Santiago , Reg Metropolitana de Santiago
Китай (1)
Investigational Site Number : 1560006
Beijing
Colombia (1)
Investigational Site Number : 1700001
Bogotá
Хърватия (1)
Investigational Site Number : 1910001
Zagreb
Чехия (1)
Investigational Site Number : 2039907
Brno
Дания (1)
Investigational Site Number : 2080001
Esbjerg
Estonia (1)
Investigational Site Number : 2330001
Tallinn
Финландия (1)
Investigational Site Number : 2460001
Tampere
Франция (1)
Investigational Site Number : 2500019
Besançon
Georgia (1)
Investigational Site Number : 2680004
Tbilisi
Гърция (1)
Investigational Site Number : 3000001
Athens
Hong Kong (1)
Investigational Site Number : 3440001
Shatin, NT
Унгария (1)
Investigational Site Number : 3489901
Budapest
Индия (1)
Investigational Site Number : 3560014
Bengaluru
Израел (1)
Investigational Site Number : 3760003
Haifa
Италия (1)
Investigational Site Number : 3800002
Pozzilli , Isernia
Япония (1)
Investigational Site Number : 3920016
Chiba , Chiba
Latvia (1)
Investigational Site Number : 4280002
Riga
Lithuania (1)
Investigational Site Number : 4400003
Kaunas
Mexico (1)
Investigational Site Number : 4840004
Guadalajara , Jalisco
Нидерландия (1)
Investigational Site Number : 5280001
Amsterdam
Норвегия (1)
Investigational Site Number : 5780003
Bergen
Полша (1)
Investigational Site Number : 6160008
Plewiska , Greater Poland Voivodeship
Puerto Rico (1)
San Juan MS Center- Site Number : 8400015
Guaynabo
Румъния (1)
Investigational Site Number : 6420015
Brasov
Сърбия (1)
Investigational Site Number : 6880001
Belgrade
Словакия (1)
Investigational Site Number : 7030001
Bratislava
South Africa (1)
Investigational Site Number : 7100001
Pretoria
Южна Корея (1)
Investigational Site Number : 4100001
Goyang-si , Gyeonggi-do
Испания (1)
Investigational Site Number : 7249908
A Coruña , A Coruña [La Coruña]
Швеция (1)
Investigational Site Number : 7520001
Gothenburg
Taiwan (1)
Investigational Site Number : 1580007
Hsinchu
Тайланд (1)
Investigational Site Number : 7640001
Bangkok Noi
Турция (1)
Investigational Site Number : 7920006
Ankara
Ukraine (1)
Investigational Site Number : 8040020
Chernivtsi
Великобритания (1)
Investigational Site Number : 8260003
Exeter , Devon
САЩ (1)
The University of Alabama at Birmingham- Site Number : 8400013