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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1246-7768 | Registry Identifier | ICTRP | |
| 2020-000647-30 | EudraCT Number |
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Primary Objective:
To determine the efficacy of SAR442168 compared to placebo in delaying disability progression in NRSPMS
Secondary Objective:
To evaluate efficacy of SAR442168 compared to placebo on clinical endpoints, magnetic resonance imaging (MRI) lesions, cognitive performance, physical function, and quality of life To evaluate safety and tolerability of SAR442168 To evaluate population pharmacokinetics (PK) of SAR442168 and relevant metabolites in NRSPMS and its relationship to efficacy and safety To evaluate pharmacodynamics (PD) of SAR442168
This was an event-driven (6-month CDP) trial with a variable treatment duration (end-of-study [EOS] duration: up to approximately 47months).
Participants with 6-month confirmed disability progression (CDP) had an option to receive tolebrutinib in the open-label (OL).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SAR442168 | Experimental | 60 mg of oral SAR442168 once daily |
|
| Placebo | Placebo Comparator | Placebo tablet to match SAR442168 once daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tolebrutinib | Drug | Pharmaceutical form: Film-coated tablet Route of administration: Oral |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to Onset of 6-Month Confirmed Disability Progression (CDP) as Assessed by Expanded Disability Status Scale (EDSS) | The EDSS is a disability scale that assesses the following 7 functional domains: visual, brainstem, pyramidal [motor], cerebellar [coordination], sensory, cerebral, and bowel/bladder. The total EDSS ranges from 0 (normal) to 10 (death due to multiple sclerosis [MS]) (0.5 increments from 1-10; next increase after 0 is 1). Higher scores indicated increased disability. Time to onset of 6-month CDP was defined as the time from randomization to the onset of a sustained increase from baseline in EDSS score of >=1.0 point from the baseline EDSS score when the baseline score was <=5.0 or of >=0.5 points when the baseline EDSS score was >5.0 confirmed after a minimum 6-month interval. | Baseline (Day 1) up to approximately 47 months |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Onset of 3-month Confirmed Disability Progression as Assessed by Expanded Disability Status Scale | The EDSS is a disability scale that assesses the following 7 functional domains: visual, brainstem, pyramidal [motor], cerebellar [coordination], sensory, cerebral, and bowel/bladder. The total EDSS ranges from 0 (normal) to 10 (death due to MS) (0.5 increments from 1-10; next increase after 0 is 1). Higher scores indicated increased disability. Time to onset of 3-month CDP was defined as the time from randomization to the onset of a sustained increase from baseline in EDSS score (of >=1.0 point from the baseline EDSS score when the baseline score is <=5.0, of >=0.5 points when the baseline EDSS score is >5.0) confirmed after a minimum 3-month interval. The confirmation of 3-month CDP followed the same criteria as that of 6-month CDP. |
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Inclusion criteria :
Exclusion criteria:
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Sciences & Operations | Sanofi | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama MS Center-Site Number:8400013 | Birmingham | Alabama | 35233 | United States | ||
| Center for Neurology and Spine-Site Number:8400089 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40202696 | Derived | Fox RJ, Bar-Or A, Traboulsee A, Oreja-Guevara C, Giovannoni G, Vermersch P, Syed S, Li Y, Vargas WS, Turner TJ, Wallstroem E, Reich DS; HERCULES Trial Group. Tolebrutinib in Nonrelapsing Secondary Progressive Multiple Sclerosis. N Engl J Med. 2025 May 15;392(19):1883-1892. doi: 10.1056/NEJMoa2415988. Epub 2025 Apr 8. |
| Label | URL |
|---|---|
| EFC16645 Plain language Results Summary | View source |
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Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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A total of 1131 participants were randomized in this study in a 2:1 ratio to receive either tolebrutinib or matching placebo in the double-blind (DB) period. Participants with 6-month confirmed disability progression (CDP) were given the option to receive open-label (OL) tolebrutinib. This was an event-driven (6-month CDP) trial with a variable treatment duration (end-of-study [EOS] duration: up to approximately 47 months).
A total of 1438 participants were screened at 267 centers in 31 countries between 24-Sep-2020 and 02-Dec-2022, of which 307 were screen failures mainly due to not meeting eligibility criteria.
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| ID | Title | Description |
|---|---|---|
| FG000 | DB: Placebo | Participants received placebo matched to tolebrutinib orally once daily up to approximately 47 months. |
| FG001 | DB: Tolebrutinib 60 mg | Participants received tolebrutinib 60 mg tablet orally once daily up to approximately 47 months. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| DB Period |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 20, 2023 | Jun 3, 2025 |
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| Placebo to match Tolebrutinib | Drug | Pharmaceutical form: Film-coated tablet Route of administration: Oral |
|
| Baseline (Day 1) up to approximately 47 months |
| Mean Number of New and/or Enlarging T2-hyperintense Lesions Per Year | Magnetic resonance imaging (MRI) of the brain was performed to identify number of new and/or enlarging T2-hyperintense lesions defined as the sum of the individual number of new and/or enlarging T2 lesions from baseline up to and including the EOS visit. | Baseline (Day 1) up to approximately 47 months |
| Time to Onset of Sustained 20% Increase in the 9-hole Peg Test (HPT) for at Least 3 Months | The 9-HPT is a brief, standardized, quantitative test of upper extremity function and the time to complete the 9-HPT is used to assess a participant's manual dexterity and fine motor skills. A participant was asked to place the pegs into the holes and remove them with the dominant and non-dominant hand; two successful trials for each hand. The amount of time (in seconds) required to place and remove all nine pegs was recorded for each trial (ranging from 10 to 300 seconds). The mean time to test completion served for assessment of the participant's hand dexterity. Higher value indicated worse outcome. An increase of >20% from the baseline in the 9-HPT was considered meaningful worsening; time to onset of sustained 20% increase for at least 3 months is presented. | Baseline (Day 1) up to approximately 47 months |
| Time to Onset of Sustained 20% Increase in the Timed 25-foot Walk (T25-FW) for at Least 3 Months | The T25-FW test is a quantitative mobility and leg function performance test used to assess a participant's walking ability. A participant was directed to one end of a clearly marked 25-foot course and instructed to walk 25 feet as quickly as safely possible for 2 trials. The amount of time (in seconds) to walk 25 feet was recorded (ranging from 2.2 to 180 seconds). The mean walk time was used for assessment of the participant's walking ability. Higher value indicated worse outcome. An increase of >20% from the baseline in the T25-FW test was considered meaningful worsening; time to onset of sustained 20% increase for at least 3 months is presented. | Baseline (Day 1) up to approximately 47 months |
| Time to Onset of 6-month Confirmed Disability Improvement (CDI) as Assessed by Expanded Disability Status Scale | The EDSS is a disability scale that assesses the following 7 functional domains: visual, brainstem, pyramidal [motor], cerebellar [coordination], sensory, cerebral, and bowel/bladder. The total EDSS ranges from 0 (normal) to 10 (death due to MS) (0.5 increments from 1-10; next increase after 0 is 1). Higher scores indicated increased disability. CDI was defined as a >=1 point decrease in the EDSS score from baseline confirmed over at least 6 months. | Baseline (Day 1) up to approximately 47 months |
| Percent Change in Brain Volume at EOS Compared to Month 6 | MRI of the brain was performed to evaluate percent change in brain volume which is considered as a marker of the central nervous system degenerative process. Least squares (LS) mean is presented. | Month 6 to EOS (up to approximately 47 months) |
| Change From Baseline in Cognitive Function as Assessed by Symbol Digit Modalities Test (SDMT) at EOS | The SDMT is used to assess processing speed, divided attention, visual scanning, tracking and motor speed. It involves a simple substitution task using a reference key. The number of correct substitutions and number of items completed within a 90 second interval (maximum 110 seconds) are recorded. A decrease of 4 points from baseline on the SDMT is considered meaningful worsening. The score was the number of correctly coded items from 0-110 in 90 seconds; higher scores indicated better outcome. LS mean is presented. Baseline was defined as the last available value prior to the first dose of study intervention. | Baseline (Day 1) to EOS (up to approximately 47 months) |
| Change From Baseline in Cognitive Function as Assessed by California Verbal Learning Test Second Edition (CVLT-II) at EOS | The CVLT-II is a verbal learning and memory test consisting of recall and recognition of a list of 16 words. The list was read by the examiner, participants listened to the list and reported as many of the items as possible. For each assessment, 5 trials were completed. Standardized scores were used for analysis. The maximum possible score was 80 and a minimum was 0. A higher score indicated better recall meaning improved cognitive function. LS mean is presented. Baseline was defined as the last available value prior to the first dose of study intervention. | Baseline (Day 1) to EOS (up to approximately 47 months) |
| Change From Baseline in Multiple Sclerosis Quality of Life-54 (MSQoL-54) Questionnaire Score at EOS | MSQoL-54 is standardized instrument with generic and MS-specific items which generates 12 subscales & 2 single-item measures (satisfaction with sexual function [1 item] & change in health [1 item].12 subscales are as follows:a:physical health (10 items),b:health perceptions (5 items), c:energy (5 items),d:role limitation physical (4 items),e:sexual function (4 items),f:pain (3 items),g:social function (3 items),h:health distress (4 items),i:overall quality of life (2 items),j:emotional well-being (5 items),k:role limitations emotional (3 items) and l:cognitive function (4 items).Physical health composite score was calculated as weighted sum of 'a to h' subscales and mental health composite score was calculated as weighted sum of 'i to l' subscales mentioned above.Each composite score was transformed linearly to common 0 (worst) to 100 (best) score range;LS mean is presented.Higher score indicated improved QoL.Baseline:last available value prior to first dose of study intervention. | Baseline (Day 1) to EOS (up to approximately 47 months) |
| Number of Participants With Treatment-emergent Adverse Events (AEs), Treatment-emergent Serious AEs, Treatment-emergent AEs Leading to Permanent Study Intervention Discontinuation, and Treatment-emergent Adverse Events of Special Interest (AESIs) | An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. An AESI was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. TEAEs were defined as AEs that developed, worsened or became serious during the TE period. | From first dose of study intervention (Day 1) up to end of follow-up, up to approximately 47 months |
| Maximum Observed Plasma Concentration (Cmax) of Tolebrutinib and M2 Metabolite | Blood samples were collected at specified timepoints to assess Cmax of tolebrutinib and M2 metabolite using a population pharmacokinetics (PopPK) model. | 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12 |
| Time to Maximum Observed Plasma Concentration (Tmax) of Tolebrutinib and M2 Metabolite | Blood samples were collected at specified timepoints to assess Tmax of tolebrutinib and M2 metabolite using a PopPK model. | 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12 |
| Area Under the Plasma Concentration-time Curve Over the Last 24-hours Dosing Interval (AUC0-24) of Tolebrutinib and M2 Metabolite | Blood samples were collected at specified timepoints to assess AUC0-24 of tolebrutinib and M2 metabolite using a PopPK model. | 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12 |
| Change From Baseline in Plasma Neurofilament Light Chain (NfL) and Serum Chitinase-3 Like Protein-1 (Chi3L1) Levels at EOS | Blood samples were collected at specified timepoints to assess change from baseline in NfL and Chi3L1. Baseline was defined as the last available value prior to the first dose of study intervention. | Baseline (Day 1) to EOS (up to approximately 47 months) |
| Change From Baseline in Cluster of Differentiation (CD)19+ B Cells at EOS | Blood samples were collected at specified timepoints to assess change from baseline in CD19+ B cells. Baseline was defined as the last available value prior to the first dose of study intervention. | Baseline (Day 1) to EOS (up to approximately 47 months) |
| Change From Baseline in Serum Immunoglobulin (Ig) Levels at EOS | Blood samples were collected at specified timepoints to assess change from baseline in IgG and IgM levels. Baseline was defined as the last available value prior to the first dose of study intervention. | Baseline (Day 1) to EOS (up to approximately 47 months) |
| Phoenix |
| Arizona |
| 84018 |
| United States |
| Arcadia Neurology Center-Site Number:8400070 | Arcadia | California | 91006 | United States |
| UC San Diego ACTRI-Site Number:8400101 | La Jolla | California | 92037 | United States |
| Collaborative Neuroscience Research-Site Number:8400045 | Long Beach | California | 90806 | United States |
| Multiple Sclerosis Center-Site Number:8400143 | Los Angeles | California | 90033 | United States |
| University of San Francisco, Sandler Neurosciences Center-Site Number:8400137 | San Francisco | California | 94158 | United States |
| Harbor UCLA-Site Number:8400088 | Torrance | California | 90502 | United States |
| Regina Berkovich, MD, PhD-Site Number:8400059 | West Hollywood | California | 90048 | United States |
| Mountain Neurological Research Center, Inc.-Site Number:8400128 | Basalt | Colorado | 81621 | United States |
| University of Colorado-Site Number:8400012 | Denver | Colorado | 80262 | United States |
| Advanced Neurosciences Research-Site Number:8400025 | Fort Collins | Colorado | 80528 | United States |
| South Florida Neurology Associates-Site Number:8400029 | Boca Raton | Florida | 33487 | United States |
| Neurology Associates, PA-Site Number:8400004 | Maitland | Florida | 32761 | United States |
| Aqualane Clinical Research-Site Number:8400027 | Naples | Florida | 34105 | United States |
| Axiom Clinical Research of Florida-Site Number:8400001 | Tampa | Florida | 33609-4052 | United States |
| University of South Florida-Site Number:8400006 | Tampa | Florida | 33612 | United States |
| Meridian Clinical Research-Site Number:8400003 | Savannah | Georgia | 31406 | United States |
| Consultants In Neurology-Site Number:8400011 | Northbrook | Illinois | 60062 | United States |
| University of Kansas Medical Center-Site Number:8400023 | Kansas City | Kansas | 66160-7321 | United States |
| CHI Saint Joseph Medical Group Neurology-Site Number:8400110 | Lexington | Kentucky | 40509 | United States |
| Tufts Medical Center-Site Number:8400072 | Boston | Massachusetts | 02111 | United States |
| University of Massachusetts-Site Number:8400014 | Worcester | Massachusetts | 01655 | United States |
| Wayne State University-Site Number:8400046 | Detroit | Michigan | 48201 | United States |
| The Memorial Hospital-Site Number:8400033 | Owosso | Michigan | 48867 | United States |
| Minneapolis Clinic of Neurology-Site Number:8400051 | Minneapolis | Minnesota | 55422 | United States |
| Mayo Clinic-Site Number:8400111 | Rochester | Minnesota | 55905 | United States |
| Missouri Baptist Medical Center-Site Number:8400019 | St Louis | Missouri | 63131 | United States |
| Lou Ruvo Center for Brain Health-Site Number:8400117 | Las Vegas | Nevada | 89106 | United States |
| Holy Name Hospital-Site Number:8400104 | Teaneck | New Jersey | 07666 | United States |
| University of New Mexico-Site Number:8400032 | Albuquerque | New Mexico | 87131 | United States |
| Icahn School of Medicine at Mount Sinai (Department of Endoc-Site Number:8400038 | New York | New York | 10029-6501 | United States |
| Neurology Associates of Stony Brook-Site Number:8400042 | Stony Brook | New York | 11794 | United States |
| Meridian Clinical Research, LLC-Site Number:8400005 | Raleigh | North Carolina | 27607 | United States |
| Sanford Brain & Spine Center-Site Number:8400126 | Fargo | North Dakota | 58103 | United States |
| University Hospitals CMC-Site Number:8400083 | Cleveland | Ohio | 44106 | United States |
| Cleveland Clinic-Site Number:8400125 | Cleveland | Ohio | 44195 | United States |
| Optimed Research, LTD-Site Number:8400147 | Columbus | Ohio | 43235 | United States |
| Neurology Specialists-Site Number:8400002 | Dayton | Ohio | 45417 | United States |
| Columbus Neuroscience-Site Number:8400010 | Westerville | Ohio | 40382 | United States |
| Providence Multiple Sclerosis Center-Site Number:8400020 | Portland | Oregon | 97225 | United States |
| Perelman Center for Advanced Medicine-Site Number:8400142 | Philadelphia | Pennsylvania | 19104 | United States |
| Jefferson Neurology Associates-Site Number:8400016 | Philadelphia | Pennsylvania | 19107 | United States |
| Premier Neurology-Site Number:8400069 | Greer | South Carolina | 29650 | United States |
| Mountain View Clinical Research-Site Number:8400024 | Greer | South Carolina | 29651-1817 | United States |
| Neurology Clinic, PC-Site Number:8400087 | Cordova | Tennessee | 38018 | United States |
| Advanced Neuroscience Center-Site Number:8400035 | Franklin | Tennessee | 37064 | United States |
| Baylor College of Medicine-Site Number:8400136 | Houston | Texas | 77030 | United States |
| Neurology Center of San Antonio-Site Number:8400036 | San Antonio | Texas | 78258 | United States |
| University Of Vermont College Of Medicine-Site Number:8400130 | Burlington | Vermont | 05401 | United States |
| Medical College of Wisconsin-Site Number:8400028 | Milwaukee | Wisconsin | 53226 | United States |
| Investigational Site Number :0320002 | Capital Federal | Buenos Aires | 1012 | Argentina |
| Investigational Site Number :0320001 | CABA | Buenos Aires F.D. | C1061 | Argentina |
| Investigational Site Number :0320007 | Buenos Aires | 1860 | Argentina |
| Investigational Site Number :0320006 | Córdoba | 5000 | Argentina |
| Investigational Site Number :0320005 | San Miguel de Tucumán | T4000AXL | Argentina |
| Investigational Site Number : 0360007 | St Leonards | New South Wales | 2065 | Australia |
| Investigational Site Number :0360003 | Woolloongabba | Queensland | 4102 | Australia |
| Investigational Site Number :0360002 | Kent Town | South Australia | Australia |
| Investigational Site Number :0360004 | Hobart | Tasmania | 7001 | Australia |
| Investigational Site Number :0360001 | Fitzroy | Victoria | 3065 | Australia |
| Investigational Site Number :0360006 | Heidelberg West | Victoria | 3081 | Australia |
| Investigational Site Number :0400003 | Innsbruck | 6020 | Austria |
| Investigational Site Number :0400001 | Linz | 4020 | Austria |
| Investigational Site Number :0400004 | Linz | 4021 | Austria |
| Investigational Site Number :0400002 | Vienna | 1090 | Austria |
| Investigational Site Number :1120004 | Vitebsk | 210009 | Belarus |
| Investigational Site Number :1120005 | Vitebsk | 210037 | Belarus |
| Investigational Site Number : 0560009 | Brussels | 1070 | Belgium |
| Investigational Site Number :0560007 | Brussels | 1200 | Belgium |
| Investigational Site Number :0560003 | Edegem | B-2650 | Belgium |
| Investigational Site Number : 0560004 | Ghent | 9000 | Belgium |
| Investigational Site Number :0560006 | Leuven | 3000 | Belgium |
| Investigational Site Number :0560008 | Liège | 4000 | Belgium |
| Investigational Site Number :0560002 | Mons | 7000 | Belgium |
| Investigational Site Number :0560001 | Overpelt | 3900 | Belgium |
| Investigational Site Number :1000002 | Pleven | 5800 | Bulgaria |
| Investigational Site Number :1000005 | Plovdiv | 4000 | Bulgaria |
| Investigational Site Number :1000004 | Sofia | 1113 | Bulgaria |
| Investigational Site Number :1000008 | Sofia | 1407 | Bulgaria |
| Investigational Site Number :1000001 | Sofia | 1431 | Bulgaria |
| Investigational Site Number :1000006 | Sofia | 1431 | Bulgaria |
| Investigational Site Number :1000009 | Sofia | 1680 | Bulgaria |
| Investigational Site Number :1240017 | Burnaby | British Columbia | V5G 2X6 | Canada |
| Investigational Site Number :1240011 | Halifax | Nova Scotia | B3H 1V7 | Canada |
| Investigational Site Number :1240003 | Ottawa | Ontario | K1H 8L6 | Canada |
| Investigational Site Number :1240008 | Toronto | Ontario | M4N 3M5 | Canada |
| Investigational Site Number :1240006 | Gatineau | Quebec | J8Y 1W2 | Canada |
| Investigational Site Number :1240005 | Greenfield Park | Quebec | J4V 2J2 | Canada |
| Investigational Site Number :1240004 | Montreal | Quebec | H2X 0A9 | Canada |
| Investigational Site Number :1240015 | Montreal | Quebec | H3A 2B4 | Canada |
| Investigational Site Number :1240007 | Sherbrooke | Quebec | J1H 5N4 | Canada |
| Investigational Site Number : 1240001 | Québec | G1J 1Z4 | Canada |
| Investigational Site Number :1240021 | Québec | G1W 4R4 | Canada |
| Investigational Site Number :1560006 | Beijing | 100034 | China |
| Investigational Site Number :1560012 | Beijing | 100053 | China |
| Investigational Site Number :1560021 | Beijing | 100700 | China |
| Investigational Site Number :1560003 | Beijing | 100730 | China |
| Investigational Site Number :1560009 | Beijing | 100730 | China |
| Investigational Site Number :1560004 | Changchun | 130021 | China |
| Investigational Site Number :1560015 | Changsha | 410008 | China |
| Investigational Site Number :1560005 | Chengdu | 610041 | China |
| Investigational Site Number :1560019 | Chongqing | 400016 | China |
| Investigational Site Number :1560035 | Fuzhou | 350005 | China |
| Investigational Site Number :1560001 | Guangzhou | 510630 | China |
| Investigational Site Number :1560007 | Hangzhou | 310009 | China |
| Investigational Site Number :1560014 | Shijiazhuang | 050000 | China |
| Investigational Site Number :1560008 | Taiyuan | 030001 | China |
| Investigational Site Number :1560017 | Xi'an | 710038 | China |
| Investigational Site Number :2030002 | Brno | 65691 | Czechia |
| Investigational Site Number :2030004 | Hradec Králové | 50005 | Czechia |
| Investigational Site Number :2030001 | Jihlava | 58633 | Czechia |
| Investigational Site Number :2030010 | Ostrava - Poruba | 70852 | Czechia |
| Investigational Site Number :2030005 | Prague | 12808 | Czechia |
| Investigational Site Number :2030003 | Teplice | 415 29 | Czechia |
| Investigational Site Number :2080001 | Esbjerg | 6700 | Denmark |
| Investigational Site Number :2080005 | Holstebro | 7500 | Denmark |
| Investigational Site Number :2080004 | Odense | 5000 | Denmark |
| Investigational Site Number :2460003 | Helsinki | 00180 | Finland |
| Investigational Site Number :2460001 | Tampere | 33520 | Finland |
| Investigational Site Number :2460002 | Turku | 20520 | Finland |
| Investigational Site Number :2500011 | Bron | 69500 | France |
| Investigational Site Number :2500005 | Clermont-Ferrand | 63003 | France |
| Investigational Site Number :2500015 | Gonesse | 95500 | France |
| Investigational Site Number :2500009 | Lille | 59037 | France |
| Investigational Site Number :2500006 | Montpellier | 34295 | France |
| Investigational Site Number :2500008 | Nancy | 54035 | France |
| Investigational Site Number :2500010 | Nantes | 44093 | France |
| Investigational Site Number :2500017 | Nîmes | 30029 | France |
| Investigational Site Number :2500016 | Paris | 75012 | France |
| Investigational Site Number :2500014 | Paris | 75013 | France |
| Investigational Site Number :2500007 | Paris | 75019 | France |
| Investigational Site Number :2500003 | Rennes | 35033 | France |
| Investigational Site Number :2500001 | Strasbourg | 67098 | France |
| Investigational Site Number :2500012 | Toulouse | 31059 | France |
| Investigational Site Number :2760005 | Bayreuth | 95445 | Germany |
| Investigational Site Number :2760009 | Berlin | 10117 | Germany |
| Investigational Site Number :2760001 | Dresden | 01307 | Germany |
| Investigational Site Number :2760012 | Essen | 45147 | Germany |
| Investigational Site Number :2760002 | Giessen | 35385 | Germany |
| Investigational Site Number :2760010 | Halle | 06120 | Germany |
| Investigational Site Number :2760006 | Hanover | 30625 | Germany |
| Investigational Site Number :2760008 | Münster | 48149 | Germany |
| Investigational Site Number :2760004 | Rostock | 18055 | Germany |
| Investigational Site Number :2760011 | Ulm | 89081 | Germany |
| Investigational Site Number :3000001 | Athens | 115 28 | Greece |
| Investigational Site Number :3000006 | Athens | 11535 | Greece |
| Investigational Site Number :3000002 | Athens | 12462 | Greece |
| Investigational Site Number :3000007 | Athens | 15125 | Greece |
| Investigational Site Number :3000004 | Larissa | 41110 | Greece |
| Investigational Site Number :3000003 | Thessaloniki | 546 36 | Greece |
| Investigational Site Number :3000005 | Thessaloniki | 57010 | Greece |
| Investigational Site Number :3480008 | Budapest | 1135 | Hungary |
| Investigational Site Number :3480004 | Budapest | 1145 | Hungary |
| Investigational Site Number :3480007 | Budapest | 1152 | Hungary |
| Investigational Site Number :3480002 | Pécs | 7623 | Hungary |
| Investigational Site Number :3480001 | Szeged | 6725 | Hungary |
| Investigational Site Number :3480006 | Tatabánya | 2800 | Hungary |
| Investigational Site Number :3560007 | Gurgaon | 122001 | India |
| Investigational Site Number :3560003 | Gurgaon | 122002 | India |
| Investigational Site Number :3560005 | India | India |
| Investigational Site Number :3560004 | Mangaluru | 575018 | India |
| Investigational Site Number : 3560009 | Nagpur | 440012 | India |
| Investigational Site Number :3560006 | New Delhi | 110029 | India |
| Investigational Site Number :3560002 | New Delhi | 110060 | India |
| Investigational Site Number :3760002 | Ashkelon | 78278 | Israel |
| Investigational Site Number :3760003 | Haifa | 31096 | Israel |
| Investigational Site Number :3760008 | Jerusalem | 91120 | Israel |
| Investigational Site Number :3760004 | Safed | 13100 | Israel |
| Investigational Site Number :3760001 | Tel Litwinsky | 52621 | Israel |
| Investigational Site Number :3800011 | Bergamo | 24127 | Italy |
| Investigational Site Number :3800007 | Cagliari | 09126 | Italy |
| Investigational Site Number :3800012 | Florence | 50134 | Italy |
| Investigational Site Number :3800016 | Florence | 50141 | Italy |
| Investigational Site Number :3800014 | Genova | 16132 | Italy |
| Investigational Site Number :3800013 | L’Aquila | 67010 | Italy |
| Investigational Site Number :3800004 | Milan | 20122 | Italy |
| Investigational Site Number :3800001 | Milan | 20132 | Italy |
| Investigational Site Number :3800010 | Milan | 20133 | Italy |
| Investigational Site Number :3800008 | Pavia | 27100 | Italy |
| Investigational Site Number :3800005 | Roma | 00152 | Italy |
| Investigational Site Number :3800009 | Roma | 00168 | Italy |
| Investigational Site Number :3920016 | Chiba | Chiba | 260-8677 | Japan |
| Investigational Site Number :3920022 | Morioka | Iwate | 020-8505 | Japan |
| Investigational Site Number :3920011 | Kyoto | Kyoto | 616-8255 | Japan |
| Investigational Site Number :3920020 | Sendai | Miyagi | 980-8574 | Japan |
| Investigational Site Number :3920005 | Niigata | Niigata | 951-8520 | Japan |
| Investigational Site Number :3920004 | Moriguchi-shi | Osaka | 570-8507 | Japan |
| Investigational Site Number :3920001 | Osaka | Osaka | 556-0016 | Japan |
| Investigational Site Number :3920018 | Kawagoe-shi | Saitama | 350-8550 | Japan |
| Investigational Site Number :3920003 | Kodaira-shi | Tokyo | 187-8551 | Japan |
| Investigational Site Number :3920010 | Ōta-ku | Tokyo | 146-0065 | Japan |
| Investigational Site Number :3920009 | Ube-shi | Yamaguchi | 755-8505 | Japan |
| Investigational Site Number :3920023 | Sagamihara-shi | 252-0392 | Japan |
| Investigational Site Number :4400003 | Kaunas | 50161 | Lithuania |
| Investigational Site Number :4400002 | Klaipėda | 92288 | Lithuania |
| Investigational Site Number :4400001 | Vilnius | 08661 | Lithuania |
| Investigational Site Number :5280001 | Amsterdam | 1081 GN | Netherlands |
| Investigational Site Number :5280003 | Breda | 4818 CK | Netherlands |
| Investigational Site Number :5280006 | Groningen | 9728 NZ | Netherlands |
| Investigational Site Number :5280002 | Sittard-Geleen | 6162 BG | Netherlands |
| Investigational Site Number :5780003 | Bergen | 5021 | Norway |
| Investigational Site Number :5780002 | Namsos | 7800 | Norway |
| Investigational Site Number :5780001 | Oslo | 0450 | Norway |
| Investigational Site Number :6160008 | Plewiska | Greater Poland Voivodeship | 62-064 | Poland |
| Investigational Site Number :6160003 | Bydgoszcz | Kuyavian-Pomeranian Voivodeship | 85-796 | Poland |
| Investigational Site Number :6160005 | Warsaw | Masovian Voivodeship | 01-211 | Poland |
| Investigational Site Number :6160006 | Warsaw | Masovian Voivodeship | 01-684 | Poland |
| Investigational Site Number :6160002 | Katowice | Silesian Voivodeship | 40-571 | Poland |
| Investigational Site Number :6160007 | Katowice | Silesian Voivodeship | 40-684 | Poland |
| Investigational Site Number :6160004 | Katowice | Silesian Voivodeship | 40-686 | Poland |
| Investigational Site Number :6160001 | Lodz | 90-549 | Poland |
| Investigational Site Number :6160012 | Lublin | 20-016 | Poland |
| Investigational Site Number :6160011 | Zabrze | 41-800 | Poland |
| Investigational Site Number :6200001 | Braga | 4710-243 | Portugal |
| Investigational Site Number :6200011 | Lisbon | 1162-050 | Portugal |
| Investigational Site Number :6200007 | Lisbon | 1349-019 | Portugal |
| Investigational Site Number :6200006 | Lisbon | 1649-035 | Portugal |
| Investigational Site Number :6200002 | Matosinhos Municipality | 4464-513 | Portugal |
| Investigational Site Number :6200010 | Porto | 4099-001 | Portugal |
| Investigational Site Number :6420008 | Bucharest | 022328 | Romania |
| Investigational Site Number :6420004 | Campulung Muscel | 115100 | Romania |
| Investigational Site Number :6420006 | Cluj-Napoca | 400012 | Romania |
| Investigational Site Number :6420003 | Constanța | 900123 | Romania |
| Investigational Site Number :6420013 | Oradea | 410154 | Romania |
| Investigational Site Number :6420005 | Sibiu | 550052 | Romania |
| Investigational Site Number :6420001 | Târgu Mureş | 540136 | Romania |
| Investigational Site Number :6420002 | Timișoara | 300736 | Romania |
| Investigational Site Number :6430018 | Barnaul | 656024 | Russia |
| Investigational Site Number :6430025 | Kaliningrad | 236035 | Russia |
| Investigational Site Number :6430003 | Kazan' | 420021 | Russia |
| Investigational Site Number :6430022 | Kemerovo | 650099 | Russia |
| Investigational Site Number :6430017 | Kirov | 610998 | Russia |
| Investigational Site Number :6430024 | Krasnoyarsk | 660029 | Russia |
| Investigational Site Number :6430020 | Moscow | 117997 | Russia |
| Investigational Site Number :6430002 | Moscow | 125367 | Russia |
| Investigational Site Number :6430013 | Moscow | 127015 | Russia |
| Investigational Site Number :6430001 | Moscow | 129110 | Russia |
| Investigational Site Number :6430008 | Moscow | 129128 | Russia |
| Investigational Site Number :6430021 | Nizhny Novgorod | 603137 | Russia |
| Investigational Site Number :6430006 | Nizhny Novgorod | 603155 | Russia |
| Investigational Site Number :6430005 | Novosibirsk | 630087 | Russia |
| Investigational Site Number :6430026 | Perm | 614990 | Russia |
| Investigational Site Number :6430007 | Pyatigorsk | 357538 | Russia |
| Investigational Site Number :6430016 | Rostov-on-Don | 344022 | Russia |
| Investigational Site Number :6430011 | Saint Petersburg | 197022 | Russia |
| Investigational Site Number :6430004 | Saint Petersburg | 197110 | Russia |
| Investigational Site Number :6430009 | Samara | 443095 | Russia |
| Investigational Site Number :6430019 | Saransk | 430032 | Russia |
| Investigational Site Number :6430014 | Smolensk | 214018 | Russia |
| Investigational Site Number :6430012 | Tyumen | 625000 | Russia |
| Investigational Site Number :6430010 | Ufa | 450005 | Russia |
| Investigational Site Number :6430023 | Yekaterinburg | 620102 | Russia |
| Investigational Site Number :7240007 | Seville | Andalusia | 41009 | Spain |
| Investigational Site Number :7240013 | Barcelona | Barcelona [Barcelona] | 08035 | Spain |
| Investigational Site Number :7240016 | Barcelona | Barcelona [Barcelona] | 08036 | Spain |
| Investigational Site Number :7240012 | Donostia / San Sebastian | Basque Country | 20014 | Spain |
| Investigational Site Number :7240014 | Salt | Girona [Gerona] | 17190 | Spain |
| Investigational Site Number :7240017 | Las Palmas de Gran Canaria | Las Palmas | 35010 | Spain |
| Investigational Site Number :7240004 | Majadahonda | Madrid | 28222 | Spain |
| Investigational Site Number :7240001 | Pozuelo de Alarcón | Madrid | 28223 | Spain |
| Investigational Site Number :7240008 | Córdoba | 14004 | Spain |
| Investigational Site Number :7240015 | Lleida | 25198 | Spain |
| Investigational Site Number :7240005 | Madrid | 28007 | Spain |
| Investigational Site Number :7240002 | Madrid | 28034 | Spain |
| Investigational Site Number :7240003 | Madrid | 28040 | Spain |
| Investigational Site Number :7240009 | Málaga | 29010 | Spain |
| Investigational Site Number :7240010 | Murcia | 30120 | Spain |
| Investigational Site Number :7240011 | Valencia | 46026 | Spain |
| Investigational Site Number :7920005 | Eskişehir | Turkey (Türkiye) |
| Investigational Site Number :7920010 | Hatay | Turkey (Türkiye) |
| Investigational Site Number :7920002 | Istanbul | 34098 | Turkey (Türkiye) |
| Investigational Site Number :7920009 | Istanbul | 34688 | Turkey (Türkiye) |
| Investigational Site Number :7920007 | Istanbul | 34785 | Turkey (Türkiye) |
| Investigational Site Number :7920006 | Istanbul | 34896 | Turkey (Türkiye) |
| Investigational Site Number :7920003 | Istanbul | Turkey (Türkiye) |
| Investigational Site Number :7920013 | Izmir | 35100 | Turkey (Türkiye) |
| Investigational Site Number :7920001 | İzmit | 41380 | Turkey (Türkiye) |
| Investigational Site Number :7920011 | Kütahya | 43100 | Turkey (Türkiye) |
| Investigational Site Number :7920012 | Mersin | 33070 | Turkey (Türkiye) |
| Investigational Site Number :7920008 | Trabzon | 61080 | Turkey (Türkiye) |
| Investigational Site Number :8040008 | Chernivtsi | 58000 | Ukraine |
| Investigational Site Number :8040016 | Chernivtsi | 58023 | Ukraine |
| Investigational Site Number :8040003 | Dnipro | 49005 | Ukraine |
| Investigational Site Number :8040010 | Ivano-Frankivsk | 76018 | Ukraine |
| Investigational Site Number :8040007 | Kharkiv | 61068 | Ukraine |
| Investigational Site Number :8040011 | Kharkiv | 61103 | Ukraine |
| Investigational Site Number :8040012 | Kharkiv | 61103 | Ukraine |
| Investigational Site Number :8040013 | Kyiv | 03115 | Ukraine |
| Investigational Site Number :8040005 | Lutsk | 43005 | Ukraine |
| Investigational Site Number :8040009 | Lviv | 79010 | Ukraine |
| Investigational Site Number :8040004 | Lviv | 79013 | Ukraine |
| Investigational Site Number :8040002 | Odesa | 65025 | Ukraine |
| Investigational Site Number :8040006 | Vinnytsia | 21050 | Ukraine |
| Investigational Site Number :8040014 | Zhytomyr | 10002 | Ukraine |
| Investigational Site Number :8260003 | Exeter | Devon | EX2 5DW | United Kingdom |
| Investigational Site Number :8260008 | Plymouth | Devon | PL6 8DH | United Kingdom |
| Investigational Site Number :8260010 | Swansea | Neath Port Talbot | SA6 6NL | United Kingdom |
| Investigational Site Number :8260012 | Nottingham | Nottinghamshire | NG7 2UH | United Kingdom |
| Investigational Site Number :8260013 | Oxford | Oxfordshire | OX3 9DZ | United Kingdom |
| Investigational Site Number :8260009 | Bristol | BS10 5NB | United Kingdom |
| Investigational Site Number :8260001 | Cardiff | CF4 4XY | United Kingdom |
| Investigational Site Number :8260005 | London | SW17 0RE | United Kingdom |
| Investigational Site Number :8260018 | London | W6 8RF | United Kingdom |
| Investigational Site Number :8260014 | Newcastle upon Tyne | NE1 4LP | United Kingdom |
| Investigational Site Number :8260019 | Salford | M6 8HD | United Kingdom |
| FG002 | OL: Placebo/Tolebrutinib 60 mg | Participants who received placebo in DB period and achieved 6-month CDP were given the option to receive OL tolebrutinib 60 mg tablet orally once daily up to approximately 39 months in the OL. |
| FG003 | OL: Tolebrutinib 60 mg/Tolebrutinib 60 mg | Participants who received tolebrutinib 60 mg in DB period and achieved 6-month CDP were given the option to continue to receive OL tolebrutinib 60 mg tablet orally once daily up to approximately 39 months in the OL. |
| COMPLETED | Completed DB period |
|
| NOT COMPLETED |
|
|
| OL |
|
|
Analysis was performed on randomized population.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | DB: Placebo | Participants received placebo matched to tolebrutinib orally once daily up to approximately 47 months. |
| BG001 | DB: Tolebrutinib 60 mg | Participants received tolebrutinib 60 mg tablet orally once daily up to approximately 47 months. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Time to Onset of 6-Month Confirmed Disability Progression (CDP) as Assessed by Expanded Disability Status Scale (EDSS) | The EDSS is a disability scale that assesses the following 7 functional domains: visual, brainstem, pyramidal [motor], cerebellar [coordination], sensory, cerebral, and bowel/bladder. The total EDSS ranges from 0 (normal) to 10 (death due to multiple sclerosis [MS]) (0.5 increments from 1-10; next increase after 0 is 1). Higher scores indicated increased disability. Time to onset of 6-month CDP was defined as the time from randomization to the onset of a sustained increase from baseline in EDSS score of >=1.0 point from the baseline EDSS score when the baseline score was <=5.0 or of >=0.5 points when the baseline EDSS score was >5.0 confirmed after a minimum 6-month interval. | The intent-to-treat (ITT) population included all randomized participants according to the intervention group allocated by the randomization, irrespective of the study intervention received. | Posted | Median | Full Range | months | Baseline (Day 1) up to approximately 47 months |
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| Secondary | Time to Onset of 3-month Confirmed Disability Progression as Assessed by Expanded Disability Status Scale | The EDSS is a disability scale that assesses the following 7 functional domains: visual, brainstem, pyramidal [motor], cerebellar [coordination], sensory, cerebral, and bowel/bladder. The total EDSS ranges from 0 (normal) to 10 (death due to MS) (0.5 increments from 1-10; next increase after 0 is 1). Higher scores indicated increased disability. Time to onset of 3-month CDP was defined as the time from randomization to the onset of a sustained increase from baseline in EDSS score (of >=1.0 point from the baseline EDSS score when the baseline score is <=5.0, of >=0.5 points when the baseline EDSS score is >5.0) confirmed after a minimum 3-month interval. The confirmation of 3-month CDP followed the same criteria as that of 6-month CDP. | The ITT population included all randomized participants according to the intervention group allocated by the randomization, irrespective of the study intervention received. | Posted | Median | Full Range | months | Baseline (Day 1) up to approximately 47 months |
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| Secondary | Mean Number of New and/or Enlarging T2-hyperintense Lesions Per Year | Magnetic resonance imaging (MRI) of the brain was performed to identify number of new and/or enlarging T2-hyperintense lesions defined as the sum of the individual number of new and/or enlarging T2 lesions from baseline up to and including the EOS visit. | The ITT population included all randomized participants according to the intervention group allocated by the randomization, irrespective of the study intervention received. | Posted | Mean | 95% Confidence Interval | number of T2 lesions | Baseline (Day 1) up to approximately 47 months |
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| Secondary | Time to Onset of Sustained 20% Increase in the 9-hole Peg Test (HPT) for at Least 3 Months | The 9-HPT is a brief, standardized, quantitative test of upper extremity function and the time to complete the 9-HPT is used to assess a participant's manual dexterity and fine motor skills. A participant was asked to place the pegs into the holes and remove them with the dominant and non-dominant hand; two successful trials for each hand. The amount of time (in seconds) required to place and remove all nine pegs was recorded for each trial (ranging from 10 to 300 seconds). The mean time to test completion served for assessment of the participant's hand dexterity. Higher value indicated worse outcome. An increase of >20% from the baseline in the 9-HPT was considered meaningful worsening; time to onset of sustained 20% increase for at least 3 months is presented. | The ITT population included all randomized participants according to the intervention group allocated by the randomization, irrespective of the study intervention received. | Posted | Median | Full Range | months | Baseline (Day 1) up to approximately 47 months |
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| Secondary | Time to Onset of Sustained 20% Increase in the Timed 25-foot Walk (T25-FW) for at Least 3 Months | The T25-FW test is a quantitative mobility and leg function performance test used to assess a participant's walking ability. A participant was directed to one end of a clearly marked 25-foot course and instructed to walk 25 feet as quickly as safely possible for 2 trials. The amount of time (in seconds) to walk 25 feet was recorded (ranging from 2.2 to 180 seconds). The mean walk time was used for assessment of the participant's walking ability. Higher value indicated worse outcome. An increase of >20% from the baseline in the T25-FW test was considered meaningful worsening; time to onset of sustained 20% increase for at least 3 months is presented. | The ITT population included all randomized participants according to the intervention group allocated by the randomization, irrespective of the study intervention received. | Posted | Median | Full Range | months | Baseline (Day 1) up to approximately 47 months |
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| Secondary | Time to Onset of 6-month Confirmed Disability Improvement (CDI) as Assessed by Expanded Disability Status Scale | The EDSS is a disability scale that assesses the following 7 functional domains: visual, brainstem, pyramidal [motor], cerebellar [coordination], sensory, cerebral, and bowel/bladder. The total EDSS ranges from 0 (normal) to 10 (death due to MS) (0.5 increments from 1-10; next increase after 0 is 1). Higher scores indicated increased disability. CDI was defined as a >=1 point decrease in the EDSS score from baseline confirmed over at least 6 months. | The ITT population included all randomized participants according to the intervention group allocated by the randomization, irrespective of the study intervention received. | Posted | Median | Full Range | months | Baseline (Day 1) up to approximately 47 months |
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| Secondary | Percent Change in Brain Volume at EOS Compared to Month 6 | MRI of the brain was performed to evaluate percent change in brain volume which is considered as a marker of the central nervous system degenerative process. Least squares (LS) mean is presented. | The ITT population included all randomized participants according to the intervention group allocated by the randomization, irrespective of the study intervention received. Only those participants with data collected at specified timepoints are reported. | Posted | Least Squares Mean | Standard Error | percent change | Month 6 to EOS (up to approximately 47 months) |
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| Secondary | Change From Baseline in Cognitive Function as Assessed by Symbol Digit Modalities Test (SDMT) at EOS | The SDMT is used to assess processing speed, divided attention, visual scanning, tracking and motor speed. It involves a simple substitution task using a reference key. The number of correct substitutions and number of items completed within a 90 second interval (maximum 110 seconds) are recorded. A decrease of 4 points from baseline on the SDMT is considered meaningful worsening. The score was the number of correctly coded items from 0-110 in 90 seconds; higher scores indicated better outcome. LS mean is presented. Baseline was defined as the last available value prior to the first dose of study intervention. | The ITT population included all randomized participants according to the intervention group allocated by the randomization, irrespective of the study intervention received. Only those participants with data collected at specified timepoints are reported. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline (Day 1) to EOS (up to approximately 47 months) |
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| Secondary | Change From Baseline in Cognitive Function as Assessed by California Verbal Learning Test Second Edition (CVLT-II) at EOS | The CVLT-II is a verbal learning and memory test consisting of recall and recognition of a list of 16 words. The list was read by the examiner, participants listened to the list and reported as many of the items as possible. For each assessment, 5 trials were completed. Standardized scores were used for analysis. The maximum possible score was 80 and a minimum was 0. A higher score indicated better recall meaning improved cognitive function. LS mean is presented. Baseline was defined as the last available value prior to the first dose of study intervention. | The ITT population included all randomized participants according to the intervention group allocated by the randomization, irrespective of the study intervention received. Only those participants with data collected at specified timepoints are reported. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline (Day 1) to EOS (up to approximately 47 months) |
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| Secondary | Change From Baseline in Multiple Sclerosis Quality of Life-54 (MSQoL-54) Questionnaire Score at EOS | MSQoL-54 is standardized instrument with generic and MS-specific items which generates 12 subscales & 2 single-item measures (satisfaction with sexual function [1 item] & change in health [1 item].12 subscales are as follows:a:physical health (10 items),b:health perceptions (5 items), c:energy (5 items),d:role limitation physical (4 items),e:sexual function (4 items),f:pain (3 items),g:social function (3 items),h:health distress (4 items),i:overall quality of life (2 items),j:emotional well-being (5 items),k:role limitations emotional (3 items) and l:cognitive function (4 items).Physical health composite score was calculated as weighted sum of 'a to h' subscales and mental health composite score was calculated as weighted sum of 'i to l' subscales mentioned above.Each composite score was transformed linearly to common 0 (worst) to 100 (best) score range;LS mean is presented.Higher score indicated improved QoL.Baseline:last available value prior to first dose of study intervention. | The ITT population included all randomized participants according to the intervention group allocated by the randomization, irrespective of the study intervention received. Only those participants with data collected at specified timepoints are reported. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline (Day 1) to EOS (up to approximately 47 months) |
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| Secondary | Number of Participants With Treatment-emergent Adverse Events (AEs), Treatment-emergent Serious AEs, Treatment-emergent AEs Leading to Permanent Study Intervention Discontinuation, and Treatment-emergent Adverse Events of Special Interest (AESIs) | An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. An AESI was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. TEAEs were defined as AEs that developed, worsened or became serious during the TE period. | The safety population included all randomized participants exposed to study intervention, regardless of the amount of exposure, analyzed according to the intervention actually received. | Posted | Count of Participants | Participants | From first dose of study intervention (Day 1) up to end of follow-up, up to approximately 47 months |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) of Tolebrutinib and M2 Metabolite | Blood samples were collected at specified timepoints to assess Cmax of tolebrutinib and M2 metabolite using a population pharmacokinetics (PopPK) model. | The PK population included all participants in the safety population with at least 1 non-missing PK sample after first dose of the study intervention. Only those participants with data collected at specified timepoints are reported. | Posted | Mean | Standard Deviation | nanogram/milliliter (ng/mL) | 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12 |
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| Secondary | Time to Maximum Observed Plasma Concentration (Tmax) of Tolebrutinib and M2 Metabolite | Blood samples were collected at specified timepoints to assess Tmax of tolebrutinib and M2 metabolite using a PopPK model. | The PK population included all participants in the safety population with at least 1 non-missing PK sample after first dose of the study intervention. Only those participants with data collected at specified timepoints are reported. | Posted | Mean | Standard Deviation | hour (h) | 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12 |
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| Secondary | Area Under the Plasma Concentration-time Curve Over the Last 24-hours Dosing Interval (AUC0-24) of Tolebrutinib and M2 Metabolite | Blood samples were collected at specified timepoints to assess AUC0-24 of tolebrutinib and M2 metabolite using a PopPK model. | The PK population included all participants in the safety population with at least 1 non-missing PK sample after first dose of the study intervention. Only those participants with data collected at specified timepoints are reported. | Posted | Mean | Standard Deviation | ng*h/mL | 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12 |
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| Secondary | Change From Baseline in Plasma Neurofilament Light Chain (NfL) and Serum Chitinase-3 Like Protein-1 (Chi3L1) Levels at EOS | Blood samples were collected at specified timepoints to assess change from baseline in NfL and Chi3L1. Baseline was defined as the last available value prior to the first dose of study intervention. | The safety population included all randomized participants exposed to study intervention, regardless of the amount of exposure, analyzed according to the intervention actually received. Only those participants with data collected at specified timepoints are reported. | Posted | Median | Inter-Quartile Range | picogram/mL | Baseline (Day 1) to EOS (up to approximately 47 months) |
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| Secondary | Change From Baseline in Cluster of Differentiation (CD)19+ B Cells at EOS | Blood samples were collected at specified timepoints to assess change from baseline in CD19+ B cells. Baseline was defined as the last available value prior to the first dose of study intervention. | The safety population included all randomized participants exposed to study intervention, regardless of the amount of exposure, analyzed according to the intervention actually received. Only those participants with data collected at specified timepoints are reported. | Posted | Median | Inter-Quartile Range | cells/microliter | Baseline (Day 1) to EOS (up to approximately 47 months) |
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| Secondary | Change From Baseline in Serum Immunoglobulin (Ig) Levels at EOS | Blood samples were collected at specified timepoints to assess change from baseline in IgG and IgM levels. Baseline was defined as the last available value prior to the first dose of study intervention. | The safety population included all randomized participants exposed to study intervention, regardless of the amount of exposure, analyzed according to the intervention actually received. Only those participants with data collected at specified timepoints are reported. | Posted | Median | Inter-Quartile Range | gram/liter | Baseline (Day 1) to EOS (up to approximately 47 months) |
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From first dose of study intervention (Day 1) up to end of follow-up, up to approximately 47 months
Analysis was performed on safety population. All-cause mortality was performed on randomized population. This was an event-driven (6-month CDP) trial with a variable treatment duration, EOS: up to approximately 47 months.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | DB: Placebo | Participants received placebo matched to tolebrutinib orally once daily up to approximately 47 months. | 1 | 377 | 39 | 375 | 182 | 375 |
| EG001 | DB: Tolebrutinib 60 mg | Participants received tolebrutinib 60 mg tablet orally once daily up to approximately 47 months. | 2 | 754 | 113 | 752 | 368 | 752 |
| EG002 | OL: Placebo/Tolebrutinib 60 mg | Participants who received placebo in DB period and achieved 6-month CDP were given the option to receive OL tolebrutinib 60 mg tablet orally once daily up to approximately 39 months in the OL. | 0 | 76 | 9 | 76 | 25 | 76 |
| EG003 | OL: Tolebrutinib 60 mg/Tolebrutinib 60 mg | Participants who received tolebrutinib 60 mg in DB period and achieved 6-month CDP were given the option to continue to receive OL tolebrutinib 60 mg tablet orally once daily up to approximately 39 months in the OL. | 0 | 120 | 11 | 120 | 41 | 120 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Appendicitis | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Bacterial Pyelonephritis | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Covid-19 | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Covid-19 Pneumonia | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Cystitis Bacterial | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Gastroenteritis Viral | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Herpes Zoster | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Pneumonia Bacterial | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Pneumonia Pneumococcal | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Pneumonia Viral | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Pyelonephritis Acute | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Pyelonephritis Chronic | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Respiratory Tract Infection | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Upper Respiratory Tract Infection | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Upper Respiratory Tract Infection Bacterial | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Varicella Zoster Pneumonia | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Viral Upper Respiratory Tract Infection | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Wound Infection | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Benign Neoplasm Of Thyroid Gland | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 27.0 | Systematic Assessment |
| |
| Bladder Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 27.0 | Systematic Assessment |
| |
| Bladder Cancer Stage 0, With Cancer In Situ | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 27.0 | Systematic Assessment |
| |
| Breast Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 27.0 | Systematic Assessment |
| |
| Chronic Myeloid Leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 27.0 | Systematic Assessment |
| |
| Endometrial Adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 27.0 | Systematic Assessment |
| |
| Lung Cancer Metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 27.0 | Systematic Assessment |
| |
| Prostate Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 27.0 | Systematic Assessment |
| |
| Renal Cell Carcinoma Stage I | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 27.0 | Systematic Assessment |
| |
| Squamous Cell Carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 27.0 | Systematic Assessment |
| |
| Uterine Leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 27.0 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDra 27.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDra 27.0 | Systematic Assessment |
| |
| Suicide Attempt | Psychiatric disorders | MedDra 27.0 | Systematic Assessment |
| |
| Brain Hypoxia | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Brain Oedema | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Generalised Tonic-Clonic Seizure | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Intracranial Hypotension | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Ischaemic Stroke | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Loss Of Consciousness | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Lumbar Radiculopathy | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Monoparesis | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Multiple Sclerosis | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Multiple Sclerosis Pseudo Relapse | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Multiple Sclerosis Relapse | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Muscle Spasticity | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Optic Neuritis | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Parkinsonian Gait | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Post-Traumatic Headache | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Restless Legs Syndrome | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Secondary Progressive Multiple Sclerosis | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Subarachnoid Haemorrhage | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Trigeminal Neuralgia | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Vertigo Cns Origin | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Retinal Detachment | Eye disorders | MedDra 27.0 | Systematic Assessment |
| |
| Uveitis | Eye disorders | MedDra 27.0 | Systematic Assessment |
| |
| Visual Field Defect | Eye disorders | MedDra 27.0 | Systematic Assessment |
| |
| Acute Vestibular Syndrome | Ear and labyrinth disorders | MedDra 27.0 | Systematic Assessment |
| |
| Vertigo Positional | Ear and labyrinth disorders | MedDra 27.0 | Systematic Assessment |
| |
| Acute Myocardial Infarction | Cardiac disorders | MedDra 27.0 | Systematic Assessment |
| |
| Atrial Fibrillation | Cardiac disorders | MedDra 27.0 | Systematic Assessment |
| |
| Left Ventricular Dysfunction | Cardiac disorders | MedDra 27.0 | Systematic Assessment |
| |
| Myocardial Infarction | Cardiac disorders | MedDra 27.0 | Systematic Assessment |
| |
| Sinus Node Dysfunction | Cardiac disorders | MedDra 27.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDra 27.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDra 27.0 | Systematic Assessment |
| |
| Pneumothorax Spontaneous | Respiratory, thoracic and mediastinal disorders | MedDra 27.0 | Systematic Assessment |
| |
| Abdominal Pain Lower | Gastrointestinal disorders | MedDra 27.0 | Systematic Assessment |
| |
| Duodenal Ulcer Haemorrhage | Gastrointestinal disorders | MedDra 27.0 | Systematic Assessment |
| |
| Faecaloma | Gastrointestinal disorders | MedDra 27.0 | Systematic Assessment |
| |
| Functional Gastrointestinal Disorder | Gastrointestinal disorders | MedDra 27.0 | Systematic Assessment |
| |
| Gastric Ulcer Haemorrhage | Gastrointestinal disorders | MedDra 27.0 | Systematic Assessment |
| |
| Haematemesis | Gastrointestinal disorders | MedDra 27.0 | Systematic Assessment |
| |
| Haemorrhoidal Haemorrhage | Gastrointestinal disorders | MedDra 27.0 | Systematic Assessment |
| |
| Megacolon | Gastrointestinal disorders | MedDra 27.0 | Systematic Assessment |
| |
| Obstructive Pancreatitis | Gastrointestinal disorders | MedDra 27.0 | Systematic Assessment |
| |
| Terminal Ileitis | Gastrointestinal disorders | MedDra 27.0 | Systematic Assessment |
| |
| Upper Gastrointestinal Haemorrhage | Gastrointestinal disorders | MedDra 27.0 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDra 27.0 | Systematic Assessment |
| |
| Cholecystitis Acute | Hepatobiliary disorders | MedDra 27.0 | Systematic Assessment |
| |
| Drug-Induced Liver Injury | Hepatobiliary disorders | MedDra 27.0 | Systematic Assessment |
| |
| Gallbladder Polyp | Hepatobiliary disorders | MedDra 27.0 | Systematic Assessment |
| |
| Hepatic Failure | Hepatobiliary disorders | MedDra 27.0 | Systematic Assessment |
| |
| Chondropathy | Musculoskeletal and connective tissue disorders | MedDra 27.0 | Systematic Assessment |
| |
| Muscular Weakness | Musculoskeletal and connective tissue disorders | MedDra 27.0 | Systematic Assessment |
| |
| Neck Pain | Musculoskeletal and connective tissue disorders | MedDra 27.0 | Systematic Assessment |
| |
| Pain In Extremity | Musculoskeletal and connective tissue disorders | MedDra 27.0 | Systematic Assessment |
| |
| Acute Kidney Injury | Renal and urinary disorders | MedDra 27.0 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDra 27.0 | Systematic Assessment |
| |
| Renal Colic | Renal and urinary disorders | MedDra 27.0 | Systematic Assessment |
| |
| Acquired Hydrocele | Reproductive system and breast disorders | MedDra 27.0 | Systematic Assessment |
| |
| Benign Prostatic Hyperplasia | Reproductive system and breast disorders | MedDra 27.0 | Systematic Assessment |
| |
| Cervical Dysplasia | Reproductive system and breast disorders | MedDra 27.0 | Systematic Assessment |
| |
| Gait Disturbance | General disorders | MedDra 27.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDra 27.0 | Systematic Assessment |
| |
| Oedema Peripheral | General disorders | MedDra 27.0 | Systematic Assessment |
| |
| Rebound Effect | General disorders | MedDra 27.0 | Systematic Assessment |
| |
| Alanine Aminotransferase Increased | Investigations | MedDra 27.0 | Systematic Assessment |
| |
| Cardiac Murmur | Investigations | MedDra 27.0 | Systematic Assessment |
| |
| Ankle Fracture | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Brain Contusion | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Cervical Vertebral Fracture | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Craniocerebral Injury | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Extradural Haematoma | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Femoral Neck Fracture | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Femur Fracture | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Fibula Fracture | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Hip Fracture | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Humerus Fracture | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Intentional Overdose | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Joint Dislocation | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Limb Injury | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Lumbar Vertebral Fracture | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Pelvic Fracture | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Post-Traumatic Pain | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Radius Fracture | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Rib Fracture | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Road Traffic Accident | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Shoulder Fracture | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Skin Laceration | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Skull Fractured Base | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Spinal Compression Fracture | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Subcutaneous Haematoma | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Tibia Fracture | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Traumatic Haemothorax | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Traumatic Liver Injury | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Ulna Fracture | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Assisted Suicide | Surgical and medical procedures | MedDra 27.0 | Systematic Assessment |
| |
| Rehabilitation Therapy | Surgical and medical procedures | MedDra 27.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Covid-19 | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDra 27.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDra 27.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDra 27.0 | Systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | MedDra 27.0 | Systematic Assessment |
| |
| Accidental Overdose | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDra 27.0 | Systematic Assessment |
|
The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Transparency Team | Sanofi aventis recherche & développement | 800-633-1610 | #6 | Contact-US@sanofi.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 30, 2024 | Jun 3, 2025 | SAP_001.pdf |
| Progressive disease |
|
| Poor compliance to protocol |
|
| Adverse Event |
|
| Other |
|
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures are reported and continued when previous outcome measure was statistically significant at 2-sided 0.05. Primary and first 6 secondary endpoints are included in this procedure. |
| Units | Counts |
|---|---|
| Participants |
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| Units | Counts |
|---|---|
| Participants |
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| Units | Counts |
|---|---|
| Participants |
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| Units | Counts |
|---|---|
| Participants |
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| OG001 |
| DB: Tolebrutinib 60 mg |
Participants received tolebrutinib 60 mg tablet orally once daily up to approximately 47 months. |
|
|
Participants received tolebrutinib 60 mg tablet orally once daily up to approximately 47 months. |
| OG002 | OL: Placebo/Tolebrutinib 60 mg | Participants who received placebo in DB period and achieved 6-month CDP were given the option to receive OL tolebrutinib 60 mg tablet orally once daily up to approximately 39 months in the OL. |
| OG003 | OL: Tolebrutinib 60 mg/Tolebrutinib 60 mg | Participants who received tolebrutinib 60 mg in DB period and achieved 6-month CDP were given the option to continue to receive OL tolebrutinib 60 mg tablet orally once daily up to approximately 39 months in the OL. |
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