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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04410978
Other study ID # EFC16033
Secondary ID U1111-1238-14182
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date June 30, 2020
Est. completion date August 15, 2024

Study information

Verified date April 2024
Source Sanofi
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Primary Objective: To assess efficacy of daily SAR442168 compared to a daily dose of 14 mg teriflunomide (Aubagio) measured by annualized adjudicated relapse rate (ARR) in participants with relapsing forms of MS Secondary Objective: To assess efficacy of SAR442168 compared to teriflunomide (Aubagio) on disability progression, MRI lesions, cognitive performance and quality of life To evaluate the safety and tolerability of daily SAR442168 To evaluate population pharmacokinetics (PK) of SAR442168 and relevant metabolites and its relationship to efficacy and safety To evaluate pharmacodynamics (PD) of SAR442168


Description:

Study duration will vary per participant in this event driven trial with a treatment duration of approximately 18 to 36 months. Participants completing the study will be offered to participate in a long term safety study.


Other known NCT identifiers
  • NCT04964791

Recruitment information / eligibility

Status Active, not recruiting
Enrollment 900
Est. completion date August 15, 2024
Est. primary completion date August 15, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 55 Years
Eligibility Inclusion criteria : - The participant must be 18 to 55 years of age, inclusive, at the time of signing the informed consent - The participant must have been diagnosed with RMS according to the 2017 revision of the McDonald diagnostic criteria - The participant has an expanded disability status scale (EDSS) score =5.5 at the first Screening Visit - The participant must have at least 1 of the following prior to screening: - =1 documented relapse within the previous year OR - =2 documented relapses within the previous 2 years, OR - =1 documented Gd enhancing lesion on an MRI scan within the previous year - Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies - Male participants are eligible to participate if they agree to the following during the intervention period and until accelerated elimination procedure: - Refrain from donating sperm Plus either: - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR - Must agree to use contraception/barrier as detailed below: Agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant - A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions apply: - Is not a WOCBP OR - Is a WOCBP and agrees to use a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, during the intervention period and until accelerated elimination procedure is completed (or for at least 10 days after the last dose of SAR442168, if the case was unblinded) - A WOCBP must have a negative highly sensitive pregnancy test at screening and within 24hours before the first dose of study intervention. - If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. - The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. - The participant must have given written informed consent prior to undertaking any study related procedure. This includes consent to comply with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. In countries where the legal age of maturity is greater than 18 years, a specific ICF for such legally minor participants must also be signed by the participant's legally authorized representative Exclusion criteria: - The participant has been diagnosed with primary progressive multiple sclerosis (PPMS) according to the 2017 revision of the McDonald diagnostic criteria or with nonrelapsing secondary progressive multiple sclerosis (SPMS) - The participant has a history of infection or may be at risk for infection including but not limited to: HIV, transplantation, live attenuated vaccines, progressive multifocal leukoencephalopathy, tuberculosis, hepatitis B or C, any persistent chronic or active recurring infection - Clinically significant laboratory abnormalities (including evidence of liver injury) or electrocardiogram abnormalities at Screening. - The participant has conditions or situations that would adversely affect participation in this study, including but not limited to: - A short life expectancy due to pre-existing health condition(s) as determined by their treating neurologist - Medical condition(s) or concomitant disease(s) making them nonevaluable for the primary efficacy endpoint or that would adversely affect participation in this study, as judged by the Investigator - A requirement for concomitant treatment that could bias the primary evaluation - The participant has a history of or currently has concomitant medical or clinical conditions that would adversely affect participation in this study - At screening, the participant is positive for hepatitis B surface antigen and/or hepatitis B core antibody and/or is positive for hepatitis C antibody - The participant has any of the following: - A bleeding disorder or known platelet dysfunction at any time prior to the screening visit - A platelet count <150 000/µL at the screening visit - The participant has a lymphocyte count below the lower limit of normal (LLN) at the screening visit - The presence of psychiatric disturbance or substance abuse - Prior/concomitant therapy - The participant is receiving potent and moderate inducers of cytochrome P450 (CYP) 3A or potent inhibitors of CYP2C8 hepatic enzymes - The participant is receiving anticoagulant/antiplatelet therapies The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Design


Intervention

Drug:
Tolebrutinib
Pharmaceutical form: Tablet Route of administration: Oral
Teriflunomide HMR1726
Pharmaceutical form: Tablet Route of administration: Oral
Placebo to match Tolebrutinib
Pharmaceutical form: Tablet Route of administration: Oral
Placebo to match Teriflunomide
Pharmaceutical form: Tablet Route of administration: Oral

Locations

Country Name City State
Austria Investigational Site Number :0400004 Linz
Belarus Investigational Site Number :1120004 Vitebsk
Belarus Investigational Site Number :1120005 Vitebsk
Bulgaria Investigational Site Number :1000002 Pleven
Bulgaria Investigational Site Number :1000005 Plovdiv
Bulgaria Investigational Site Number :1000001 Sofia
Bulgaria Investigational Site Number :1000004 Sofia
Bulgaria Investigational Site Number :1000006 Sofia
Bulgaria Investigational Site Number :1000008 Sofia
Bulgaria Investigational Site Number :1000009 Sofia
Canada Investigational Site Number :1240006 Gatineau Quebec
Canada Investigational Site Number :1240003 Ottawa Ontario
Canada Investigational Site Number :1240013 Toronto Ontario
Canada Investigational Site Number :1240016 Vancouver British Columbia
China Investigational Site Number :1560022 Baotou
China Investigational Site Number :1560001 Beijing
China Investigational Site Number :1560006 Beijing
China Investigational Site Number :1560009 Beijing
China Investigational Site Number :1560010 Beijing
China Investigational Site Number :1560012 Beijing
China Investigational Site Number :1560021 Beijing
China Investigational Site Number :1560023 Beijing
China Investigational Site Number :1560025 Beijing
China Investigational Site Number :1560004 Changchun
China Investigational Site Number :1560015 Changsha
China Investigational Site Number :1560005 Chengdu
China Investigational Site Number :1560019 Chongqing
China Investigational Site Number :1560035 Fuzhou
China Investigational Site Number :1560002 Guangzhou
China Investigational Site Number :1560016 Guangzhou
China Investigational Site Number :1560028 Guangzhou
China Investigational Site Number :1560027 Hohhot
China Investigational Site Number :1560042 Nanjing
China Investigational Site Number :1560044 Nanjing
China Investigational Site Number :1560003 Shanghai
China Investigational Site Number :1560018 Shenyang
China Investigational Site Number :1560014 Shijiazhuang
China Investigational Site Number :1560008 Taiyuan
China Investigational Site Number :1560020 Tianjin
China Investigational Site Number :1560011 Wuhan
China Investigational Site Number :1560017 Xi'an
China Investigational Site Number :1560033 Yinchuan
Czechia Investigational Site Number :2030004 Hradec Kralove
Czechia Investigational Site Number :2030009 Pardubice
Czechia Investigational Site Number :2030003 Teplice
Czechia Investigational Site Number :2030007 Zlin
Denmark Investigational Site Number :2080001 Esbjerg
Denmark Investigational Site Number :2080005 Holstebro
Estonia Investigational Site Number :2330001 Tallinn
Estonia Investigational Site Number :2330002 Tartu
Finland Investigational Site Number :2460003 Helsinki
Finland Investigational Site Number :2460001 Tampere
Finland Investigational Site Number :2460002 Turku
Germany Investigational Site Number :2760001 Dresden
Germany Investigational Site Number :2760019 Düsseldorf
Germany Investigational Site Number :2760016 Hamburg
Germany Investigational Site Number :2760008 Münster
Germany Investigational Site Number :2760004 Rostock
Germany Investigational Site Number :2760011 Ulm
Hong Kong Investigational Site Number : 3440001 Shatin, NT
Italy Investigational Site Number :3800011 Bergamo
Italy Investigational Site Number :3800015 Catania
Italy Investigational Site Number :3800012 Firenze
Italy Investigational Site Number :3800014 Genova
Italy Investigational Site Number :3800001 Milano
Italy Investigational Site Number :3800010 Milano
Italy Investigational Site Number :3800003 Napoli
Italy Investigational Site Number :3800006 Napoli
Italy Investigational Site Number :3800007 Orbassano Torino
Italy Investigational Site Number :3800008 Pavia
Italy Investigational Site Number :3800002 Pozzilli Isernia
Italy Investigational Site Number :3800005 Roma
Italy Investigational Site Number :3800009 Roma
Italy Investigational Site Number :3800013 Roma
Japan Investigational Site Number :3920014 Bunkyo-ku Tokyo
Japan Investigational Site Number :3920016 Chiba-shi Chiba
Japan Investigational Site Number :3920018 Kawagoe-shi Saitama
Japan Investigational Site Number :3920003 Kodaira-shi Tokyo
Japan Investigational Site Number :3920008 Koriyama-shi Fukushima
Japan Investigational Site Number :3920004 Moriguchi-shi Osaka
Japan Investigational Site Number :3920022 Morioka-shi Iwate
Japan Investigational Site Number :3920005 Niigata-shi Niigata
Japan Investigational Site Number :3920001 Osaka-shi Osaka
Japan Investigational Site Number :3920010 Ota-ku Tokyo
Japan Investigational Site Number :3920023 Sagamihara-shi
Japan Investigational Site Number :3920013 Shinjuku-ku Tokyo
Japan Investigational Site Number :3920012 Tsukuba-shi Ibaraki
Japan Investigational Site Number :3920009 Ube-shi Yamaguchi
Lithuania Investigational Site Number :4400003 Kaunas
Lithuania Investigational Site Number :4400002 Klaipeda
Lithuania Investigational Site Number :4400004 Siauliai
Lithuania Investigational Site Number :4400001 Vilnius
Mexico Investigational Site Number :4840001 Mexico
Mexico Investigational Site Number :4840002 Mexico
Mexico Investigational Site Number :4840003 Veracruz
Poland Investigational Site Number :6160003 Bydgoszcz Kujawsko-pomorskie
Poland Investigational Site Number :6160009 Glogow Mlp. Podkarpackie
Poland Investigational Site Number :6160002 Katowice Slaskie
Poland Investigational Site Number :6160004 Katowice Slaskie
Poland Investigational Site Number :6160001 Lodz
Poland Investigational Site Number :6160008 Plewiska Wielkopolskie
Poland Investigational Site Number :6160005 Warszawa Mazowieckie
Poland Investigational Site Number :6160006 Warszawa Mazowieckie
Romania Investigational Site Number :6420015 Brasov
Romania Investigational Site Number :6420008 Bucuresti
Romania Investigational Site Number :6420004 Campulung
Romania Investigational Site Number :6420003 Constanta
Romania Investigational Site Number :6420010 Oradea
Romania Investigational Site Number :6420005 Sibiu
Romania Investigational Site Number :6420001 Targu Mures
Romania Investigational Site Number :6420002 Timisoara
Russian Federation Investigational Site Number :6430014 Krasnoyarsk
Russian Federation Investigational Site Number :6430002 Moscow
Russian Federation Investigational Site Number :6430008 Moscow
Russian Federation Investigational Site Number :6430003 Nizhny Novgorod
Russian Federation Investigational Site Number :6430011 Nizhny Novgorod
Russian Federation Investigational Site Number :6430007 Pyatigorsk
Russian Federation Investigational Site Number :6430012 Rostov-on-Don
Russian Federation Investigational Site Number :6430005 Samara
Russian Federation Investigational Site Number :6430009 Smolensk
Russian Federation Investigational Site Number :6430001 St-Petersburg
Russian Federation Investigational Site Number :6430006 Tyumen
Russian Federation Investigational Site Number :6430004 Ufa
Spain Investigational Site Number :7240009 Barcelona Barcelona [Barcelona]
Spain Investigational Site Number :7240004 Córdoba
Spain Investigational Site Number :7240008 Donostia Pais Vasco
Spain Investigational Site Number :7240005 Málaga
Spain Investigational Site Number :7240006 Murcia
Spain Investigational Site Number :7240001 Pozuelo De Alarcón Madrid
Spain Investigational Site Number :7240003 Sevilla Andalucia
Spain Investigational Site Number :7240007 Valencia
Sweden Investigational Site Number :7520001 Göteborg
Sweden Investigational Site Number :7520002 Stockholm
Taiwan Investigational Site Number :1580007 Hsinchu City
Taiwan Investigational Site Number :1580005 Kaohsiung
Taiwan Investigational Site Number :1580003 Taichung
Taiwan Investigational Site Number :1580002 Taipei
Taiwan Investigational Site Number :1580006 Taoyuang
Turkey Investigational Site Number :7920005 Eskisehir
Turkey Investigational Site Number :7920011 Hatay
Turkey Investigational Site Number :7920002 Istanbul
Turkey Investigational Site Number :7920003 Istanbul
Turkey Investigational Site Number :7920007 Istanbul
Turkey Investigational Site Number :7920009 Istanbul
Turkey Investigational Site Number :7920008 Izmir
Turkey Investigational Site Number :7920010 Izmir
Turkey Investigational Site Number :7920001 Kocaeli
Turkey Investigational Site Number :7920006 Mersin
Ukraine Investigational Site Number :8040011 Ivano-Frankivsk
Ukraine Investigational Site Number :8040013 Kharkiv
Ukraine Investigational Site Number :8040016 Kharkiv
Ukraine Investigational Site Number :8040008 Kherson
Ukraine Investigational Site Number :8040014 Kyiv
Ukraine Investigational Site Number :8040010 Lutsk
Ukraine Investigational Site Number :8040001 Lviv
Ukraine Investigational Site Number :8040009 Odesa
United States University of Colorado-Site Number:8400012 Aurora Colorado
United States University of Alabama MS Center-Site Number:8400013 Birmingham Alabama
United States Tufts Medical Center-Site Number:8400072 Boston Massachusetts
United States Optimed Research, LTD-Site Number:8400147 Columbus Ohio
United States The Ohio State University Wexner Medical Center-Site Number:8400150 Columbus Ohio
United States University of Texas Southwestern Medical Center-Site Number:8400077 Dallas Texas
United States Michigan Institute For Neurological Disorders-Site Number:8400058 Farmington Hills Michigan
United States Beth Israel Deaconess Medical Center-Site Number:8400064 Fort Myers Florida
United States Consultants In Neurology-Site Number:8400011 Northbrook Illinois
United States Oklahoma Medical Research Foundation-Site Number:8400018 Oklahoma City Oklahoma
United States The Memorial Hospital-Site Number:8400033 Owosso Michigan
United States Sharlin Health & Neurology-Site Number:8400093 Ozark Missouri
United States Providence Multiple Sclerosis Center-Site Number:8400020 Portland Oregon
United States Meridian Clinical Research, LLC-Site Number:8400005 Raleigh North Carolina
United States Missouri Baptist Medical Center-Site Number:8400019 Saint Louis Missouri
United States University of San Francisco, Sandler Neurosciences Center-Site Number:8400137 San Francisco California
United States Meridian Clinical Research-Site Number:8400003 Savannah Georgia
United States Multiple Sclerosis Center, Swedish Neuroscience Institute-Site Number:8400121 Seattle Washington
United States Axiom Clinical Research of Florida-Site Number:8400001 Tampa Florida
United States University of South Florida-Site Number:8400006 Tampa Florida
United States Georgetown University Medical Center-Site Number:8400119 Washington District of Columbia
United States Columbus Neuroscience-Site Number:8400010 Westerville Ohio
United States Wake Forest University Baptist Medical Center-Site Number:8400116 Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Austria,  Belarus,  Bulgaria,  Canada,  China,  Czechia,  Denmark,  Estonia,  Finland,  Germany,  Hong Kong,  Italy,  Japan,  Lithuania,  Mexico,  Poland,  Romania,  Russian Federation,  Spain,  Sweden,  Taiwan,  Turkey,  Ukraine, 

Outcome

Type Measure Description Time frame Safety issue
Primary Annualized Adjudicated Relapse Rate : Number of confirmed adjudicated protocol defined relapses Annualized Adjudicated Relapse Rate : Number of confirmed adjudicated protocol defined relapses Up to approximately 36 months
Secondary Time to onset of confirmed disability worsening confirmed over at least 6 months Time to onset of confirmed disability worsening (CDW), confirmed over at least 6 months, defined as follows:
increase of =1.5 points from the baseline expanded disability status scale (EDSS) score when the baseline score is 0 OR
increase of =1.0 point from the baseline EDSS score when the baseline score is 0.5 to =5.5 OR
increase of =0.5 point from the baseline EDSS score when the baseline score is >5.5 - 5.
Up to approximately 36 months
Secondary Time to onset of CDW, assessed by the EDSS score and confirmed over at least 3 months Up to approximately 36 months
Secondary Total number of new and/or enlarging T2 hyperintense lesions as detected by MRI from Month 6 through the end of study (EOS) From 6 months up to approximately 36 months
Secondary Total of Gd-enhancing T1 hyperintense lesions as detected by MRI from 6 months through the EOS From 6 months up to approximately 36 months
Secondary Change in cognitive function Change in cognitive function from baseline to the end of study (EOS) as assessed by SDMT and by CVLT-II where available From Baseline up to approximately 36 months
Secondary Time to confirmed disability improvement Time to confirmed disability improvement (CDI), defined as a =1.0 point decrease on the EDSS from the baseline EDSS score confirmed over at least 6 months From Baseline up to approximately 36 months
Secondary Percent Change in Brain volume loss (BVL) Brain volume loss (BVL) rate as detected by brain MRI from Month 6 to the EOS From 6 months up to approximately 36 months
Secondary Change in Multiple Sclerosis Quality of Life Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) from the baseline through the EOS From Baseline up to approximately 36 months
Secondary Number of participants with adverse events A(Es) leading to permanent study intervention discontinuation, and adverse events of special interest (AESI) From screening until end of study approximately 36 months
Secondary Population Pharmacokinetics - Concentration SAR442168 and relevant metabolites at 6 months Plasma concentration of SAR442168 (population PK assessment) at 6 Months 6 Months
Secondary Population Pharmacokinetics Concentration of SAR442168 and relevant metabolites at 9 Months Plasma concentration of SAR442168 (population PK assessment) at 9 Months 9 Months
Secondary Population Pharmacokinetics - Concentration of SAR442168 and relevant metabolites at 12 Months Plasma concentration of SAR442168 (population PK assessment) at 12 Months 12 Months
Secondary Change in plasma NfL Change in plasma neurofilament light chain (NfL) levels at the EOS compared to baseline From Baseline until end of study approximately 36 months
Secondary Change in lymphocyte Phenotype Change in lymphocyte phenotype subsets in whole blood at the EOS compared to baseline in a subset of participants From Baseline until end of study approximately 36 months
Secondary Changes in plasma Immunoglobulin levels Changes in serum immunoglobulin level at the EOS compared to baseline From Baseline until end of study (up to 36 months)
Secondary Change in CHI3L1 levels Change in serum Chi3L1 levels at the EOS compared to baseline From Baseline until end of study approximately 36 months
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