Resumen

Objetivo primario: Evaluar la eficacia de SAR442168 diario en comparación con una dosis diaria de 14 mg de teriflunomida (Aubagio) medida por la tasa anualizada de recaídas adjudicadas (TAR) en participantes con formas recurrentes de EM. Objetivo secundario: Evaluar la eficacia de SAR442168 en comparación con teriflunomida (Aubagio) sobre la progresión de la discapacidad, las lesiones en RM, el rendimiento cognitivo y la calidad de vida. Evaluar la seguridad y tolerabilidad de SAR442168 diario. Evaluar la farmacodinamia (FD) de SAR442168.

Descripción detallada

La duración del estudio varió por participante en este ensayo impulsado por eventos, con una duración del tratamiento de aproximadamente 18 a 36 meses. A los participantes que completaron el estudio se les ofreció participar en un estudio de seguridad a largo plazo.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 55 YearsSexo: ALL

Criterios de inclusión

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) and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during the study and for the same period of time.
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

Criterios de exclusión

The participant has been diagnosed with primary progressive multiplesclerosis (PPMS) according to the 2017 revision of the McDonald diagnostic criteria or with nonrelapsing secondary progressive multiplesclerosis (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

Intervenciones

drug

Tolebrutinib

Pharmaceutical form: Tablet Route of administration: Oral

drug

Teriflunomide HMR1726

Pharmaceutical form: Tablet Route of administration: Oral

drug

Placebo to match Tolebrutinib

Pharmaceutical form: Tablet Route of administration: Oral

drug

Placebo to match Teriflunomide

Pharmaceutical form: Tablet Route of administration: Oral

Ubicaciones

Investigational Site Number :0320004

CABA, Buenos Aires, Argentina

Investigational Site Number :0320002

Capital Federal, Buenos Aires, Argentina

Investigational Site Number :0320001

CABA, Buenos Aires F.D., Argentina

Investigational Site Number :0320003

Rosario, Santa Fe Province, Argentina

Investigational Site Number :0320005

San Miguel de Tucumán, Argentina

Estudio de fase 3, aleatorizado, doble ciego, de eficacia y seguridad que compara SAR442168 con teriflunomida (Aubagio®) en participantes con formas recurrentes de esclerosis múltiple

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Tolebrutinib

Teriflunomide HMR1726

Placebo to match Tolebrutinib

Placebo to match Teriflunomide

Ubicaciones

Investigational Site Number :0320004

Investigational Site Number :0320002

Investigational Site Number :0320001

Investigational Site Number :0320003

Investigational Site Number :0320005

Patrocinadores