A Phase 2b dose-finding study for SAR442168, a Bruton's tyrosine kinase inhibitor, in participants with relapsing multiple sclerosis

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 5

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 must have at least 1 documented relapse within the previous year, *2 documented relapses within the previous 2 years, or *1 active Gd-enhancing brain lesion on an MRI scan in the past 6 months and prior to screening.
- A female participant must use a double contraception method including a highly effective method of birth control, except if she has undergone sterilization at least 3 months earlier or is postmenopausal. Menopause is defined as being amenorrheic for *2 years with serum
follicle-stimulating hormone (FSH) level >30 UI/L.
- Male participants, whose partners are of childbearing potential (including breastfeeding women), must accept to use, during sexual intercourse, a double contraceptive method according to the following algorithm: (condom) plus (intrauterine device or hormonal contraceptive) from inclusion up to 3 months after the last dose.
- Male participants whose partners are pregnant must use, during sexual intercourse, a condom from inclusion up to 3 months after the last dose.
- Male participants must have agreed not to donate sperm from the inclusion up to 3 months after the last dose.

Exclusion Criteria

- The participant has been diagnosed with PPMS according to the 2017 revision of the McDonald diagnostic criteria or with non-relapsing SPMS.
- 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; Contraindication for MRI, ie, presence of pacemaker, metallic implants in high-risk areas (ie, artificial heart valves, aneurysm/vessel clips), presence of metallic material
(eg, shrapnel) in high risk areas, known history of allergy to any contrast medium, or history of claustrophobia that would prevent completion of all protocol-scheduled MRI; Contraindications to use MRI Gd contrast-enhancing preparations.
- The participant has a history of or currently has concomitant medical or clinical conditions that would adversely affect participation in this study, including but not limited to: A history of T-lymphocyte or T-lymphocyte-receptor vaccination, transplantation and/or antirejection therapy; A history of diagnosis of progressive multifocal leukoencephalopathy (PML) or evidence of findings suggestive of PML on the baseline MRI; A history of infection with the human immunodeficiency virus; A history of active or latent tuberculosis; Any other active infections that would adversely affect participation or IMP administration in this study, as judged by the Investigator; A history of malignancy within 10 years prior to the first screening visit, except effectively treated carcinoma in situ of the cervix or adequately treated non-metastatic squamous or basal cell carcinoma of the skin; A history of alcohol or drug abuse within 1 year prior to the first screening visit; A history of any psychiatric disease, behavioral condition, or depression requiring hospitalization within 2 years prior to the first screening visit; Presence of any screening laboratory or ECG values outside normal limits that are considered in the Investigator*s judgment to be clinically significant; Presence of liver injury defined as underlying hepatobiliary disease or screening alanine aminotransferase (ALT) >3 x upper limit of normal (ULN).
- 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 first screening visit; A platelet count <150 000/*L at the screening visit.
- The participant has a lymphocyte count less than the lower limit of normal (LLN) at the screening visit.
- The participant has received any live (attenuated) vaccine within 2 months before the first treatment visit.
- The participant has received any of the following medications/treatments within the specified time frame before any baseline assessment (no wash-out is required forinterferons beta or glatiramer acetate treatments):
-Systemic corticosteroids, adrenocorticotropic hormone 1 month prior to screening MRI scan
-Dimethyl fumarate 1 month prior to randomization
-Intravenous (IV) immun

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Number of new Gd-enhancing T1-hyperintense lesions at the end of 12 weeks of<br /><br>SAR442168 treatment as detected by brain MRI.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Number of new or enlarging T2 lesions at the end of 12 weeks of SAR442168<br /><br>treatment<br /><br>- Number of Gd-enhancing T1-hyperintense lesions at the end of 12 weeks of<br /><br>SAR442168 treatment<br /><br>- Adverse events (AEs), serious adverse events (SAEs), potentially clinically<br /><br>significant abnormalities in laboratory tests, electrocardiogram (ECG), or<br /><br>vital signs during the study period</p><br>