Clinical Trials

Inclusion Criteria:

• Participant must be 18 to 60 years of age at the time of signing the informed consent.
• The participant must have a previous diagnosis of RRMS in accordance with the 2017 revised McDonald criteria.
• The participant must have a current diagnosis of SPMS.
• The participant must have documented evidence of disability progression observed during the 12 months before screening. Eligibility will be analyzed by an Adjudication Committee.
• Absence of clinical relapses for at least 24 months.
• The participant must have an EDSS score at screening from 3.0 to 6.5 points, inclusive.
• The participant must have, at screening, disease duration from the onset of MS symptoms of:
  • < 20 years in participants with EDSS scores at screening > 5.0;
  • < 10 years in participants with EDSS scores at screening ≤ 5.0.
• Male and/or female:
  • Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies;
  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
    • Is not a WOCBP;
    • Is a WOCBP and agrees to use an acceptable contraceptive method during the intervention period;
    • A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) 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;
    • Requirements for pregnancy testing during and after study intervention are located in the SoA;
    • 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, if allowed by local regulations.

Exclusion Criteria:

• The participant has a history of infection or may be at risk for infection:
  • A history of T-lymphocyte or T-lymphocyte-receptor vaccination, transplantation (including solid organ, stem cell, and bone marrow transplantation) and/or antirejection therapy;
  • The participant has received any live (attenuated) vaccine (including but not limited to varicella zoster, oral polio, and nasal influenza) within 2 months before the first treatment visit;
  • The participant has a lymphocyte count less than the lower limit of normal (LLN) at the Screening Visit;
  • A history of diagnosis of progressive multifocal leukoencephalopathy (PML) or evidence of findings suggestive of PML on the screening MRI;
  • A history of infection with human immunodeficiency virus (HIV);
  • A history of active or latent tuberculosis (TB); TB testing should be performed at screening and again during the study, if clinically indicated and maybe repeated based on clinical judgment, borderline results, or clinical suspicion of TB infection. In case of confirmed active or latent TB the patient can be re-screened after full completion of anti-tuberculosis treatment. Further details are described in the Study Manual;
  • NOTE: The Investigator may consult with an infectious disease expert if required; e.g., test results are unclear or there is a suspicion of false-positive test results. If the infectious disease expert considers the test results as false-positive and not clinically relevant and confirms that the participant can be enrolled in the trial, the Investigator must document this in the source data and may then randomize the participant.
  • Persistent chronic or active recurring infection requiring treatment with antibiotics, antivirals, or antifungals;
  • Fever within 4 weeks of the Screening Visit (≥ 38°C; however, if due to brief and mild ear, nose, throat viral infection patient may be included based on the Investigator’s judgment);
  • Participants at risk of developing or having reactivation of hepatitis: results at screening for serological markers for hepatitis B and C indicating acute or chronic infection.
• The presence of psychiatric disturbance or substance abuse as evidenced by:
  • A history of any psychiatric disease, behavioral condition, or depression requiring hospitalization within 2 years prior to the Screening Visit;
  • A documented history of attempted suicide over the 6 months prior to the Screening Visit, presents with suicidal ideation of category 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) during the study, OR if in the Investigator's judgment, the participant is at risk for a suicide attempt;
  • A history of alcohol or drug abuse within 1 year prior to the Screening Visit.
• The following findings obtained during the screening visit considered in the Investigator’s judgment to be clinically significant:
  • Any screening laboratory values outside normal limits;
  • Abnormal ECG.
• Conditions that may predispose the patient to excessive bleeding:
  • 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 had major surgery within 4 weeks prior to the Screening Visit, which could affect the participant’s safety or affect immune response (as judged by the Investigator) or has planned any elective major surgery during the study.
• Conditions that would adversely affect participation in the study or make the primary efficacy endpoint non-evaluable:
  • A short life expectancy due to pre-existing health condition(s) as determined by their treating neurologist;
  • A history or presence of significant other concomitant illness according to the Investigator’s judgment such as, but not limited to cardiovascular (including Stage III or IV cardiac failure according to New York Heart Association [NYHA] classification), or renal (i.e., undergoing dialysis), neurological, endocrine, gastrointestinal, hepatic (i.e., underlying hepatobiliary disease, screening ALT > 3 × upper limit of normal (ULN), or albumin ≤ 2.5 g/dL [25 g/L]), metabolic, pulmonary, or lymphatic disease that would adversely affect participation in this study;
  • Any malignancy within 5 years prior to the Screening visit (except for effectively treated carcinoma in situ of the cervix or adequately treated non-metastatic squamous or basal cell carcinoma of the skin) will also be exclusionary;
  • Any other 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, such as any of the following medications/treatments within the specified time frame before any randomization assessment (no wash out is required for interferon beta or glatiramer acetate treatments although use is not permitted on or after Day 1):
  • Dimethyl fumarate, siponimod 1 month prior to randomization;
  • Intravenous (IV) immunoglobulin, fingolimod 2 months prior to randomization;
  • Teriflunomidea mildly to moderately; immunosuppressive/chemotherapeutic medications such azathioprine, mycophenolate mofetil, and methotrexate 3 months prior to randomization;
  • Natalizumab 6 months prior to randomization;
  • B-cell depleting therapies such as ocrelizumab and rituximab 6 months prior to randomization or until return of B cell counts to normal levels, whichever is longer;
  • Highly immunosuppressive/ chemotherapeutic medications: mitoxantrone up to 120 mg/m2 body surface area, cyclophosphamide, cladribine, cyclosporine 2 years prior to randomization;
  • Alemtuzumab 4 years prior to randomization;
  • Other MS-disease-modifying therapies 5 half-lives or until end of pharmacodynamics activity, whichever is longer;
  • Lymphoid irradiation, bone marrow transplantation, mitoxantrone (with evidence of cardiotoxicity following treatment, or cumulative lifetime dose > 120 mg/m^2), other strongly immunosuppressive treatments with very long-lasting effects. No patient who has received any of these treatments at any time is eligible.
• The participant is receiving strong inducers or inhibitors of CYP3A or CYP2C8 hepatic enzymes.
• The participant is receiving anticoagulant/antiplatelet therapies; those that are not permitted to be taken concomitantly with the IMP, include the following:
  • Acetylsalicylic acid (aspirin);
  • Antiplatelet drugs (e.g., clopidogrel);
  • Warfarin (vitamin K antagonist);
  • Heparin, including low molecular weight heparin (antithrombin agents);
  • Dabigatran (direct thrombin inhibitor);
  • Apixaban, edoxaban, rivaroxaban (direct factor Xa inhibitors);
  • All above drugs need to be stopped at least 5 half-lives before study drug administration except for aspirin, which needs to be stopped at least 8 days before.
• The participant has sensitivity to any of the study interventions, or components thereof, or has a drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.
• The participant was previously exposed to any BTK inhibitor, including SAR442168.
• The participant has taken other investigational drugs within 3 months or 5 half-lives, whichever is longer, before the screening visit.
• The participant has a contraindication for MRI, ie, presence of pacemaker, metallic implants in high risk areas (i.e., artificial heart valves, aneurysm/vessel clips), presence of metallic material (e.g., 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:
  • People with a contraindication to Gd can be enrolled into the study but cannot receive Gd contrast dyes during their MRI scan.
• Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
• Any country-related specific regulation that would prevent the participant from entering the study. (country-specific requirements).
• The participant is not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures or not able to follow the schedule of protocol assessments due to other reasons (exception: participants who are not able to complete electronic clinical outcome assessments may be given paper clinical outcome assessments to complete).
• Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals (in conjunction with Section 1.61 of the International Council for Harmonisation [ICH] - Good Clinical Practice [GCP] Ordinance).
• Any other situation during study implementation/course that may raise ethics considerations.

Eligibility last updated 4/14/22. Questions regarding updates should be directed to the study team contact.