Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 1)

Brief description of study

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

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.

Clinical Study Identifier: NCT04410978

You may be eligible for this study if you meet the following criteria:

  • Conditions: Relapsing Multiple Sclerosis
  • Age: Between 18 Years - 55 Years
  • Gender: Male or Female

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
          -  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
          -  Confirmed screening ALT >2 × ULN
          -  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.

Last updated on 13 May 2022

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