Efficacy and Safety of Tolebrutinib (SAR442168) Tablets in Adult Participants With Generalized Myasthenia Gravis

Last updated: April 4, 2024
Sponsor: Sanofi
Overall Status: Terminated

Phase

3

Condition

Sarcopenia

Neuropathy

Polymyositis (Inflammatory Muscle Disease)

Treatment

Tolebrutininb

Placebo

Clinical Study ID

NCT05132569
EFC17262
2021-003898-59
U1111-1265-6378
  • Ages 18-85
  • All Genders

Study Summary

This was a multicenter, randomized, double-blind, placebo-controlled, Phase 3 study to evaluate the efficacy and safety of tolebrutinib compared with placebo in adult participants aged 18 to 85 years old with moderate-to-severe generalized myasthenia gravis (gMG), who received Standard of Care (SoC). The double-blind (DB) treatment period of 26 weeks comprised of 7 site visits followed by a 2-year open label extension (OLE) period with quarterly visits. The efficacy of tolebrutinib versus placebo during the DB period was assessed by clinical evaluations, including scales based on physician examination or direct participant feedback i.e., patient reported outcomes (PROs). These evaluations continued during the OLE to measure long term efficacy and safety.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Participants were 18 years of age to 85 years of age inclusive, at the time of signingthe informed consent.
  • Participants with a diagnosis of gMG at screening with generalized muscle weaknessmeeting the clinical criteria for diagnosis of MG, as defined by the myasthenia gravisfoundation of America (MGFA) Clinical Classification Class II, III, or IV, and likelynot in need of a respirator for the duration of the study, as judged by theInvestigator.
  • Positive serologic testing for anti-acetylcholine receptor (anti-AChR) oranti-muscle-specific kinase (anti-MuSK) autoantibody at screening OR
  • Seronegative for both anti-AChR and anti-MuSK autoantibodies and with prior diagnosissupported by greater than or equal to (>=) 1 of the following 3 tests:
  1. History of abnormal neuromuscular transmission demonstrated by single-fiberelectromyography or repetitive nerve stimulation.
  2. History of positive edrophonium chloride test.
  3. Participant had demonstrated improvement in gMG signs on oralacetylcholinesterase inhibitors as assessed by the treating physician.
  • The participant had a total score >=6 on myasthenia gravis-activities of daily livingscale at screening and Day 1 with greater than half of the score attributed tonon-ocular items.

Exclusion

Exclusion Criteria:

  • MGFA Class I (ocular MG) or Class V.
  • Participants had undergone thymectomy within 6 months of screening or having a plannedthymectomy during the trial period.
  • The participant had a history of infection or might be at risk for infection: Ahistory of active or latent tuberculosis (TB); Participants at risk of developing orhaving reactivation of hepatitis; Persistent chronic or active recurring infectionrequired treatment with antibiotics, antivirals, or antifungals; Fever within 4 weeksof the Screening Visit (>=38 degree Celsius; however, if due to brief and mild ear,nose, throat viral infection participant might be included based on the Investigator'sjudgment); A history of infection with human immunodeficiency virus (HIV); A historyof T-lymphocyte or T-lymphocyte-receptor vaccination, transplantation (including solidorgan, stem cell, and bone marrow transplantation) and/or antirejection therapy.
  • Any malignancy within the past 5 years prior Screening Visit (except for effectivelytreated carcinoma in situ of the cervix, adequately treated non-metastatic squamous orbasal cell carcinoma of the skin and malignant thymoma that had been resected or wereconsidered as cured by any treatment with no evidence of metastatic disease for >=3years) will be exclusionary.
  • Conditions that might predispose the participant to excessive bleeding.
  • Clinically significant laboratory abnormalities (including evidence of liver injury)or electrocardiogram abnormalities at Screening. The above information was not intended to contain all considerations relevant to aparticipant's potential participation in a clinical trial.

Study Design

Total Participants: 6
Treatment Group(s): 2
Primary Treatment: Tolebrutininb
Phase: 3
Study Start date:
December 03, 2021
Estimated Completion Date:
February 21, 2023

Study Description

The duration of the DB period was 26 weeks. The OLE was planned up to 104 weeks. The duration of the whole study DB+OLE was planned up to130 weeks.

Connect with a study center

  • Investigational Site Number :1240004

    Edmonton, Alberta T6G 2B7
    Canada

    Site Not Available

  • Investigational Site Number :1240003

    London, Ontario N6A 5A5
    Canada

    Site Not Available

  • Investigational Site Number :1560003

    Chengdu, 610041
    China

    Site Not Available

  • Investigational Site Number :1560001

    Shanghai, 200040
    China

    Site Not Available

  • Investigational Site Number :1560002

    Wuhan, 430030
    China

    Site Not Available

  • Investigational Site Number :3480002

    Pécs, 7623
    Hungary

    Site Not Available

  • Investigational Site Number :3480001

    Szeged, 6725
    Hungary

    Site Not Available

  • Investigational Site Number :3800002

    Milano, Lombardia 20133
    Italy

    Site Not Available

  • Investigational Site Number :3800001

    Milano, 20132
    Italy

    Site Not Available

  • Investigational Site Number :3800004

    Napoli, 80131
    Italy

    Site Not Available

  • Investigational Site Number :3800003

    Roma, 00168
    Italy

    Site Not Available

  • Investigational Site Number :3920002

    Sagamihara-shi, Kanagawa 252-0392
    Japan

    Site Not Available

  • Investigational Site Number :6160001

    Zabrze, 41-800
    Poland

    Site Not Available

  • Investigational Site Number :7240001

    Barcelona, Barcelona [Barcelona] 08035
    Spain

    Site Not Available

  • Investigational Site Number :7240003

    Hospitalet de Llobregat, Catalunya [Cataluña] 08907
    Spain

    Site Not Available

  • Investigational Site Number :7240005

    Madrid, Madrid, Comunidad De 28046
    Spain

    Site Not Available

  • Investigational Site Number :7240006

    Donostia, Pais Vasco 20014
    Spain

    Site Not Available

  • Investigational Site Number :8260002

    Exeter, Devon EX2 5DW
    United Kingdom

    Site Not Available

  • Investigational Site Number :8260001

    Liverpool, L9 7LJ
    United Kingdom

    Site Not Available

  • Georgetown University-Site Number:8400008

    Washington, District of Columbia 20007
    United States

    Site Not Available

  • SFM Clinical Research, LLC-Site Number:8400006

    Boca Raton, Florida 33487
    United States

    Site Not Available

  • University of South Florida Health- Morsani Center for Advanced Healthcare-Site Number:8400001

    Tampa, Florida 33612-6601
    United States

    Site Not Available

  • Harvard Medical School - Brigham and Women's Hospital-Site Number:8400004

    Boston, Massachusetts 02115
    United States

    Site Not Available

  • Neurology Center of San Antonio, PA-Site Number:8400009

    San Antonio, Texas 00000
    United States

    Site Not Available

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