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

NCT ID: NCT05132569

Last Updated: 2025-09-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-03
• Study Completion Date: 2023-02-21

Brief 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.

Detailed 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.

Conditions

Myasthenia Gravis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo/Tolebrutinib

Participants with moderate-to-severe gMG received placebo (matched to tolebrutinib) tablet orally once daily as an add-on therapy to their SoC for 26 weeks in the DB treatment period. Participants who completed the DB period entered the OLE period and received tolebrutinib 60 milligrams (mg) orally daily along with SoC starting from Week 27 up to an additional 35 weeks in the OLE period until the study termination (i.e., up to Week 61).

Group Type: PLACEBO_COMPARATOR

Tolebrutininb

Intervention Type: DRUG

Pharmaceutical form: Film-coated tablet Route of administration: Oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: Film-coated tablet Route of administration: Oral

Tolebrutinib/Tolebrutinib

Participants with moderate-to-severe gMG received tolebrutinib 60 mg tablet orally once daily as an add-on therapy to their SoC for 26 weeks in the DB treatment period. Participants who completed the DB period entered the OLE period and continued to receive tolebrutinib 60 mg orally daily along with SoC starting from Week 27 up to an additional 35 weeks in the OLE period until the study termination (i.e., up to Week 61).

Group Type: EXPERIMENTAL

Tolebrutininb

Intervention Type: DRUG

Pharmaceutical form: Film-coated tablet Route of administration: Oral

Interventions

Tolebrutininb

Pharmaceutical form: Film-coated tablet Route of administration: Oral

Intervention Type: DRUG

Placebo

Pharmaceutical form: Film-coated tablet Route of administration: Oral

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participants were 18 years of age to 85 years of age inclusive, at the time of signing the informed consent.
• Participants with a diagnosis of gMG at screening with generalized muscle weakness meeting the clinical criteria for diagnosis of MG, as defined by the myasthenia gravis foundation of America (MGFA) Clinical Classification Class II, III, or IV, and likely not in need of a respirator for the duration of the study, as judged by the Investigator.
• Positive serologic testing for anti-acetylcholine receptor (anti-AChR) or anti-muscle-specific kinase (anti-MuSK) autoantibody at screening OR
• Seronegative for both anti-AChR and anti-MuSK autoantibodies and with prior diagnosis supported by greater than or equal to (>=) 1 of the following 3 tests:

1. History of abnormal neuromuscular transmission demonstrated by single-fiber electromyography or repetitive nerve stimulation.

2. History of positive edrophonium chloride test.

3. Participant had demonstrated improvement in gMG signs on oral acetylcholinesterase inhibitors as assessed by the treating physician.

• The participant had a total score >=6 on myasthenia gravis-activities of daily living scale at screening and Day 1 with greater than half of the score attributed to non-ocular items.

Exclusion Criteria

• MGFA Class I (ocular MG) or Class V.
• Participants had undergone thymectomy within 6 months of screening or having a planned thymectomy during the trial period.
• The participant had a history of infection or might be at risk for infection: A history of active or latent tuberculosis (TB); Participants at risk of developing or having reactivation of hepatitis; Persistent chronic or active recurring infection required treatment with antibiotics, antivirals, or antifungals; Fever within 4 weeks of 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's judgment); A history of infection with human immunodeficiency virus (HIV); A history of T-lymphocyte or T-lymphocyte-receptor vaccination, transplantation (including solid organ, stem cell, and bone marrow transplantation) and/or antirejection therapy.
• Any malignancy within the past 5 years prior Screening Visit (except for effectively treated carcinoma in situ of the cervix, adequately treated non-metastatic squamous or basal cell carcinoma of the skin and malignant thymoma that had been resected or were considered as cured by any treatment with no evidence of metastatic disease for >=3 years) 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 a participant's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Georgetown University-Site Number:8400008

Washington D.C., District of Columbia, United States

SFM Clinical Research, LLC-Site Number:8400006

Boca Raton, Florida, United States

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

Tampa, Florida, United States

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

Boston, Massachusetts, United States

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

San Antonio, Texas, United States

Investigational Site Number :1240004

Edmonton, Alberta, Canada

Investigational Site Number :1240003

London, Ontario, Canada

Investigational Site Number :1560003

Chengdu, , China

Investigational Site Number :1560001

Shanghai, , China

Investigational Site Number :1560002

Wuhan, , China

Investigational Site Number :3480002

Pécs, , Hungary

Investigational Site Number :3480001

Szeged, , Hungary

Investigational Site Number :3800002

Milan, Lombardy, Italy

Investigational Site Number :3800001

Milan, , Italy

Investigational Site Number :3800004

Napoli, , Italy

Investigational Site Number :3800003

Roma, , Italy

Investigational Site Number :3920002

Sagamihara-shi, Kanagawa, Japan

Investigational Site Number :6160001

Zabrze, , Poland

Investigational Site Number :7240003

L'Hospitalet de Llobregat, Catalunya [Cataluña], Spain

Investigational Site Number :7240005

Madrid, Madrid, Comunidad de, Spain

Investigational Site Number :8260002

Exeter, Devon, United Kingdom

Investigational Site Number :8260001

Liverpool, , United Kingdom

Countries

United States; Canada; China; Hungary; Italy; Japan; Poland; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.trialsummaries.com/Study/StudyDetails?id=25263&tenant=MT_SNY_9011

EFC17262 Plain Language Results Summary

Other Identifiers

U1111-1265-6378

Identifier Type: REGISTRY

Identifier Source: secondary_id

2021-003898-59

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC17262

Identifier Type: -

Identifier Source: org_study_id