Efficacy and safety of tolebrutinib (SAR442168) tablets in adult participants with generalized myasthenia gravis

JRCT ID: jRCT2031220158

Registered date:22/06/2022

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Myasthenia gravis
• Date of first enrollment: 05/07/2022
• Target sample size: 154
• Countries of recruitment: Canada,Japan,China,Japan,Hungary,Japan,Italy,Japan,Poland,Japan,Spainm,Japan,United Kingdo,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Drug: SAR442168 (tolebrutinib)
- Pharmaceutical form: Film-coated tablet, Route of administration: Oral
- Oral daily dose from baseline until Week 130
Drug: Placebo
- Pharmaceutical form: Film-coated tablet, Route of administration: Ora
- Oral daily dose only for double-blind period

Outcome(s)

Primary Outcome

1. Double-blind (DB) period: Change from baseline in Myasthenia gravis-activities of daily living (MG-ADL) total score [ Time Frame: Baseline, Week 26 ]
The MG-ADL is a categorical scale that assesses the impact on daily function of 8 signs symptoms that are typically affected in MG. Each item is assessed on a 4-point scale where a score of 0 represents normal function and a score of 3 represents loss of ability to perform that function (total score 0 to 24).

2. OLE: Number of participants with adverse events (AEs) /SAEs [ Time Frame: From Week 26 until Week 130 ]
Incidence of adverse events (AEs) and serious adverse events (SAEs)

Secondary Outcome

1. Change from baseline in Quantitative MG (QMG) total score [ Time Frame: DB period: Baseline, Week 12, Week 26. OLE: Baseline, Week 130 ]
Quantitative Myasthenia Gravis is clinician-reported outcome/assessment to assess muscle weakness in people with MG. The QMG consists of 13 items ranging from 0 to 3 with 3 being the most severe.

2. Change from baseline in MG Impairment Index (MGII) total score [ Time Frame: DB period: Baseline, Week 26. OLE: Baseline, Week 130 ]
The Myasthenia Gravis Impairment Index (MGII) is a measure of MG impairment focused on the severity of MG impairment and the concept of fatigability. Consists of a 22-item patient-reported questionnaire with 6 clinician assessment items. Higher scores indicate greater disease severity.

3. Change from baseline in MG Quality of Life Questionnaire (MG-QOL15) total score [ Time Frame: DB period: Baseline, Week 26. OLE: Baseline, Week 130 ]
The MG-QoL15 is a 15-item measure of people with MG QoL instrument that will be self-reported by the participant. The domains covered by the questionnaire are mobility (9 items), symptoms (3 items), general contentment (1 item) and emotional well-being (2 items). Responses to each question are scored from 0 (not at all) to 4 (very much) where higher scores representing worse QoL.

4. Proportion of participants with >= 2-point improvement (reduction) in MG-ADL total score [ Time Frame: DB period: From Baseline until Week 26. OLE: From Baseline up to Week 130 ]

5. Proportion of participants with >= 3-point improvement (reduction) in QMG total score [ Time Frame: DB period: From Baseline until Week 26. OLE: From Baseline up to Week 130 ]

6. DB: Number of participants with AEs /SAEs [ Time Frame: From Baseline until Week 26 ]

7. OLE: Change from baseline in MG-ADL total score [ Time Frame: Baseline, Week 130 ]
The MG-ADL is a categorical scale that assesses the impact on daily function of 8 signs symptoms that are typically affected in MG. Each item is assessed on a 4-point scale where a score of 0 represents normal function and a score of 3 represents loss of ability to perform that function (total score 0 to 24).

8. OLE: Proportion of participants achieving any reduction from baseline in daily dose of oral corticosteroids (OCS) [ Time Frame: From Baseline until Week 130 ]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 85age old
• Gender: Both

Include criteria

- Participants must be 18 years of age to 85 years of age inclusive, at the time of signing the informed consent
- Participants with a diagnosis of Generalized myasthenia gravis (gMG) at screening with generalized muscle weakness meeting the clinical criteria for diagnosis of Myasthenia gravis (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 (AChR) or anti-Muscle-specific kinase (MuSK) autoantibody at screening OR
- Seronegative for both anti-AChR and anti-MuSK autoantibodies and with prior diagnosis supported by >=1 of the following 3 tests:
a) History of abnormal neuromuscular transmission demonstrated by single-fiber electromyography or repetitive nerve stimulation
b) History of positive edrophonium chloride test
c) Participant has demonstrated improvement in gMG signs on oral acetylcholinesterase inhibitors as assessed by the treating physician.
- The participant must have a total score >=6 on Myasthenia gravis-activities of daily living (MG-ADL) scale at screening and D1 with greater than half of the score attributed to non-ocular items

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:
- MGFA Class I (ocular MG) or Class V
- Participants having undergone thymectomy within 6 months of screening or having a planned thymectomy during the trial period.
- The participant has a history of infection or may 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 requiring treatment with antibiotics, antivirals, or antifungals; Fever within 4 weeks of the Screening Visit ( >=38C; however, if due to brief and mild ear, nose, throat viral infection participant may 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 have been resected or are considered as cured by any treatment with no evidence of metastatic disease for >=3 years) will be exclusionary
- Conditions that may predispose the participant to excessive bleeding
- Clinically significant laboratory abnormalities (including evidence of liver injury) or electrocardiogram abnormalities at Screening
- The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT05132569,2021-003898-59