Myasthenia gravis MedDRA version: 21.1 Level: PT Classification code 10028417 Term: Myasthenia gravis System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Sanofi-Aventis Recherche & Développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion 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 gMG at screening with generalized muscle weakness meeting the clinical criteria for diagnosis of MG, as defined by the 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-AChR or anti-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 MG-ADL scale at screening and D1 with greater than half of the score attributed to non-ocular items Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 160 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 32
Exclusion criteria
Exclusion 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 (=38°C; 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 - Confirmed screening ALT >3 × ULN - The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: DB period: • To evaluate the efficacy of tolebrutinib compared to placebo as measured by myasthenia gravis-activities of daily living (MG-ADL) score in participants with gMG who are receiving SoC OLE: • To evaluate the long-term safety and tolerability of tolebrutinib in participants with gMG who are receiving SoC;Secondary Objective: DB period: • To evaluate the efficacy of tolebrutinib compared to placebo on additional efficacy measurements: Quantitative MG (QMG), MG Impairment Index (MGII), MG quality of life 15-item Scale (MG-QOL15), MG-ADL in participants with gMG who are receiving SoC • To evaluate the safety and tolerability of tolebrutinib compared to placebo in participants with gMG who are receiving SoC OLE: • To evaluate the long-term efficacy of tolebrutinib in participants with gMG who are receiving SoC;Primary end point(s): 1 - DB period: Change from baseline in MG-ADL total score ; 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 ; Incidence of adverse events (AEs) and serious adverse events (SAEs);Timepoint(s) of evaluation of this end point: 1 : Baseline, Week 26 2 : From Week 26 until Week 130 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 - Change from baseline in QMG total score ; 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 MGII total score ; 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-QOL15 survey score ; 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). 4 - Proportion of participants with = 2-point reduction from baseline in MG-ADL total score 5 - Proportion of participants with = 3-point reduction from baseline in QMG total score 6 - DB: Number of participants with AEs /SAEs 7 - OLE: Change from baseline in MG-ADL total score 8 - OLE: Proportion of participants achieving a reduction from baseline in daily dose of oral corticosteroids (OCS);Timepoint(s) of evaluation of this end point: 1, 2, 3 : DB period: Baseline, Week 26 OLE: Baseline, Week 130 4, 5 : DB period: From Baseline until Week 26 OLE: From Baseline until Week 130 6 : From Baseline until Week 26 7 : Baseline, Week 130 8 : From Baseline until Week 130 | — |
Countries
Canada, China, Germany, Hungary, Italy, Japan, Poland, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactUnidad de Estudios Clínicos
Sanofi-Aventis, S.A
Outcome results
None listed