Clinical trial NCT05132569: Efficacy and Safety of Tolebrutinib (SAR442168) Tablets in Adult Participants With Generalized Myasthenia Gravis
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Tolebrutinib (SAR442168) in Adults With Generalized Myasthenia Gravis (MG)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Myasthenia Gravis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-11-24
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: DB Period: Change From Baseline in Myasthenia Gravis-activities of Daily Living (MG-ADL) Total Score at Week 26
timeFrame: Baseline (Day 1), Week 26
measure: OLE Period: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Events Leading to Permanent Study Intervention Discontinuation and Adverse Events of Special Interests (AESIs)
timeFrame: From Week 27 up to an additional 35 weeks in the OLE period until the study termination (i.e., up to Week 61)
measure: OLE Period: Number of Participants With Hematological Abnormalities
timeFrame: From Week 27 up to an additional 35 weeks in the OLE period until the study termination (i.e., up to Week 61)
measure: OLE Period: Number of Participants With Clinical Chemistry Parameter Abnormalities
timeFrame: From Week 27 up to an additional 35 weeks in the OLE period until the study termination (i.e., up to Week 61)
measure: OLE Period: Number of Participants With Electrocardiogram (ECG) Abnormalities
timeFrame: From Week 27 up to an additional 35 weeks in the OLE period until the study termination (i.e., up to Week 61)
measure: OLE Period: Number of Participants With Vital Signs Abnormalities
timeFrame: From Week 27 up to an additional 35 weeks in the OLE period until the study termination (i.e., up to Week 61)
Secondary outcomes:
measure: DB Period: Change From Baseline in Quantitative Myasthenia Gravis (QMG) Total Score at Week 26
timeFrame: Baseline (Day 1), Week 26
measure: DB Period: Change From Baseline in Quantitative Myasthenia Gravis (QMG) Total Score at Week 12
timeFrame: Baseline (Day 1), Week 12
measure: DB Period: Change From Baseline in Myasthenia Gravis Impairment Index (MGII) Total Score at Week 26
timeFrame: Baseline (Day 1), Week 26
measure: DB Period: Change From Baseline in Myasthenia Gravis-quality of Life 15-item Scale (MG-QoL15) Total Score at Week 26
timeFrame: Baseline (Day 1), Week 26
measure: DB Period: Percentage of Participants With Greater Than Equal to (>=) 2-point Improvement (Reduction) in Myasthenia Gravis-activities of Daily Living Total Score at Week 26
timeFrame: Week 26
measure: DB Period: Percentage of Participants With >=3-point Improvement (Reduction) in Quantitative Myasthenia Gravis Total Score at Week 26
timeFrame: Week 26
measure: DB Period: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Events Leading to Permanent Study Intervention Discontinuation and Adverse Events of Special Interests (AESIs)
timeFrame: From Day 1 up to Week 26
measure: DB Period: Number of Participants With Hematological Abnormalities
timeFrame: From Day 1 up to Week 26
measure: DB Period: Number of Participants With Clinical Chemistry Parameter Abnormalities
timeFrame: From Day 1 up to Week 26
measure: DB Period: Number of Participants With Electrocardiogram Abnormalities
timeFrame: From Day 1 up to Week 26
measure: DB Period: Number of Participants With Vital Signs Abnormalities
timeFrame: From Day 1 up to Week 26
measure: OLE Period: Change From Baseline in Myasthenia Gravis-activities of Daily Living Total Score
timeFrame: From Week 27 up to an additional 35 weeks in the OLE period until the study termination (i.e., up to Week 61)
measure: OLE Period: Change From Baseline in Quantitative Myasthenia Gravis Total Score
timeFrame: From Week 27 up to an additional 35 weeks in the OLE period until the study termination (i.e., up to Week 61)
measure: OLE Period: Change From Baseline in Myasthenia Gravis Impairment Index Total Score
timeFrame: From Week 27 up to an additional 35 weeks in the OLE period until the study termination (i.e., up to Week 61)
measure: OLE Period: Change From Baseline in Myasthenia Gravis-quality of Life 15-item Scale Total Score
timeFrame: From Week 27 up to an additional 35 weeks in the OLE period until the study termination (i.e., up to Week 61)
measure: OLE Period: Percentage of Participants With >=2-point Improvement (Reduction) in Myasthenia Gravis-activities of Daily Living Total Score
timeFrame: From Week 27 up to an additional 35 weeks in the OLE period until the study termination (i.e., up to Week 61)
measure: OLE Period: Percentage of Participants With >=3-point Improvement (Reduction) in Quantitative Myasthenia Gravis Total Score
timeFrame: From Week 27 up to an additional 35 weeks in the OLE period until the study termination (i.e., up to Week 61)
measure: OLE Period: Percentage of Participants Achieving Any Reduction From Baseline of Daily Dose of Oral Corticosteroids (OCS) at Week 61
timeFrame: Baseline (Day 1), Week 61
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University-Site Number:8400008
state: District of Columbia
city: Boca Raton
country: United States
facility: SFM Clinical Research, LLC-Site Number:8400006
state: Florida
city: Tampa
country: United States
facility: University of South Florida Health- Morsani Center for Advanced Healthcare-Site Number:8400001
state: Florida
city: Boston
country: United States
facility: Harvard Medical School - Brigham and Women's Hospital-Site Number:8400004
state: Massachusetts
city: San Antonio
country: United States
facility: Neurology Center of San Antonio, PA-Site Number:8400009
state: Texas
city: Edmonton
country: Canada
facility: Investigational Site Number :1240004
state: Alberta
city: London
country: Canada
facility: Investigational Site Number :1240003
state: Ontario
city: Chengdu
country: China
facility: Investigational Site Number :1560003
city: Shanghai
country: China
facility: Investigational Site Number :1560001
city: Wuhan
country: China
facility: Investigational Site Number :1560002
city: Pécs
country: Hungary
facility: Investigational Site Number :3480002
city: Szeged
country: Hungary
facility: Investigational Site Number :3480001
city: Milano
country: Italy
facility: Investigational Site Number :3800002
state: Lombardia
city: Milano
country: Italy
facility: Investigational Site Number :3800001
city: Napoli
country: Italy
facility: Investigational Site Number :3800004
city: Roma
country: Italy
facility: Investigational Site Number :3800003
city: Sagamihara-shi
country: Japan
facility: Investigational Site Number :3920002
state: Kanagawa
city: Zabrze
country: Poland
facility: Investigational Site Number :6160001
city: Hospitalet de Llobregat
country: Spain
facility: Investigational Site Number :7240003
state: Catalunya [Cataluña]
city: Madrid
country: Spain
facility: Investigational Site Number :7240005
state: Madrid, Comunidad De
city: Exeter
country: United Kingdom
facility: Investigational Site Number :8260002
state: Devon
city: Liverpool
country: United Kingdom
facility: Investigational Site Number :8260001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: