URSA: Efficacy and Safety of Tolebrutinib (SAR442168) Tablets in Adult Participants With Generalized Myasthenia Gravis
Study Details
Study Description
Brief Summary
This is 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 gMG, who are receiving Standard of Care (SoC). The double-blind (DB) treatment period of 26 weeks will comprise of 7 site visits followed by a 2-year open label extension (OLE) period with quarterly visits. The efficacy of tolebrutinib versus placebo during DB period will be assessed by clinical evaluations, that include scales based on physician examination or direct participant feedback i.e., patient reported outcomes (PROs). These evaluations will continue during the OLE in order to measure long term efficacy and safety.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
The duration of the DB period will be 26 weeks. The OLE is up to 104 weeks. The duration of the whole study DB+OLE is 130 weeks.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SAR442168 Tolebrutinib oral daily dose from baseline until Week 130 |
Drug: Tolebrutininb
Pharmaceutical form: Film-coated tablet Route of administration: Oral
|
| Placebo Comparator: Placebo Matching placebo oral daily dose only for DB period |
Drug: Placebo
Pharmaceutical form: Film-coated tablet Route of administration: Oral
|
Outcome Measures
Primary Outcome Measures
- DB period: Change from baseline in Myasthenia gravis-activities of daily living (MG-ADL) total score [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).
- OLE: Number of participants with adverse events (AEs) /SAEs [From Week 26 until Week 130]
Incidence of adverse events (AEs) and serious adverse events (SAEs)
Secondary Outcome Measures
- Change from baseline in Quantitative MG (QMG) total score [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.
- Change from baseline in MG Impairment Index (MGII) total score [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.
- Change from baseline in MG Quality of Life Questionnaire (MG-QOL15) total score [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.
- Proportion of participants with ≥ 2-point improvement (reduction) in MG-ADL total score [DB period: From Baseline until Week 26 OLE: From Baseline up to Week 130]
- Proportion of participants with ≥ 3-point improvement (reduction) in QMG total score [DB period: From Baseline until Week 26 OLE: From Baseline up to Week 130]
- DB: Number of participants with AEs /SAEs [From Baseline until Week 26]
- OLE: Change from baseline in MG-ADL total score [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).
- OLE: Proportion of participants achieving any reduction from baseline in daily dose of oral corticosteroids (OCS) [From Baseline until Week 130]
Eligibility Criteria
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:
-
History of abnormal neuromuscular transmission demonstrated by single-fiber electromyography or repetitive nerve stimulation
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History of positive edrophonium chloride test
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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
Exclusion Criteria:
-
MGFA Class I (ocular MG) or Class V
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Participants having undergone thymectomy within 6 months of screening or having a planned thymectomy during the trial period.
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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
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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
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Conditions that may predispose the participant to excessive bleeding
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Clinically significant laboratory abnormalities (including evidence of liver injury) or electrocardiogram abnormalities at Screening
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The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Georgetown University-Site Number:8400008 | Washington | District of Columbia | United States | 20007 |
| 2 | SFM Clinical Research, LLC-Site Number:8400006 | Boca Raton | Florida | United States | 33487 |
| 3 | University of South Florida Health- Morsani Center for Advanced Healthcare-Site Number:8400001 | Tampa | Florida | United States | 33612-6601 |
| 4 | Harvard Medical School - Brigham and Women's Hospital-Site Number:8400004 | Boston | Massachusetts | United States | 02115 |
| 5 | Neurology Center of San Antonio, PA-Site Number:8400009 | San Antonio | Texas | United States | 00000 |
| 6 | Investigational Site Number :1240004 | Edmonton | Alberta | Canada | T6G 2B7 |
| 7 | Investigational Site Number :1240003 | London | Ontario | Canada | N6A 5A5 |
| 8 | Investigational Site Number :1560003 | Chengdu | China | 610041 | |
| 9 | Investigational Site Number :1560001 | Shanghai | China | 200040 | |
| 10 | Investigational Site Number :1560002 | Wuhan | China | 430030 | |
| 11 | Investigational Site Number :3480002 | Pécs | Hungary | 7623 | |
| 12 | Investigational Site Number :3480001 | Szeged | Hungary | 6725 | |
| 13 | Investigational Site Number :3800002 | Milano | Lombardia | Italy | 20133 |
| 14 | Investigational Site Number :3800004 | Napoli | Italy | 80131 | |
| 15 | Investigational Site Number :3800003 | Roma | Italy | 00168 | |
| 16 | Investigational Site Number :3920002 | Sagamihara-shi | Kanagawa | Japan | 252-0392 |
| 17 | Investigational Site Number :6160001 | Zabrze | Poland | 41-800 | |
| 18 | Investigational Site Number :7240001 | Barcelona | Barcelona [Barcelona] | Spain | 08035 |
| 19 | Investigational Site Number :7240005 | Madrid | Madrid, Comunidad De | Spain | 28046 |
| 20 | Investigational Site Number :7240006 | Donostia | Pais Vasco | Spain | 20014 |
| 21 | Investigational Site Number :7240003 | Hospitalet de Llobregat | Spain | 08907 | |
| 22 | Investigational Site Number :8260002 | Exeter | Devon | United Kingdom | EX2 5DW |
| 23 | Investigational Site Number :8260001 | Liverpool | United Kingdom | L9 7LJ |
Sponsors and Collaborators
- Sanofi
Investigators
- Study Director: Clinical Sciences & Operations, Sanofi
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EFC17262
- U1111-1265-6378
- 2021-003898-59