Back to resultsEfficacy and Safety of Tolebrutinib (SAR442168) Tablets in Adult Participants With Generalized Myasthenia Gravis (URSA)
Primary Purpose
Myasthenia Gravis
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Tolebrutininb
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Myasthenia Gravis
Eligibility 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
- History of positive edrophonium chloride test
- 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
- 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
- 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.
Sites / Locations
- Georgetown University-Site Number:8400008
- SFM Clinical Research, LLC-Site Number:8400006
- University of South Florida Health- Morsani Center for Advanced Healthcare-Site Number:8400001
- Harvard Medical School - Brigham and Women's Hospital-Site Number:8400004
- Neurology Center of San Antonio, PA-Site Number:8400009
- Investigational Site Number :1240004
- Investigational Site Number :1240003
- Investigational Site Number :1560003
- Investigational Site Number :1560001
- Investigational Site Number :1560002
- Investigational Site Number :3480002
- Investigational Site Number :3480001
- Investigational Site Number :3800002
- Investigational Site Number :3800001
- Investigational Site Number :3800004
- Investigational Site Number :3800003
- Investigational Site Number :3920002
- Investigational Site Number :6160001
- Investigational Site Number :7240003
- Investigational Site Number :7240005
- Investigational Site Number :8260002
- Investigational Site Number :8260001
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
SAR442168
Placebo
Arm Description
Tolebrutinib oral daily dose from baseline until Week 130
Matching placebo oral daily dose only for DB period
Outcomes
Primary Outcome Measures
DB period: Change from baseline in Myasthenia gravis-activities of daily living (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).
OLE: Number of participants with adverse events (AEs) /SAEs
Incidence of adverse events (AEs) and serious adverse events (SAEs)
Secondary Outcome Measures
Change from baseline in Quantitative MG (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.
Change from baseline in MG Impairment Index (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.
Change from baseline in MG Quality of Life Questionnaire (MG-QOL15) total 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). 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
Proportion of participants with ≥ 3-point improvement (reduction) in QMG total score
DB: Number of participants with AEs /SAEs
OLE: 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).
OLE: Proportion of participants achieving any reduction from baseline in daily dose of oral corticosteroids (OCS)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05132569
Brief Title
Efficacy and Safety of Tolebrutinib (SAR442168) Tablets in Adult Participants With Generalized Myasthenia Gravis
Acronym
URSA
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
2. Study Status
Record Verification Date
March 8, 2023
Overall Recruitment Status
Terminated
Why Stopped
For strategic reasons the Tolebrutinib MG study has been terminated
Study Start Date
December 3, 2021 (Actual)
Primary Completion Date
February 21, 2023 (Actual)
Study Completion Date
February 21, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myasthenia Gravis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SAR442168
Arm Type
Experimental
Arm Description
Tolebrutinib oral daily dose from baseline until Week 130
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo oral daily dose only for DB period
Intervention Type
Drug
Intervention Name(s)
Tolebrutininb
Intervention Description
Pharmaceutical form: Film-coated tablet Route of administration: Oral
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Pharmaceutical form: Film-coated tablet Route of administration: Oral
Primary Outcome Measure Information:
Title
DB period: Change from baseline in Myasthenia gravis-activities of daily living (MG-ADL) total score
Description
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).
Time Frame
Baseline, Week 26
Title
OLE: Number of participants with adverse events (AEs) /SAEs
Description
Incidence of adverse events (AEs) and serious adverse events (SAEs)
Time Frame
From Week 26 until Week 130
Secondary Outcome Measure Information:
Title
Change from baseline in Quantitative MG (QMG) total score
Description
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.
Time Frame
DB period: Baseline, Week 12, Week 26 OLE: Baseline, Week 130
Title
Change from baseline in MG Impairment Index (MGII) total score
Description
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.
Time Frame
DB period: Baseline, Week 26 OLE: Baseline, Week 130
Title
Change from baseline in MG Quality of Life Questionnaire (MG-QOL15) total score
Description
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.
Time Frame
DB period: Baseline, Week 26 OLE: Baseline, Week 130
Title
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
Title
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
Title
DB: Number of participants with AEs /SAEs
Time Frame
From Baseline until Week 26
Title
OLE: Change from baseline in MG-ADL total score
Description
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).
Time Frame
Baseline, Week 130
Title
OLE: Proportion of participants achieving any reduction from baseline in daily dose of oral corticosteroids (OCS)
Time Frame
From Baseline until Week 130
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility 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
History of positive edrophonium chloride test
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
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
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Georgetown University-Site Number:8400008
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
SFM Clinical Research, LLC-Site Number:8400006
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33487
Country
United States
Facility Name
University of South Florida Health- Morsani Center for Advanced Healthcare-Site Number:8400001
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612-6601
Country
United States
Facility Name
Harvard Medical School - Brigham and Women's Hospital-Site Number:8400004
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Neurology Center of San Antonio, PA-Site Number:8400009
City
San Antonio
State/Province
Texas
ZIP/Postal Code
00000
Country
United States
Facility Name
Investigational Site Number :1240004
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
Investigational Site Number :1240003
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
Investigational Site Number :1560003
City
Chengdu
ZIP/Postal Code
610041
Country
China
Facility Name
Investigational Site Number :1560001
City
Shanghai
ZIP/Postal Code
200040
Country
China
Facility Name
Investigational Site Number :1560002
City
Wuhan
ZIP/Postal Code
430030
Country
China
Facility Name
Investigational Site Number :3480002
City
Pécs
ZIP/Postal Code
7623
Country
Hungary
Facility Name
Investigational Site Number :3480001
City
Szeged
ZIP/Postal Code
6725
Country
Hungary
Facility Name
Investigational Site Number :3800002
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20133
Country
Italy
Facility Name
Investigational Site Number :3800001
City
Milano
ZIP/Postal Code
20132
Country
Italy
Facility Name
Investigational Site Number :3800004
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Investigational Site Number :3800003
City
Roma
ZIP/Postal Code
00168
Country
Italy
Facility Name
Investigational Site Number :3920002
City
Sagamihara-shi
State/Province
Kanagawa
ZIP/Postal Code
252-0392
Country
Japan
Facility Name
Investigational Site Number :6160001
City
Zabrze
ZIP/Postal Code
41-800
Country
Poland
Facility Name
Investigational Site Number :7240003
City
Hospitalet de Llobregat
State/Province
Catalunya [Cataluña]
ZIP/Postal Code
08907
Country
Spain
Facility Name
Investigational Site Number :7240005
City
Madrid
State/Province
Madrid, Comunidad De
ZIP/Postal Code
28046
Country
Spain
Facility Name
Investigational Site Number :8260002
City
Exeter
State/Province
Devon
ZIP/Postal Code
EX2 5DW
Country
United Kingdom
Facility Name
Investigational Site Number :8260001
City
Liverpool
ZIP/Postal Code
L9 7LJ
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Learn more about this trial
Efficacy and Safety of Tolebrutinib (SAR442168) Tablets in Adult Participants With Generalized Myasthenia Gravis
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