Efficacy and Safety of Tolebrutinib (SAR442168) Tablets in Adult Participants With Generalized Myasthenia Gravis (URSA)

Sanofi

Status and phase: Terminated; Phase 3

Conditions: Myasthenia Gravis

Treatments: Drug: Tolebrutininb; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05132569

EFC17262

U1111-1265-6378 (Registry Identifier)

2021-003898-59 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 6 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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6 participants in 2 patient groups, including a placebo group

Placebo/Tolebrutinib

Placebo Comparator group

Description:

Participants with moderate-to-severe gMG received placebo (matched to tolebrutinib) tablet orally once daily as an add-on therapy to their SoC for 26 weeks in the DB treatment period. Participants who completed the DB period entered the OLE period and received tolebrutinib 60 milligrams (mg) orally daily along with SoC starting from Week 27 up to an additional 35 weeks in the OLE period until the study termination (i.e., up to Week 61).

Treatment:

Drug: Placebo

Drug: Tolebrutininb

Tolebrutinib/Tolebrutinib

Experimental group

Description:

Participants with moderate-to-severe gMG received tolebrutinib 60 mg tablet orally once daily as an add-on therapy to their SoC for 26 weeks in the DB treatment period. Participants who completed the DB period entered the OLE period and continued to receive tolebrutinib 60 mg orally daily along with SoC starting from Week 27 up to an additional 35 weeks in the OLE period until the study termination (i.e., up to Week 61).

Treatment:

Drug: Tolebrutininb