Generalized Myasthenia Gravis
Conditions
Keywords
Myasthenia Gravis, gMG
Brief summary
The purpose of this study is to evaluate the efficacy and safety of telitacicept in the treatment of generalized myasthenia gravis.
Detailed description
Myasthenia gravis (MG) is an autoimmune disease in which autoantibodies disrupt the postsynaptic membrane, impairing nerve-to-muscle signal transmission. The predominant manifestation is muscle weakness, which typically worsens with repeated muscle exertion, such that function is usually the best in the morning with more pronounced weakness at the end of the day. A major challenge in MG is the lack of therapies that effectively treat the disease. Telitacicept is a fully human TACI-Fc fusion protein that targets B-lymphocyte stimulator (BLyS) and A proliferating-inducing ligand (APRIL), neutralizing their interactions with receptors on B cells. The blockage of BLyS and APRIL interaction with their respective cell membrane receptors (transmembrane activator and CAML interactor \[TACI\], B-cell maturation antigen, and BLyS receptors) by telitacicept can inhibit B-cell proliferation and maturation. This suppression at the proximal portion of the immune response could alleviate autoimmune symptoms. This is a randomized, double-blind, placebo-controlled Phase 3 study with an open-label extension (OLE) to evaluate the efficacy and safety of telitacicept in a global patient population with gMG. The total duration of the study is variable but will include an approximately 4-week screening period, a 24-week double-blind treatment period (Week 0 through Week 24), a 48-week OLE (Week 24 through Week 72), followed by an extended OLE period (E-OLE), and an 8-week end-of-study follow-up period. The E-OLE is variable duration, defined as the period after the 48-week OLE period until telitacicept is approved for MG in the country or the further development in the indication is concluded.
Interventions
BIOLOGICALTelitacicept
Subcutaneous injection
DRUGPlacebo
Subcutaneous injection
Sponsors
Vor Biopharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Male or female patient aged ≥18 years at screening. 2. Patients have prior confirmed diagnosis of gMG with generalized muscle weakness (typical pattern of weakness meeting the clinical criteria for diagnosis of MG as defined by the Myasthenia Gravis Foundation of America (MGFA) clinical classification II-IV. 3. Patients have positive antibodies against AChR or MuSK at screening. 4. MG-ADL score ≥6 points at screening and baseline with ocular-related score \<50% of the total score. 5. QMG score ≥8 points, and ≥ 4 items score at least 2 points at screening and baseline. Key
Exclusion criteria
1. Patients have been diagnosed with any other autoimmune disease which can potentially pose a safety or efficacy confounding risk. 2. Patients having acute or chronic infection. 3. Patients having thymoma within 5 years or received thymectomy ≤6 months prior to screening. Patients with thymoma diagnosed 3-5 years prior to screening may be eligible if thymoma was at a localized stage and definitively treated with complete surgical resection. 4. Patients having current or history of primary immunodeficiency. 5. Patients having history of malignancy within the last 5 years. 6. Patient having prior or continuing diagnosis of serious cardiovascular, liver, kidney, respiratory system, endocrine or hematologic disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score at Week 24 | Week 24 | The MG-ADL is an 8-item patient-reported outcome measure assessing MG symptoms and their effects on daily activities. Each item in the scale is scored on a 0 to 3 (0=normal, 3=severe disease) point scale. The total score is the sum of all individual item scores ranging from 0 to 24. Higher scores indicate more severe disability due to MG. A decrease from Baseline score indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in Quantitative Myasthenia Gravis (QMG) score at Week 24 | Week 24 | The QMG is a standardized and validated quantitative strength scoring system that was developed specifically for MG. The scale consists of 13 items. Each item in the scale is scored on a 0 to 3-point scale, ranging from 0 (no weakness) to 3 (severe weakness), summing up to the overall score range from 0 to 39. Higher scores indicate more severe impairment. A decrease from Baseline score indicates improvement. |
| Change from baseline in MG Quality of Life scale (MG-QOL15r) at Week 24 | Week 24 | The MG-QoL15r is a 15-item patient-reported outcome measure designed to assess quality of life in patients with MG. Each item in the scale is scored on a 0 to 2-point scale (0=Not at all, 1=Somewhat, 2=Very much). The total score is the sum of the 15 individual item scores, ranging from 0 to 30. Higher scores indicate more severe impact of the disease on aspects of the patient's life. A decrease from Baseline score indicates improvement. |
| Proportion of patients with a decrease of ≥2 points from baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score at Week 24 | Week 24 | Proportion of patients with a decrease of ≥2 points from baseline in MG-ADL score at Week 24. The MG-ADL is an 8-item patient-reported outcome measure assessing MG symptoms and their effects on daily activities. Each item in the scale is scored on a 0 to 3 (0=normal, 3=severe disease) point scale. The total score is the sum of all individual item scores ranging from 0 to 24. Higher scores indicate more severe disability due to MG. |
| Proportion of patients with a decrease of ≥3 points from baseline in Quantitative Myasthenia Gravis (QMG) score at Week 24 | Week 24 | Proportion of patients with a decrease of ≥3 points from baseline in QMG score at Week 24. The QMG is a standardized and validated quantitative strength scoring system that was developed specifically for MG. The scale consists of 13 items. Each item in the scale is scored on a 0 to 3-point scale, ranging from 0 (no weakness) to 3 (severe weakness), summing up to the overall score range from 0 to 39. Higher scores indicate more severe impairment. A decrease from Baseline score indicates improvement. |
| Proportion of patients who achieved minimal symptomatic expression (MSE, defined as having MG-ADL score of 0 or 1) at Week 24 | Week 24 | Proportion of patients who achieved minimal symptomatic expression (MSE, defined as having MG-ADL score of 0 or 1) at Week 24 |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Czechia, France, Georgia, Italy, Japan, Poland, Spain, United States
Contacts
CONTACTJeremy Sokolove
Outcome results
None listed