Myasthenia Gravis which is either due to acetylcholine receptor antibodies (AChR) or muscle specific kinase antibodies (MuSK). MedDRA version: 21.1 Level: PT Classification code 10028417 Term: Myasthenia gravis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Uplizna
Product Name: Inebilizumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: INEBILIZUMAB
Current Sponsor code: VIB0551
Other descriptive name: CD19-d
Sponsors
Viela Bio, Inc./Horizon Therapeutics Ireland DAC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Diagnosis of MG with anti-AChR or anti-MuSK antibody. 2.MGFA Clinical Classification Class II, III, or IV. 3.MG-ADL score at the time of screening and randomization between 6 and 10 with > 50% of this score attributed to non-ocular items, or an MG-ADL score = 11. 4.QMG score of 11 or greater at the time of screening and at randomization. 5.Subjects must be on: a. Corticosteroids only, with no dose increase within 4 weeks prior to randomization, or b. One allowed non-steroidal IST, with continuous use for at least 6 months prior to randomization and no dose increase within 4 months prior to randomization, or c. Combination of (1) corticosteroids with no dose increase within 4 weeks prior to randomization and (2) one allowed non-steroidal IST with continuous use for at least 6 months prior to randomization and no dose increase within 4 months prior to randomization. Allowed ISTs, alone or in combination with corticosteroids, are azathioprine, mycophenolate mofetil, and mycophenolic acid. 6. 9. Females of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective contraception method from the time of screening and for 6 months after the final dose of IP. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 230 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 8. Thymectomy within = 12 months prior to baseline (Day 1) visit or planned thymectomy during the duration of the RCP. 9. Receipt of the following medications or treatments at any time prior to randomization: a. Alemtuzumab b. Total lymphoid irradiation c. Bone marrow transplant d. T-cell vaccination therapy e. Natalizumab 10. Receipt of rituximab, ocrelizumab, ofatumumab, obinutuzumab, inebilizumab, or any experimental B-cell depleting agent within the 6 months prior to Day 1, unless the subject has a CD19+ B-cell count = 40 cells/µL according to the central laboratory at screening. 11. Receipt of Leflunomide within 1 year prior to Day 1. 12. Receipt within the 3 months prior to Day 1: a. Tocilizumab b. Belimumab c. Eculizumab d. Cyclophosphamide e. Ravulizumab f. Neonatal fragment crystallizable (Fc) receptor (FcRn) blockers (efgartigimod alfa) g. Abatacept h. Etanercept i. Mitoxantrone j. Sirolimus 13. Receipt within the 4 weeks prior to Day 1: a. Cyclosporine (except eye drops) b. Tacrolimus (except topical) (tacrolimus 40 mg/day or > 80 mg over a 2-day period, or equivalent dose of other corticosteroids) b. Acetylcholinesterase inhibitors (pyridostigmine > 480 mg/day) or unstable dose in the 2 weeks prior to Day 1 c. Azathioprine > 3 mg/kg/day d. Mycophenolate mofetil > 3 g/day or mycophenolic acid > 1440 mg/day e. Any IST, alone or in combination with corticosteroids, except for azathioprine, mycophenolate mofetil, and mycophenolic acid. 15. Concurrent/previous enrollment in another clinical study involving an investigational treatment within 4 weeks or 5 half-lives of the investigational treatment, whichever is longer, prior to Day 1. 16. Receipt of a live attenuated vaccine within 4 weeks prior to randomization. Administration of inactivated (killed) vaccines is acceptable. 25. History of untreated hepatitis C infection, or positive antibody test for hepatitis C virus (HCV) unless patient is considered to be cured following antiviral therapy and has a HCV viral load below the limit of detection at least 24 weeks after completion of treatment at site or central lab 30. Hospitalization for any reason less than 30 days prior to randomization 31. Current or recent myasthenia gravis exacerbationdeterioration that has not returned to baseline/resolved within at least 30 days prior to randomization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess whether inebilizumab can reduce MG-related disability.;Secondary Objective: - To evaluate whether inebilizumab can reduce the frequency of MG exacerbations. - To evaluate whether inebilizumab can improve MG-related quality of life. - To evaluate the safety and tolerability of inebilizumab in MG. - To characterize the pharmacokinetic (PK) profile and immunogenicity of inebilizumab in patients with MG.;Primary end point(s): Change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) Profile score at end of the RCP;Timepoint(s) of evaluation of this end point: Week 52 for AChR-Ab+ population and Week 26 for MuSK-Ab+ population | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Week 52 for AChR-Ab+ population and Week 26 for MuSK-Ab+ population;Secondary end point(s): Key secondary endpoints: - Change in Quantitative Myasthenia Gravis (QMG) scores at the end of the RCP. - Proportion of subjects with both (1) = 3-point improvement in MG-ADL at end of RCP and (2) For AChR-Ab+ Population: did not initiate rescue therapy between Week 44 and Week 52 during the RCP; For MuSK-Ab+ population: did not initiate rescue therapy between Week 22 and Week 26 during the RCP - Change in MG-ADL at Week 26 in the AChR-Ab+ population. Additional secondary endpoints: - Time to first exacerbation. - Change in Myasthenia Gravis Composite (MGC) score. - Change in Myasthenia Gravis Quality of Life-15, revised (MGQOL-15r) score . - Change in Patient Global Impression of Change (PGIC) score. - The safety and tolerability of inebilizumab as measured by the incidence of TEAEs, adverse events of special interest (AESIs), and TESAEs. Laboratory measurements will also be evaluated as part of safety. - PK profile of inebilizumab. - ADA status and titer. | — |
Countries
Argentina, Belarus, Brazil, Canada, China, Denmark, France, Germany, India, Israel, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactDave Caraher
Viela Bio, Inc./Horizon Therapeutics Ireland DAC
Outcome results
None listed