A Randomized, Double-Blind, Multicenter, Placebo-Controlled Phase 3 Study with Open-Label Period to Evaluate the Efficacy and Safety of Inebilizumab in Adults with Myasthenia Gravis (VIB0551.P3.S1)
1. Diagnosis of MG with anti-AChR or anti-MuSK antibody.
2. MGFA Clinical Classification Class II, III, or IV.
3. MG-ADL score of 6 or greater at screening and at randomization with > 50% of this score attributed to non-ocular items.
4. QMG score of 11 or greater.
5. Participants must be on:
a. Corticosteroids only, with no dose increase within 4 weeks prior to randomization, or
b. One allowed non-steroidal immunosuppressive therapy (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.
Tacrolimus is allowed in Japan only, at a dose of <= 3 mg/day, with continued use for at least 6 months prior
to randomization and no dose increase within 4 months prior to randomization.
1. Receipt of the following medications within the 4 weeks prior to Day 1:
a. Cyclosporine (except eye drops)
b. Tacrolimus (except topical) (tacrolimus <= 3 mg/day is allowed in Japan only)
c. Methotrexate
2. Current use of:
a. Corticosteroids (prednisone > 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.
18age 0month 0week old over
No limit
Both
AChR-Ab+ or MuSK-Ab+ generalized Myasthenia Gravis
(RCP: Randomized Controlled Period)
Treatment group 1: AChR-Ab positive population (active) - inebilizumab 300 mg administered intravenously (IV) on Days 1, 15, and 183 of the RCP
Treatment group 2: AChR-Ab positive population (placebo) - IV placebo on Days 1, 15, and 183 of the RCP
Treatment group 3: MuSK-Ab positive population (active) - inebilizumab 300 mg IV on Days 1 and 15 of the 26-week RCP
Treatment group 4: MuSK-Ab positive population (placebo) - IV placebo on Days 1 and 15 of the 26-week RCP
Primary endpoint: Change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score at Week 26 in the overall study population (ie, the AChR-Ab+ and MuSK-Ab+ populations).
Key secondary endpoints:
1. Change from baseline in Quantitative Myasthenia Gravis (QMG) score at Week 26 in the overall study population.
2. Change from baseline in MG-ADL score at Week 26 in the AChR-Ab+ population.
3. Change from baseline in QMG score at Week 26 in the AChR-Ab+ population.
4. Change from baseline in MG-ADL score at Week 26 in the MuSK-Ab+ population.
5. Change from baseline in QMG score at Week 26 in the MuSK-Ab+ population.
Additional secondary endpoints:
1. The proportion of subjects with >= 3-point improvement in MG-ADL score at Week 26 and no use of rescue therapy between Day 28 and Week 26 in the overall study population, the AChR-Ab+ population, and the MuSK-Ab+ population and at Week 52 and no use of rescue therapy between Day 28 and Week 52 in the AChR-Ab+ population.
2. Change from baseline in MG-ADL score at Week 52 in the AChR-Ab+ population.
3. Change from baseline in QMG score at Week 52 in the AChR-Ab+ population.
4. Change from baseline in Myasthenia Gravis Composite (MGC) score at Week 26 in the overall study population, the AChR-Ab+ population, and the MuSK-Ab+ population and at Week 52 in the AChR-Ab+ population.
5. Change from baseline in Myasthenia Gravis Quality of Life-15 revised (MGQOL-15r) score at Week 26 in the overall study population, the AChR-Ab+ population, and the MuSK-Ab+ population and at Week 52 in the AChR-Ab+ population.
6. Patient Global Impression of Change score at Week 26 in the overall study population, the AChR-Ab+ population, and the MuSK-Ab+ population and at Week 52 in the AChR-Ab+ population.
7. Time to first MG exacerbation by Week 26 in the overall study population, the AChR-Ab+ population, and the MuSK-Ab+ population and by Week 52 in the AChR-Ab+ population.
8. The safety and tolerability of inebilizumab as measured by the incidence of treatment-emergent adverse events, adverse events of special interest, and treatment-emergent serious adverse events. Laboratory measurements will also be evaluated as part of safety.
9. The proportion of subjects with steroid tapered to <= 5 mg/day at Week 26 for the overall study population, the AChR-Ab+ population, and the MuSK-Ab+ population and at Week 52 for the AChR-Ab+ population +.
10. The proportion of subjects in whom steroid dose was reduced by >= 50% by Week 26 for the overall study population, the AChR-Ab+ population, and the MuSK-Ab+ population and by Week 52 for the AChR-Ab+ population.
11. The proportion of subjects achieving minimal symptom expression, defined as MG-ADL = 0 or 1, at Week 26.
12. Anti-drug antibody status and titer during the study in the overall study population, the AChR-Ab+ population, and the MuSK-Ab+ population.
Amgen Inc.
General Hanamaki Hospital Institutional Review Board
4-56 Otayacho, Hanamaki-shi, Iwate
+81-198-23-3311
Approval
Dec. 16, 2020
No
NCT04524273
ClinicalTrials.gov
2020-000949-14
EU Clinical Trials Register (EU-CTR)
USA/Ukraine/China/Argentina/Brazil/Canada/France/Denmark/Germany/India/Italy/Poland/Spain/Belarus/Russia/Taiwan/Turkey/South Korea
