Generalized Myasthenia Gravis
Conditions
Keywords
Generalized Myasthenia Gravis, Inebilizumab, AMG 335, Uplizna
Brief summary
The primary objectives of this study are to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of inebilizumab administered in pediatric participants with gMG, and to assess the safety and tolerability of inebilizumab administered in pediatric participants with gMG.
Interventions
DRUGInebilizumab
Inebilizumab will be administered IV.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Participant's legally authorized representative has provided informed consent when the participant is legally too young to provide informed consent and the participant has provided written assent based on local regulations and/or guidelines before any study-specific activities/procedures being initiated. * Age ≥ 2 to \< 18 years of age on the day of enrollment. * Diagnosis of gMG defined as: * Positive serologic test for anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody (Ab) titers as confirmed at screening (1 retest allowed), and * At least 1 of the following: * History of abnormal neuromuscular transmission test results demonstrated by single-fiber electromyography or repetitive nerve stimulation; or * History of positive anticholinesterase test (eg, edrophonium chloride test); or * Participant demonstrated improvement in gMG signs on oral cholinesterase inhibitors, as assessed by the treating physician; or * Clinical syndrome consistent with a diagnosis of gMG, and not otherwise explained by another condition. * Myasthenia Gravis Foundation of America Clinical Classification Class II, III, or IV at the time of screening. * Quantitative Myasthenia Gravis score of 11 or greater at screening. * Participants must be on: * Corticosteroids only, with no dose increase within 4 weeks prior to screening, or * One allowed non-steroidal immunosuppressive therapies (IST) (azathioprine, mycophenolate mofetil, or mycophenolic acid) with continuous use for at least 6 months prior to screening and no dose increase within 4 months prior to screening, or * Combination of (1) corticosteroids with no dose increase within 4 weeks prior to screening and (2) one allowed non-steroidal IST with continuous use for at least 6 months prior to screening and no dose increase within 4 months prior to screening. * Participants may enter the study on a stable dose of acetylcholinesterase inhibitors (pyridostigmine dose). The acetylcholinesterase inhibitor dose must have been stable for at least 2 weeks prior to enrollment. * Vital signs and laboratory parameters within the normal ranges at screening, or, if outside normal ranges, deemed not clinically significant by the investigator.
Exclusion criteria
* Employees of the Sponsor, contract research organization (CRO), site staff, and their family members. * Thymectomy within 12 months prior to baseline (Day 1) visit or planned thymectomy during the duration of the treatment period. * Unresected thymoma- Participants with benign thymoma resected \> 12 months prior to screening may enroll. * History of recurrent significant infections. * Known immunodeficiency disorder, including current infection or positive test for human immunodeficiency virus (HIV). * Positive test for chronic hepatitis B infection at screening. * History of untreated hepatitis C infection, or positive antibody test for hepatitis C virus (HCV). * History of active or latent tuberculosis (TB), or a positive QuantiFERON®-TB Gold test at screening, unless treatment for TB was completed per local guidelines. * History of progressive multifocal leukoencephalopathy. * Participants diagnosed with congenital myasthenic syndromes. * Receipt of any biologic B-cell-depleting therapy (eg, rituximab, ocrelizumab, obinutuzumab, ofatumumab, inebilizumab) or any experimental B-cell-depleting agent in the 6 months prior to screening. * Receipt of any other monoclonal antibody (mAb) or large molecule biologic, including but not limited to FcRn inhibitors, anti-TNF mAbs, anti-janus kinase (JAK) Stat mAbs, and complement inhibitors within 6 months prior to screening. * Receipt of the following medications or treatments at any time prior to randomization: alemtuzumab, total lymphoid irradiation, bone marrow transplant, T-cell vaccination therapy, natalizumab. * Participants who are pregnant or breastfeeding or planning to get pregnant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Clearance (CL) of Inebilizumab | Up to Week 52 |
| Volume of Distribution at Steady State (Vss) of Inebilizumab | Up to Week 52 |
| Change from Baseline in Cluster of Differentiation 20 (CD20)+ B-cell Counts | Baseline and Week 78 |
| Number of Participants Experiencing Treatment-emergent Adverse Events | Up to Week 78 |
| Number of Participants Experiencing Clinically Significant Changes in Laboratory Parameters | Up to Week 78 |
| Number of Participants Experiencing Clinically Significant Changes in Vital Signs | Up to Week 78 |
| Maximum Observed Concentration (Cmax) of Inebilizumab | Up to Week 52 |
| Area Under the Concentration-time Curve (AUC) of Inebilizumab | Up to Week 52 |
| Half-life (t1/2) of Inebilizumab | Up to Week 52 |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants with Anti-drug Antibodies (ADAs) Present | Up to Week 78 |
| Change from Baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Baseline and Week 78 |
| Change from Baseline in Euro Quality of Life-5 Dimension Youth (EQ-5D-Y) Score | Baseline and Week 78 |
| Change from Baseline in Neurological Quality of Life (Neuro-QoL) Paediatric Fatigue Score | Baseline and Week 78 |
| Change from Baseline in Quantitative Myasthenia Gravis (QMG) Score | Baseline and Week 78 |
Countries
United States
Contacts
CONTACTAmgen Call Center
STUDY_DIRECTORMD
Amgen
Outcome results
None listed