A Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Inebilizumab in Children With Generalized Myasthenia Gravis (gMG)

A Phase 2 Open-label Multicenter Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Inebilizumab in Children From 2 Years to Less Than 18 Years of Age With Generalized Myasthenia Gravis (gMG)

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.

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.

• 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.

Tacrolimus is allowed in Japan only, with continued use for ≥ 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.