Phase 2 Study of the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Inebilizumab in Pediatric Patients with Generalized Myasthenia Gravis

Trial ID: 2025-520993-20-00
Protocol: 20240236
Sponsor: Amgen Inc.

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Diseases & Conditions

Myasthenia gravis

Objectives

The primary objectives are to characterize the pharmacokinetics, pharmacodynamics, safety, and tolerability of inebilizumab in pediatric patients with generalized Myasthenia Gravis.

Assessment of disease activity.
Evaluation of quality of life and disability related to the condition.
Characterization of immunogenicity.

Participants

This study involves 8 participants diagnosed with generalized Myasthenia Gravis. The study population consists of pediatric patients, including both males and females, aged between 2 and 18 years. Eligible subjects must have a Myasthenia Gravis Foundation of America Clinical Classification of Class II, III, or IV and a Quantitative Myasthenia Gravis score of 11 or greater at screening. Diagnosis requires positive serologic testing for anti-AChR or anti-MuSK antibodies along with specific neuromuscular transmission test results or clinical indicators. Participants may be receiving stable doses of corticosteroids, specific non-steroidal immunosuppressive therapies, or acetylcholinesterase inhibitors. The objectives are:

To characterize the pharmacokinetics of inebilizumab.
To characterize the pharmacodynamics of inebilizumab.
To assess the safety and tolerability of inebilizumab.

Plans and Procedures

This Phase 2, open-label, multicenter study is designed to evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of inebilizumab in pediatric patients aged 2 to less than 18 years diagnosed with generalized Myasthenia Gravis. The research methodology focuses on characterizing the drug's profile through the assessment of parameters such as maximum observed concentration, area under the concentration-time curve, half-life, clearance, and volume of distribution at steady state. Additionally, the study monitors changes in CD20+ B-cell counts, treatment-emergent adverse events, and laboratory parameters. The clinical sequence begins with a screening visit to confirm diagnosis via anti-AChR or anti-MuSK antibody titers and to ensure adherence to specific immunosuppressive therapies and acetylcholinesterase inhibitor stability requirements. Following screening, participants undergo treatment and subsequent follow-up assessments to evaluate efficacy through the Quantitative Myasthenia Gravis score and Myasthenia Gravis Activities of Daily Living score. The trial is estimated to conclude by March 2030.

Treatment

The investigational medicinal product is inebilizumab, provided as Uplizna 100 mg concentrate for solution for infusion. The administration is performed via intravenous use.

Efficacy

The efficacy and pharmacological profile of inebilizumab in pediatric participants with generalized myasthenia gravis will be evaluated through specific primary and secondary endpoints. Primary assessments include the determination of pharmacokinetic parameters, specifically maximum observed concentration (Cmax), area under the concentration-time curve (AUC), half-life (t1/2), clearance (CL), and volume of distribution at steady state (Vss). Additionally, the change from baseline in cluster of differentiation 20 (CD20)+ B-cell counts will be measured.

Secondary efficacy assessments involve the evaluation of clinical outcomes using the Quantitative Myasthenia Gravis (QMG) score and the Myasthenia Gravis Activities of Daily Living (MG-ADL) score. The presence of anti-drug antibodies (ADAs) will also be monitored during the study.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Age ≥ 2 to < 18 years of age on the day of enrollment.
"Diagnosis of gMG defined as: Positive serologic test for anti-AChR or anti-MuSK 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 may enter the study on: (1) Corticosteroids only, with no dose increase within 4 weeks prior to screening, or (2) 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."

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Exclusion Criteria

Thymectomy within 12 months prior to baseline (day 1) visit or planned thymectomy during the duration of the treatment period.
"Unresected thymoma. Note: Participants with benign thymoma resected > 12 months prior to screening may enroll. Benign is defined as no known metastases and no extension into or beyond the capsule on pathological examination. Imaging to evaluate for thymoma must have been performed prior to screening per standard of care."
Hospitalization for any reason < 30 days prior to screening.
Current or recent gMG exacerbation that has not returned to baseline/resolved within at least 30 days prior to screening.
History of recurrent significant infections (eg, requiring hospitalization or IV antibiotics).
"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 mAb or large molecule biologic, including but not limited to FcRn inhibitors, anti-TNF mAbs, anti-JAK Stat mAbs, and complement inhibitors within 6 months prior to screening."
"Receipt within the 4 weeks prior to screening: a) Live attenuated vaccine (administration of inactivated [killed] vaccine is acceptable); b) Blood transfusion"
"Participants of childbearing potential unwilling to use protocol-specified method of contraception see (Section 11.5) during treatment and for an additional 6 months after the last dose of investigational product."
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