Clinical trial NCT06987539: A Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Inebilizumab in Children With Generalized Myasthenia Gravis (gMG)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Generalized Myasthenia Gravis
Keywords: Generalized Myasthenia Gravis
Inebilizumab
AMG 335
Uplizna
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2025-05-23
Enrollment: 15
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.
* 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 may enter the study 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

* 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.
* 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.
* Participants who are pregnant or breastfeeding or planning to get pregnant.

Primary outcomes:
measure: Maximum Observed Concentration (Cmax) of Inebilizumab
timeFrame: Up to Week 52
measure: Area Under the Concentration-time Curve (AUC) of Inebilizumab
timeFrame: Up to Week 52
measure: Half-life (t1/2) of Inebilizumab
timeFrame: Up to Week 52
measure: Clearance (CL) of Inebilizumab
timeFrame: Up to Week 52
measure: Volume of Distribution at Steady State (Vss) of Inebilizumab
timeFrame: Up to Week 52
measure: Change from Baseline in Cluster of Differentiation 20 (CD20)+ B-cell Counts
timeFrame: Baseline and Week 78
measure: Number of Participants Experiencing Treatment-emergent Adverse Events
timeFrame: Up to Week 78
measure: Number of Participants Experiencing Clinically Significant Changes in Laboratory Parameters
timeFrame: Up to Week 78
measure: Number of Participants Experiencing Clinically Significant Changes in Vital Signs
timeFrame: Up to Week 78
Secondary outcomes:
measure: Change from Baseline in Quantitative Myasthenia Gravis (QMG) Score
timeFrame: Baseline and Week 78
measure: Change from Baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) Score
timeFrame: Baseline and Week 78
measure: Change from Baseline in Euro Quality of Life-5 Dimension Youth (EQ-5D-Y) Score
timeFrame: Baseline and Week 78
measure: Change from Baseline in Neurological Quality of Life (Neuro-QoL) Paediatric Fatigue Score
timeFrame: Baseline and Week 78
measure: Change from Baseline in Patient Global Impression of Severity (PGI-S) Score
timeFrame: Baseline and Week 78
measure: Change from Baseline in Patient Global Impression of Change (PGI-C) Score
timeFrame: Baseline and Week 78
measure: Change from Baseline in Myasthenia Gravis Quality of Life-15 (MG-QOL15) Score
timeFrame: Baseline and Week 78
measure: Number of Participants with Anti-drug Antibodies (ADAs) Present
timeFrame: Up to Week 78
measure: Hepatitis B Vaccine Antibody (IgG) Titers
timeFrame: Up to Week 78
measure: Hemophilus Influenza Type B Vaccine Antibody (IgG) Titers
timeFrame: Up to Week 78
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: