Study of Inebilizumab in Pediatric Subjects With Neuromyelitis Optica Spectrum Disorder

Study Overview
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Brief Summary
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A Phase 2, open-label, multicenter study to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of inebilizumab in eligible pediatric participants 2 to < 18 years of age with recently active neuromyelitis optica spectrum disorder (NMOSD) who are seropositive for autoantibodies against aquaporin-4 (AQP4-immunoglobulin [Ig]G).

Detailed Description
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Approximately 15 subjects to be enrolled and receive Inebilizumab administered intravenously over 28 weeks. The maximum trial duration per participant is approximately 80 weeks, including up to 4 week screening period, 9 visits during a 28 week open-label treatment period, and approximately 4 visits during a 52 week follow-up period. Safety evaluations will be performed regularly throughout the course of the study.

Official Title
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An Open-Label Multicenter Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Inebilizumab in Pediatric Subjects With Neuromyelitis Optica Spectrum Disorder

Conditions
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Neuromyelitis Optica Spectrum Disorder

Intervention / Treatment
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* Drug: Inebilizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects age 2 to < 18 years at the time of screening. Positive serum anti-AQP4-IgG result at screening and diagnosed with NMOSD according to the criteria of Wingerchuk et al, 2015. Documented history of one or more NMOSD acute relapses within the last year, or 2 or more NMOSD acute relapses within 2 years prior to screening. Exclusion Criteria: Any condition that, in the opinion of the Investigator, would interfere with the evaluation or administration of the Investigational Product or interpretation of subject safety or study results Concurrent/previous enrollment in another clinical study involving an investigational treatment within 4 weeks or 5 published half-lives of the investigational treatment, whichever is the longer, prior to Day 1 Evidence of significant hepatic, renal, or metabolic dysfunction or significant hematological abnormality (one repeat test may be conducted to confirm results within the same screening period): B-cell counts < one-half of the lower limit of normal (LLN) for age according to the central laboratory Receipt of the following at any time prior to Day 1: Alemtuzumab Total lymphoid irradiation Bone marrow transplant T-cell vaccination therapy Receipt of rituximab or any experimental B-cell depleting agent within 6 months prior to screening unless B-cell counts have returned to ≥ one-half the LLN Receipt of intravenous immunoglobulin (IVIG) within one month prior to Day 1 Receipt of any of the following within 2 months prior to Day 1: Cyclosporine Methotrexate Mitoxantrone Cyclophosphamide Tocilizumab Satralizumab Eculizumab Receipt of natalizumab (Tysabri®) within 6 months prior to Day 1 Severe drug allergic history or anaphylaxis to 2 or more food products or medicine (including known sensitivity to acetaminophen/paracetamol, diphenhydramine or equivalent antihistamine, and methylprednisolone or equivalent glucocorticoid) Diagnosed with a concurrent autoimmune disease that is uncontrolled (unless approved by the medical monitor) Recent receipt of live/attenuated vaccine or blood transfusion

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inebilizumab<br>Infusion of Inebilizumab | Drug: Inebilizumab<br>* Inebilizumab administered intravenously (IV) over a total of 28 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration (Cmax) of inebilizumab |  | Day 1 to Week 28 | 
| Area Under the Concentration Versus Time Curve of inebilizumab from Time 0 to 14 days post-dose (AUC0-14d) |  | Day 1 to pre-dose on Day 15 | 
| Area Under the Concentration Versus Time Curve of inebilizumab from Time 0 extrapolated to infinity (AUC0-Inf) |  | Day 1 to Week 80 | 
| Systemic Clearance (CL) of inebilizumab |  | Day 1 to Week 80 | 
| Terminal Elimination Half-life (t½) of inebilizumab |  | Day 1 to Week 80 | 
| Volume of Distribution at Steady State (VSS) of inebilizumab |  | Day 1 to Week 80 | 
| Change from Baseline in Peripheral Cluster of Differentiation (CD)20-positive B-cell counts |  | Baseline, Week 1, Week 2, Week 28, Week 80 | 
| Number of subjects with of treatment-emergent events (adverse events (TEAEs), serious adverse events (TESAEs), and adverse events of special interest (AESIs)). |  | Day 1 to Week 80 | 
| Change from Baseline in Serum Chemistry |  | Baseline, Week 1, Week 2, Week 28, Week 80 | 
| Change from Baseline in Hematology |  | Baseline, Week 1, Week 2, Week 28, Week 80 | 
| Change from Baseline in Serum Immunoglobulins |  | Baseline, Week 1, Week 2, Week 28, Week 80 | 
| Change from Baseline in Systolic Blood Pressure |  | Baseline, Week 1, Week 2, Week 28, Week 80 | 
| Change from Baseline in Diastolic Blood Pressure |  | Baseline, Week 1, Week 2, Week 28, Week 80 | 
| Change from Baseline in Pulse Rate |  | Baseline, Week 1, Week 2, Week 28, Week 80 | 
| Change from Baseline in Respiratory Rate |  | Baseline, Week 1, Week 2, Week 28, Week 80 | 
| Change from Baseline in Body Temperature |  | Baseline, Week 1, Week 2, Week 28, Week 80 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Activity: Time to first relapse. |  | Day 1 to Week 80 | 
| Disease Activity: Proportion of relapse-free subjects. |  | Day 1 to Week 80 | 
| Disease Activity: Annualized relapse rate. |  | Day 1 to Week 80 | 
| Health-Related Quality of Life (HRQoL) change from baseline in Euro Quality of Life-5 Dimension Youth score. | Change in baseline for the 5 dimensions: mobility, looking after myself, doing usual activities, having pain or discomfort, and feeling worried, sad, or unhappy. A higher score indicates onset or worsening of an affective disorder. | Day 1 to Week 80 | 
| Health-Related Quality of Life (HRQoL) change from baseline in Pediatric Quality of Life Inventory. | Change in baseline comprised from 4 generic core scales: Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning. A higher score indicates a better quality of life. | Day 1 to Week 80 | 
| Visual Acuity change from baseline. |  | Day 1 to Week 80 | 
| Expanded Disability Status Scale change from baseline. | Change in baseline comprised from results of 7 Functional Systems: Visual, Brainstem, Pryamidal, Cerebellar, Sensory, Bowel, Bladder, and Cerebral. A higher score indicates a higher grade of impairment and disability. | Day 1 to Week 80 | 
| Anti-drug antibody (ADA) rate. |  | Day 1 to Week 80 |