A Study To Evaluate Pharmacokinetics, Efficacy, Safety, Tolerability, And Pharmacodynamics Of Satralizumab In Pediatric Patients With Aquaporin-4 Antibody Positive Neuromyelitis Optica Spectrum Disorder (NMOSD)

Study Overview
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Brief Summary
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This study will primarily evaluate the pharmacokinetics of satralizumab in pediatric patients aged 2-11 years with anti-aquaporin-4 (AQP4) antibody seropositive neuromyelitis optica spectrum disorder (NMOSD). Efficacy, safety, tolerability, and pharmacodynamics will be evaluated in a descriptive manner, given the small number of patients who will be enrolled in this study.

Official Title
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A Phase III, Multicenter, Open-Label, Uncontrolled Study To Evaluate Pharmacokinetics, Efficacy, Safety, Tolerability, And Pharmacodynamics Of Satralizumab In Pediatric Patients With AQP4 Antibody Positive Neuromyelitis Optica Spectrum Disorder (NMOSD)

Conditions
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Neuromyelitis Optica Spectrum Disorder, NMOSD

Intervention / Treatment
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* Drug: Satralizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age at screening 2-11 years, inclusive Body weight at screening >=10 kg For female patients of childbearing potential (postmenarchal): agreement to either remain completely abstinent (refrain from heterosexual intercourse) or to use a reliable means of contraception Diagnosed as having NMOSD with AQP4 antibody seropositive status as defined by the Wingerchuk 2015 criteria Clinical evidence of at least one documented attack (including first attack) in the last year prior to screening Neurological stability for >=30 days prior to both screening and baseline Expanded Disability Status Scale (EDSS) 0 to 6.5 For patients receiving a baseline immunosuppressant treatment and planning to continue on these therapies, treatment must be at stable dose for 4 weeks prior to baseline Exclusion Criteria: Pregnancy or lactation Evidence of other demyelinating disease mimicking NMOSD Active or presence of recurrent bacterial, viral, fungal, mycobacterial infection, or other infection at baseline Evidence of chronic active hepatitis B or C Evidence of untreated latent or active tuberculosis (TB) Receipt of a live or live-attenuated vaccine within 6 weeks prior to baseline History of severe allergic reaction to a biologic agent

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 11 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Participants with body weight ≥10kg to <20kg<br>Satralizumab will be administered SC Q6W in a cohort of at least 2 evaluable patients | Drug: Satralizumab<br>* Participants will receive satralizumab treatment for a minimum of 48 weeks and then will have the opportunity to enter an optional satralizumab extension (OSE) period.<br>|
| Experimental: Cohort 2 Participants with body weight ≥20kg to <40kg<br>Satralizumab will be administered SC at Weeks 0, 2, 4, and Q4W thereafter. | Drug: Satralizumab<br>* Participants will receive satralizumab treatment for a minimum of 48 weeks and then will have the opportunity to enter an optional satralizumab extension (OSE) period.<br>|
| Experimental: Cohort 3 Participants with body weight ≥40kg<br>Satralizumab will be administered SC at Weeks 0, 2, 4, and Q4W thereafter. | Drug: Satralizumab<br>* Participants will receive satralizumab treatment for a minimum of 48 weeks and then will have the opportunity to enter an optional satralizumab extension (OSE) period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of observed serum concentration [Cthrough] of satralizumab |  | Week 48 | 
| Apparent clearance [CL/F] of satralizumab |  | Week 48 | 
| Apparent volume of distribution [V/F] of satralizumab |  | Week 48 | 
| Area under the concentration-time curve [AUC] of satralizumab |  | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of relapse-free patients by Week 48 |  | Week 48 | 
| Annualized relapse rate (ARR), defined as the average number of relapses for each year of the study |  | Week 48 | 
| Time to first relapse (TFR) after randomization, defined as the time from randomization until the first occurrence of relapse, as determined by the investigator |  | Week 48 | 
| Time to relapse requiring rescue therapy |  | Week 48 | 
| Change from baseline in Expanded Disability Status Scale (EDSS) at Weeks 24 and 48 |  | Baseline, Week 24, Week 48 | 
| Change from baseline in visual acuity at Weeks 24 and 48 |  | Baseline, Week 24, Week 48 | 
| Change from baseline in FACES Pain Rating Scale at Weeks 24 and 48 |  | Baseline, Week 24, Week 48 | 
| Change from baseline in EuroQol 5-Dimension, Youth (EQ-5D-Y) score and its proxy at Weeks 24 and 48 |  | Baseline, Week 24, Week 48 | 
| Incidence and severity of adverse events |  | Week 48 |