Efficacy and Safety Study of Ravulizumab IV in Pediatric Participants With NMOSD

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the safety and efficacy of ravulizumab in pediatric participants with Neuromyelitis Optica Spectrum Disorder (NMOSD).

Official Title
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A Phase 2/3, Open-label, Historical-controlled, Single-arm, Multicenter Study to Evaluate the Efficacy, Pharmacokinetics, Pharmacodynamics, and Safety of Ravulizumab in Children and Adolescents With Aquaporin-4 Antibody Positive (AQP4-Ab [+]) Neuromyelitis Optica Spectrum Disorder (NMOSD)

Conditions
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Neuromyelitis Optica Spectrum Disorder

Intervention / Treatment
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* Drug: Ravulizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be anti-AQP4 Ab-positive and have a diagnosis of NMOSD as defined by the 2015 international consensus diagnostic criteria. Complement inhibitor treatment-naïve participants must have had at least 1 attack or relapse in the last 12 months prior to the Screening Period. Expanded Disability Status Scale (EDSS) score ≤ 7. Eculizumab-experienced participants must be clinically stable per Investigator for 30 days and have been treated with eculizumab in Study ECU-NMO-303 for at least 90 days prior to screening with no missed doses within 2 months prior to Day 1. Participants who enter the study receiving supportive IST(s) (eg, corticosteroid, azathioprine [AZA], mycophenolate mofetil [MMF], methotrexate [MTX], tacrolimus [TAC], cyclosporin [CsA], or cyclophosphamide [CYC]) for the prevention of relapse, either in combination or monotherapy, must be on a stable dosing regimen of adequate duration prior to Screening and remain on a stable dosing regimen during the Screening Period. To reduce the risk of meningococcal infection (Neisseria meningitidis), all participants must be vaccinated against meningococcal infection. Documented vaccination for Hib and S pneumoniae at least 14 days prior to Day 1 according to national/local guidelines for the applicable age group. Exclusion Criteria: Use of rituximab within 6 months prior to Day 1. Currently treated with a biologic medications (other than eculizumab) that may affect immune system functioning, or has stopped treatment with a biologic medication that may affect immune system functioning, and 5 half lives of the medication have not elapsed by the time of the Screening Visit. Use of intravenous immunoglobulin (IVIg) or plasma exchange (PE) within 3 weeks prior to Screening. Participation in another investigational drug or investigational device study (other than Study ECU-NMO-303) within 5 half lives of that investigational product (if known) or 30 days before initiation of the first dose of study drug, whichever is longer. Use of immunomodulatory therapies for multiple sclerosis within 3 months prior to Screening.

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: Ravulizumab<br>During the Primary Treatment Period, all participants will receive weight-based dosing of ravulizumab IV for a total of 50 weeks of treatment. During the Extension Period, participants will continue to receive weight-based dosing of ravulizumab IV for up to 104 weeks. | Drug: Ravulizumab<br>* Participants will receive a weight-based loading dose of ravulizumab on Day 1, followed by weight-based maintenance treatment with ravulizumab on Day 15 and every 8 weeks (q8w) after or once every 4 weeks (q4w) depending on weight. During the Extension Period, participants will continue to receive weight-based maintenance doses of ravulizumab IV on Day 351 and q8w or q4w, depending on weight.<br>* Other names: Ultomiris;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Annualized Relapse Rate at Week 50 |  | Baseline, Week 50 | 
| Time to First Adjudicated On-trial Relapse through Week 50 |  | Baseline through Week 50 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Expanded Disability Status Scale Score At Week 50 | The score ranges are 0 to 10, higher score indicates worse outcome. | Baseline, Week 50 | 
| Change From Baseline in Hauser Ambulation Index at Week 50 | The score ranges are 0 to 9, higher score indicates worse outcome. | Baseline, Week 50 | 
| Change From Baseline in Visual Acuity at Week 50 |  | Baseline, Week 50 | 
| Change From Baseline in Confrontational Visual Fields at Week 50 |  | Baseline, Week 50 | 
| Change From Baseline in Color Vision at Week 50 |  | Baseline, Week 50 | 
| Serum Ravulizumab Concentration |  | Predose and postdose (at end of infusion) on Day 1, Weeks 2, 10, 18, 26, and 42, and predose on Week 50 | 
| Change from Baseline in Free Serum Complement Component 5 (C5) Concentration Over Time Through Week 50 |  | Baseline through Week 50 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ravulizumab, NMO, ALXN1210, Neuromyelitis Optica Spectrum Disorder, CNS Autoimmune Disorders, NMOSD