Study of Inebilizumab in Pediatric Subjects With Neuromyelitis Optica Spectrum Disorder
- Registration Number
- NCT05549258
- Lead Sponsor
- Amgen
- Brief Summary
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
Approximately 15 participants 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.
Acquired from Horizon in 2023.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 15
- Male or female participants, minimum body weight of 15 kg, 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.
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Any condition that, in the opinion of the Investigator, would interfere with the evaluation or administration of the Investigational Product or interpretation of participant safety or study results.
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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.
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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).
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B-cell counts < one-half of the lower limit of normal (LLN) for age according to the central laboratory.
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Receipt of the following at any time prior to Day 1:
- Alemtuzumab
- Total lymphoid irradiation
- Bone marrow transplant
- T-cell vaccination therapy
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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.
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Receipt of intravenous immunoglobulin (IVIG) within one month prior to Day 1.
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Receipt of any of the following within 2 months prior to Day 1:
- Cyclosporine
- Methotrexate
- Mitoxantrone
- Cyclophosphamide
- Tocilizumab
- Satralizumab
- Eculizumab
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Receipt of natalizumab (Tysabri®) within 6 months prior to Day 1.
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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).
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Diagnosed with a concurrent autoimmune disease that is uncontrolled (unless approved by the medical monitor).
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Recent receipt of live/attenuated vaccine or blood transfusion.
Receipt of any of the following:
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Any live or attenuated vaccine within 4 weeks prior to Day 1 (administration of killed vaccines and nucleoside-modified mRNA-based vaccines is acceptable; the Sponsor recommends that Investigators ensure all participants are up to date on required vaccinations prior to study entry).
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Bacillus Calmette Guérin vaccine within one year of screening.
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Blood transfusion within 4 weeks prior to screening or during screening.
- Clinically significant serious active or chronic viral, bacterial, or fungal infection that requires treatment with anti-infectives, hospitalization, or, in the Investigator's opinion, represents an additional risk to the participant, within 2 months prior to Day 1.
- Known history of congenital or acquired immunodeficiency (e.g., due to human immunodeficiency virus [HIV] infection, splenectomy, immunosuppression-related or idiopathic T-cell deficiencies) that predisposes the participant to infection.
- Positive test for chronic hepatitis B infection at screening, defined as either:
a. Positive hepatitis B surface antigen (HBsAg), or b. Positive hepatitis B core (HBc) antibody (anti-HBc) plus negative hepatitis B surface (HBs) antibody (anti-HBs).
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Positive test for hepatitis C virus antibody.
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Negative test for varicella zoster virus (VZV)-IgG.
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History of cancer, apart from squamous cell or basal cell carcinoma of the skin treated with documented success of curative therapy > 3 months prior to Day 1.
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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. Participants with latent TB or a positive QuantiFERON®-TB Gold test who are actively on anti-TB treatment can enroll if they have completed at least one month of anti-TB treatment and intend to complete the full course of anti-TB treatment. Participants with an indeterminate QuantiFERON®-TB Gold test result can enroll if a repeat QuantiFERON®-TB Gold test is negative or a tuberculin skin test is negative.
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For participants who may undergo MRI scans:
- Unable to undergo an MRI scan (e.g., hypersensitivity to Gd-containing MRI contrast agents, implanted pacemakers, defibrillators, or other metallic objects on or inside the body that limit performing MRI scans), or
- Unable to tolerate or comply with the MRI procedure.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Inebilizumab Inebilizumab Infusion of Inebilizumab
- Primary Outcome Measures
Name Time Method 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 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 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 Week 1, Week 2, Week 28, Week 80 Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs) Day 1 to Week 80 Change from Baseline in Serum Chemistry Week 1, Week 2, Week 28, Week 80 Change from Baseline in Hematology Week 1, Week 2, Week 28, Week 80 Change from Baseline in Serum Immunoglobulins Week 1, Week 2, Week 28, Week 80 Change from Baseline in Systolic Blood Pressure Week 1, Week 2, Week 28, Week 80 Change from Baseline in Diastolic Blood Pressure Week 1, Week 2, Week 28, Week 80 Change from Baseline in Pulse Rate Week 1, Week 2, Week 28, Week 80 Change from Baseline in Respiratory Rate Week 1, Week 2, Week 28, Week 80 Change from Baseline in Body Temperature Week 1, Week 2, Week 28, Week 80
- Secondary Outcome Measures
Name Time Method Change From Baseline in Expanded Disability Status Scale Day 1 to Week 80 Change in baseline comprised from results of 8 Functional Systems: Visual, Brainstem, Pryamidal, Cerebellar, Sensory, Bowel, Bladder, and Cerebral. A higher score indicates a higher grade of impairment and disability.
Anti-drug antibody (ADA) rate Day 1 to Week 80 Disease Activity: Time to First Relapse Day 1 to Week 80 Disease Activity: Proportion of Relapse-free Participants 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 Day 1 to Week 80 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.
HRQoL change from baseline in Pediatric Quality of Life Inventory Day 1 to Week 80 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.
Visual Acuity change from baseline Day 1 to Week 80
Trial Locations
- Locations (17)
Great Ormond Street Hospital
🇬🇧London, London, City Of, United Kingdom
Loma Linda University Children's Hospital
🇺🇸Loma Linda, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Hospital de Pediatría S.A.M.I.C.- Prof. Dr. Juan P. Garrahan
🇦🇷Parque Patricios, Ciudad Autónoma De BuenosAires, Argentina
Hospital Santa Izabel-Rua Floriano Peixoto 300
🇧🇷Salvador, Bahia, Brazil
Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)
🇧🇷Porto Alegre/RS, Brazil
CPQuali Pesquisa Clínica Sao Paulo
🇧🇷São Paulo, Brazil
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
🇧🇷São Paulo, Brazil
Hospital For Sick Children
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier Universitaire de Bicêtre
🇫🇷Le Kremlin-Bicêtre, Val-de-Marne, France
Erasmus MC Sophia Children's Hospital-Wytemaweg 80
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Uniwersyteckie Centrum Kliniczne w Gdansku - Smoluchowskiego 17
🇵🇱Gdańsk, Poland
Clinic for Neurology and Psychiatry for Children and Youth
🇷🇸Beograd, Belgrade, Serbia
Hospital Sant Joan de Deu - PIN
🇪🇸Espluges De Llobregat, Barcelona, Spain
Karolinska Universitetssjukhuset Solna
🇸🇪Stockholm, Stockholms Lan, Sweden
Evelina London Children's Hospital
🇬🇧London, London, City Of, United Kingdom
Birmingham Women's and Children's NHS Foundation Trust
🇬🇧Birmingham, West Midlands, United Kingdom