Study of Inebilizumab in Pediatric Subjects With Neuromyelitis Optica Spectrum Disorder

Официальное название

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

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат Inebilizumab
  Inebilizumab administered intravenously (IV) over a total of 28 weeks.

Первичные конечные точки

• Maximum Observed Concentration (Cmax) of Inebilizumab [Срок оценки: Day 1 to Week 28]
• Area Under the Concentration Versus Time Curve of Inebilizumab from Time 0 to 14 Days Post-dose (AUC0-14d) [Срок оценки: 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) [Срок оценки: Day 1 to Week 80]
• Systemic Clearance (CL) of Inebilizumab [Срок оценки: Day 1 to Week 80]
• Terminal Elimination Half-life (t½) of Inebilizumab [Срок оценки: Day 1 to Week 80]
• Volume of Distribution at Steady State (VSS) of Inebilizumab [Срок оценки: Day 1 to Week 80]
• Change from Baseline in Peripheral Cluster of Differentiation (CD)20-positive B-cell Counts [Срок оценки: 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) [Срок оценки: Day 1 to Week 80]
• Change from Baseline in Serum Chemistry [Срок оценки: Week 1, Week 2, Week 28, Week 80]
• Change from Baseline in Hematology [Срок оценки: Week 1, Week 2, Week 28, Week 80]

Вторичные конечные точки (8)

• Disease Activity: Time to First Relapse [Срок оценки: Day 1 to Week 80]
• Disease Activity: Proportion of Relapse-free Participants [Срок оценки: Day 1 to Week 80]
• Disease Activity: Annualized Relapse Rate [Срок оценки: Day 1 to Week 80]
• Health-Related Quality of Life (HRQoL) change from baseline in Euro Quality of Life-5 Dimension Youth score [Срок оценки: Day 1 to Week 80]
• HRQoL change from baseline in Pediatric Quality of Life Inventory [Срок оценки: Day 1 to Week 80]
• Visual Acuity change from baseline [Срок оценки: Day 1 to Week 80]
• Change From Baseline in Expanded Disability Status Scale [Срок оценки: Day 1 to Week 80]
• Anti-drug antibody (ADA) rate [Срок оценки: Day 1 to Week 80]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.
• 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.

Receipt of any of the following:

• 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).
• Bacillus Calmette Guérin vaccine within one year of screening.
• 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).

• Positive test for hepatitis C virus antibody.
• Negative test for varicella zoster virus (VZV)-IgG.
• 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.
• 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.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 4 центра

• UCSD Altman Clinical and Translational Research Institute Building — La Jolla
• Loma Linda University Children's Hospital - PIN — Loma Linda
• Massachusetts General Hospital — Boston
• University of Texas Southwestern Medical Center — Dallas

Бразилия · 4 центра

• Hospital Santa Izabel-Rua Floriano Peixoto 300 — Salvador
• Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS) — Porto Alegre/RS
• CPQuali Pesquisa Clínica Sao Paulo — São Paulo
• Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo — São Paulo

Великобритания · 3 центра

• Evelina London Children's Hospital — London
• Great Ormond Street Hospital - PPDS — London
• Birmingham Women's and Children's NHS Foundation Trust — Birmingham

Аргентина · 1 центр

• Hospital de Pediatría S.A.M.I.C.- Prof. Dr. Juan P. Garrahan — Parque Patricios

Канада · 1 центр

• Hospital For Sick Children — Toronto

Франция · 1 центр

• Centre Hospitalier Universitaire de Bicêtre — Le Kremlin-Bicêtre

Нидерланды · 1 центр

• Erasmus MC Sophia Children's Hospital-Wytemaweg 80 — Rotterdam

Польша · 1 центр

• Uniwersyteckie Centrum Kliniczne w Gdansku - Smoluchowskiego 17 — Gdansk

Сербия · 1 центр

• Clinic for Neurology and Psychiatry for Children and Youth — Belgrade

Испания · 1 центр

• Hospital Sant Joan de Deu - PIN — Espluges de Llobregat

Швеция · 1 центр

• Karolinska Universitetssjukhuset Solna — Stockholm

Идентификаторы

NCT: NCT05549258 · VIB0551.P2.S2.NMO · 2023-510007-22

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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