Clinical trial NCT05549258: Study of Inebilizumab in Pediatric Subjects With Neuromyelitis Optica Spectrum Disorder
Official title: An Open-Label Multicenter Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Inebilizumab in Pediatric Subjects With Neuromyelitis Optica Spectrum Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Neuromyelitis Optica Spectrum Disorder
Keywords: NMOSD
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2022-09-22
Enrollment: 15
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

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 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:

  1. Alemtuzumab
  2. Total lymphoid irradiation
  3. Bone marrow transplant
  4. 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:

  1. Cyclosporine
  2. Methotrexate
  3. Mitoxantrone
  4. Cyclophosphamide
  5. Tocilizumab
  6. Satralizumab
  7. 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:

1. 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).
2. Bacillus Calmette Guérin vaccine within one year of screening.
3. 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:

  1. 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
  2. Unable to tolerate or comply with the MRI procedure.

Primary outcomes:
measure: Maximum Observed Concentration (Cmax) of Inebilizumab
timeFrame: Day 1 to Week 28
measure: Area Under the Concentration Versus Time Curve of Inebilizumab from Time 0 to 14 Days Post-dose (AUC0-14d)
timeFrame: Day 1 to pre-dose on Day 15
measure: Area Under the Concentration Versus Time Curve of Inebilizumab from Time 0 Extrapolated to Infinity (AUC0-Inf)
timeFrame: Day 1 to Week 80
measure: Systemic Clearance (CL) of Inebilizumab
timeFrame: Day 1 to Week 80
measure: Terminal Elimination Half-life (t½) of Inebilizumab
timeFrame: Day 1 to Week 80
measure: Volume of Distribution at Steady State (VSS) of Inebilizumab
timeFrame: Day 1 to Week 80
measure: Change from Baseline in Peripheral Cluster of Differentiation (CD)20-positive B-cell Counts
timeFrame: Week 1, Week 2, Week 28, Week 80
measure: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)
timeFrame: Day 1 to Week 80
measure: Change from Baseline in Serum Chemistry
timeFrame: Week 1, Week 2, Week 28, Week 80
measure: Change from Baseline in Hematology
timeFrame: Week 1, Week 2, Week 28, Week 80
measure: Change from Baseline in Serum Immunoglobulins
timeFrame: Week 1, Week 2, Week 28, Week 80
measure: Change from Baseline in Systolic Blood Pressure
timeFrame: Week 1, Week 2, Week 28, Week 80
measure: Change from Baseline in Diastolic Blood Pressure
timeFrame: Week 1, Week 2, Week 28, Week 80
measure: Change from Baseline in Pulse Rate
timeFrame: Week 1, Week 2, Week 28, Week 80
measure: Change from Baseline in Respiratory Rate
timeFrame: Week 1, Week 2, Week 28, Week 80
measure: Change from Baseline in Body Temperature
timeFrame: Week 1, Week 2, Week 28, Week 80
Secondary outcomes:
measure: Disease Activity: Time to First Relapse
timeFrame: Day 1 to Week 80
measure: Disease Activity: Proportion of Relapse-free Participants
timeFrame: Day 1 to Week 80
measure: Disease Activity: Annualized Relapse Rate
timeFrame: Day 1 to Week 80
measure: Health-Related Quality of Life (HRQoL) change from baseline in Euro Quality of Life-5 Dimension Youth score
timeFrame: Day 1 to Week 80
measure: HRQoL change from baseline in Pediatric Quality of Life Inventory
timeFrame: Day 1 to Week 80
measure: Visual Acuity change from baseline
timeFrame: Day 1 to Week 80
measure: Change From Baseline in Expanded Disability Status Scale
timeFrame: Day 1 to Week 80
measure: Anti-drug antibody (ADA) rate
timeFrame: Day 1 to Week 80
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCSD Altman Clinical and Translational Research Institute Building
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Children's Hospital
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Parque Patricios
country: Argentina
facility: Hospital de Pediatría S.A.M.I.C.- Prof. Dr. Juan P. Garrahan
state: Ciudad Autónoma De BuenosAires
city: Salvador
country: Brazil
facility: Hospital Santa Izabel-Rua Floriano Peixoto 300
state: Bahia
city: Porto Alegre/RS
country: Brazil
facility: Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)
city: São Paulo
country: Brazil
facility: CPQuali Pesquisa Clínica Sao Paulo
city: São Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
city: Toronto
country: Canada
facility: Hospital For Sick Children
state: Ontario
city: Le Kremlin-Bicêtre
country: France
facility: Centre Hospitalier Universitaire de Bicêtre
state: Val-de-Marne
city: Rotterdam
country: Netherlands
facility: Erasmus MC Sophia Children's Hospital-Wytemaweg 80
state: Zuid-Holland
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne w Gdansku - Smoluchowskiego 17
city: Beograd
country: Serbia
facility: Clinic for Neurology and Psychiatry for Children and Youth
state: Belgrade
city: Espluges De Llobregat
country: Spain
facility: Hospital Sant Joan de Deu - PIN
state: Barcelona
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Solna
state: Stockholms Lan
city: London
country: United Kingdom
facility: Evelina London Children's Hospital
state: London, City Of
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
state: London, City Of
city: Birmingham
country: United Kingdom
facility: Birmingham Women's and Children's NHS Foundation Trust
state: West Midlands
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: