Neuromyelitis Optica Spectrum Disorder Inebilizumab Study in Children and Adolescents

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Horizon Therapeutics Ireland Designated Activity Company

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

20 Jul 2022 → ongoing

Decision date (initial)

2024-05-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Horizon Therapeutics Ireland DAC

External identifiers

EU CT number

2023-510007-22-00

EudraCT number

2021-003528-33

ClinicalTrials.gov

NCT05549258

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Pharmacokinetic, Pharmacodynamic

1. To characterize the PK of inebilizumab administered in pediatric subjects with NMOSD
2. To characterize the PD of inebilizumab administered in pediatric subjects with NMOSD
3. To assess the safety and tolerability of inebilizumab administered in pediatric subjects with NMOSD

Secondary objectives 1

1. 1. To assess disease activity when inebilizumab is administered in pediatric subjects with NMOSD 2. To assess health-related quality of life (HRQoL) when inebilizumab is administered in pediatric subjects with NMOSD 3. To assess visual acuity when inebilizumab is administered in pediatric subjects with NMOSD 4. To assess disability when inebilizumab is administered in pediatric subjects with NMOSD 5. To characterize the immunogenicity of inebilizumab administered in pediatric subjects with NMOSD

Conditions and MedDRA coding

Neuromyelitis optica spectrum disorder (NMOSD; also known as Devic's syndrome and previously known as neuromyelitis optica [NMO])

Study design 3 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001911-PIP01-15

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Written informed consent and any locally required data privacy authorization obtained from the subject's legally authorized representative in accordance with regional laws or regulations and the subject's assent, when applicable, prior to performing any protocolrelated procedures. 2. Male or female subjects, minimum body weight of 15 kg, age 2 to < 18 years at the time of screening. 3. Positive serum anti-AQP4-IgG result at screening (verified by the XML File Identifier: /BYZ1q6d7Yxs391VjDKysjqZIlE=Page 11/27 central laboratory) and diagnosed with NMOSD 4. 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. 5. Female subjects of childbearing potential who are sexually active with a nonsterilized male partner must agree to use a highly effective method of contraception from screening until 6 months after the final dose of investigational product (IP) 6. Nonsterilized male subjects who are sexually active with a female partner of childbearing potential must agree to use a male condom from Day 1 until 3 months after the final dose of IP.

Exclusion criteria 2

1. 1. Any condition that, in the opinion of the Investigator, would interfere with the evaluation or administration of the IP or interpretation of subject safety or study results 2. 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 3. Females who are breastfeeding, pregnant, or who intend to become pregnant at any time from screening until 6 months after the final dose of IP 4. Known history of allergy or reaction to any component of the IP formulation or history of anaphylaxis following any biologic therapy 5. Evidence of alcohol, drug, or chemical abuse, or a recent history of such abuse < 1 year prior to Day 1 6. Major surgery within 8 weeks prior to screening 7. Spontaneous or induced abortion, still or live birth, or pregnancy ≤ 4 weeks prior to screening 8. Evidence of significant hepatic, renal, or metabolic dysfunction or significant hematological abnormality 9. B-cell counts < one-half of the lower limit of normal (LLN) for age according to the central laboratory 10. Receipt of the following at any time prior to Day 1: a. Alemtuzumab b. Total lymphoid irradiation c. Bone marrow transplant d. T-cell vaccination therapy 11. 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. 12. Receipt of intravenous immunoglobulin (IVIG) within one month prior to Day 1 13. Receipt of any of the following within 2 months prior to Day 1: a. Cyclosporine b. Methotrexate c. Mitoxantrone d. Cyclophosphamide e. Tocilizumab f. Satralizumab g. Eculizumab 14. Receipt of natalizumab (Tysabri®) within 6 months prior to Day 1 15. Severe drug allergic history or anaphylaxis to 2 or more food products or medicine 16. Diagnosed with a concurrent autoimmune disease that is uncontrolled (unless approved by the medical monitor) 17. Receipt of any of the following: a. Any live or attenuated vaccine within 4 weeks prior to Day 1 b. Bacillus Calmette-Guérin vaccine within one year of screening c. Blood transfusion within 4 weeks prior to screening or during screening 18. Clinically significant serious active or chronic viral, bacterial, or fungal infection that requires treatment with anti-infectives, within 2 months prior to Day 1 19. Known history of congenital or acquired immunodeficiency that predisposes the subject to infection 20. Positive test for chronic hepatitis B infection at screening 21. Positive test for hepatitis C virus antibody 22. Negative test for varicella zoster virus (VZV)-IgG 23. 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 24. History of active or latent tuberculosis 25. For subjects who may undergo MRI scans: Unable to undergo an MRI scan (eg, 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.
2. (Polish Continuation) 25. For subjects who may undergo MRI scans: Unable to undergo an MRI scan (eg, 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. 1. PK parameters, including maximum observed concentration (Cmax), area under the concentration-time curve from time 0 to 14 days post dose (AUC0-14d) and from time 0 extrapolated to infinity (AUC0-inf), systemic clearance, terminal elimination half-life (t½), and volume of distribution at steady state (Vss)
2. 2. CD20-positive B-cell counts on Days 1, 8, 15, 29, 57, 85, 113, 155, and 197
3. 3. Safety and tolerability assessments, including incidence of adverse events (AEs)/serious adverse events (SAEs)/adverse events of special interest (AESIs) and changes in laboratory parameters and vital signs

Secondary endpoints 5

1. 1. Disease activity endpoints include: − Time to first relapse − Proportion of relapse-free subjects − Annualized relapse rate
2. 2. HRQoL endpoints include: − Change in Euro Quality of Life-5 Dimension Youth (EQ-5D-Y) score − Change in Pediatric Quality of Life Inventory (PedsQL)
3. 3. Change in visual acuity
4. 4. Change in EDSS
5. 5. Presence of anti-drug antibody (ADA)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Horizon Therapeutics Ireland Designated Activity Company

Sponsor organisation

Horizon Therapeutics Ireland Designated Activity Company

Address

70 Saint Stephen's Green

City

Dublin 2

Postcode

D02 E2X4

Country

Ireland

Scientific contact point

Organisation

Horizon Therapeutics Ireland Designated Activity Company

Contact name

Nishi Rampal

Public contact point

Organisation

Horizon Therapeutics Ireland Designated Activity Company

Contact name

Medical information

Third parties 9

Locations

5 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 67 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications