Inebilizumab for Neuromyelitis optica spectrum disorder (NMOSD)

Inclusion criteria

• {"criterion_text":"- 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.\n- 2. Male or female subjects, minimum body weight of 15 kg, age 2 to < 18 years at the time of screening.\n- 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\n- 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.\n- 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)\n- 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

• {"criterion_text":"- 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\n- 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\n- 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\n- 4. Known history of allergy or reaction to any component of the IP formulation or history of anaphylaxis following any biologic therapy \n- 5. Evidence of alcohol, drug, or chemical abuse, or a recent history of such abuse < 1 year prior to Day 1\n- 6. Major surgery within 8 weeks prior to screening\n- 7. Spontaneous or induced abortion, still or live birth, or pregnancy ≤ 4 weeks prior to screening\n- 8. Evidence of significant hepatic, renal, or metabolic dysfunction or significant hematological abnormality\n- 9. B-cell counts < one-half of the lower limit of normal (LLN) for age according to the central laboratory\n- 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 \n- 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.\n- 12. Receipt of intravenous immunoglobulin (IVIG) within one month prior to Day 1\n- 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 \n- 14. Receipt of natalizumab (Tysabri®) within 6 months prior to Day 1\n- 15. Severe drug allergic history or anaphylaxis to 2 or more food products or medicine\n- 16. Diagnosed with a concurrent autoimmune disease that is uncontrolled (unless approved by the medical monitor)\n- 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\n- 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\n- 19. Known history of congenital or acquired immunodeficiency that predisposes the subject to infection\n- 20. Positive test for chronic hepatitis B infection at screening\n- 21. Positive test for hepatitis C virus antibody\n- 22. Negative test for varicella zoster virus (VZV)-IgG\n- 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\n- 24. History of active or latent tuberculosis\n- 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."}

Primary endpoints

• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Measurement of plasma PK parameters (Cmax, AUC0-14d, AUC0-inf, systemic clearance, terminal t½, Vss) from blood samples collected per protocol and analysed by central laboratory/PK assays."}
• {"endpoint_text":"- 2. CD20-positive B-cell counts on Days 1, 8, 15, 29, 57, 85, 113, 155, and 197","definition_or_measurement_approach":"Enumeration of CD20-positive B cells at specified timepoints (Days 1, 8, 15, 29, 57, 85, 113, 155, 197) using laboratory cell-count assays (central laboratory)."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Collection and reporting of AEs/SAEs/AESIs throughout the study, periodic laboratory tests, and vital signs assessments per schedule to assess safety and tolerability."}

Secondary endpoints

• {"endpoint_text":"- 1. Disease activity endpoints include: − Time to first relapse − Proportion of relapse-free subjects − Annualized relapse rate","definition_or_measurement_approach":"Time-to-event analysis for time to first relapse; calculation of proportion of subjects without relapse; calculation of annualized relapse rate from recorded relapse events per subject-year."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Change from baseline in EQ-5D-Y and PedsQL scores assessed at scheduled visits using validated questionnaires."}
• {"endpoint_text":"- 3. Change in visual acuity","definition_or_measurement_approach":"Assessment of visual acuity changes from baseline using standard ophthalmologic visual acuity testing."}
• {"endpoint_text":"- 4. Change in EDSS","definition_or_measurement_approach":"Change from baseline in Expanded Disability Status Scale (EDSS) score assessed by qualified assessors per schedule."}
• {"endpoint_text":"- 5. Presence of anti-drug antibody (ADA)","definition_or_measurement_approach":"Assessment of immunogenicity by measuring anti-drug antibodies (ADA) in blood samples using validated assays."}

Methods

• HCP referral letters (documents include HCP-Referral-Letter files) to engage treating clinicians for patient identification (country-specific versions available).
• Patient letters and information leaflets (Patient-Letter and Understanding the I-CAN-Study) provided to potential participants/families (country-specific materials available e.g., ES, PL, SE, NL, FRA).
• Investigator-facing materials and site flip-charts (IA-Flip-Chart, Study Schedule Planners) to support site-based recruitment and information delivery.
• Scout pre-ICF telephone contact (Scout-Pre-ICF-Telephone-Data-Consent documents) indicating telephone pre-screening/consent procedures for initial contact and data consent.
• Managed patient support/concierge services (third-party patient concierge and travel/transportation services listed among sponsor third parties) to facilitate participation and visits.

Poland

Earliest CTIS Part Ii Submission Date

26-04-2024

Latest Decision Or Authorization Date

20-05-2024

Processing Time Days

24

Number Of Sites

1

Number Of Participants

1

Spain

Earliest CTIS Part Ii Submission Date

26-04-2024

Latest Decision Or Authorization Date

14-05-2024

Processing Time Days

18

Number Of Sites

1

Number Of Participants

1

Sweden

Earliest CTIS Part Ii Submission Date

26-04-2024

Latest Decision Or Authorization Date

14-05-2024

Processing Time Days

18

Number Of Sites

1

Number Of Participants

1

France

Earliest CTIS Part Ii Submission Date

26-04-2024

Latest Decision Or Authorization Date

17-05-2024

Processing Time Days

21

Number Of Sites

1

Number Of Participants

1

Netherlands

Earliest CTIS Part Ii Submission Date

26-04-2024

Latest Decision Or Authorization Date

14-05-2024

Processing Time Days

18

Number Of Sites

1

Number Of Participants

1

Primary sponsor

Full Name

Horizon Therapeutics Ireland Designated Activity Company

Organisation Type

Pharmaceutical company

Country Of Registered Address

Ireland

Contract research organisations

Name

PPD Development L.P.

Responsibilities

Clinical operations, patient concierge services, safety reporting and other operational roles (sponsor duties codes: 1,12,15,5,6,8)

Name

PPD Slovak Republic s.r.o.

Responsibilities

Global clinical supplies, safety reporting (PVG) and operational support

Name

Icon Development Solutions Limited

Responsibilities

PVG services and DSUR submission support

Name

Pharmaceutical Product Development LLC

Responsibilities

Patient concierge services

Name

Suvoda LLC

Responsibilities

IRT software and services

Name

Scout Clinical

Responsibilities

Patient travel and expenses management

Name

Jumo Health USA Inc.

Responsibilities

Educational materials and patient/site flyers management

Third parties

• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"This site is responsible for certification of each IMP including placebo","organisation_type":"Pharmaceutical company"}
• {"country":"Israel","full_name":"Transcom Global Ltd.","duties_or_roles":"Educational services patient","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development L.P.","duties_or_roles":"Patient concierge service; additional operational roles (sponsor duties codes: 1,12,5,6,8)","organisation_type":"Pharmaceutical company"}
• {"country":"Slovakia","full_name":"PPD Slovak Republic s.r.o.","duties_or_roles":"Global Clinical Supplies, Safety Reporting (PVG); operational roles","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"IRT software and services","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Icon Development Solutions Limited","duties_or_roles":"PVG services to support study; DSUR submission","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Jumo Health USA Inc.","duties_or_roles":"Educational services (patient/site flyers/sheets) management services","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient travel, ground transportation and expense management services","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"Patient concierge service","organisation_type":"Pharmaceutical company"}