RAVULIZUMAB for Neuromyelitis optica spectrum disorder (AQP4-antibody positive)

Inclusion criteria

• {"criterion_text":"- Participant must be ≥ 2 to < 18 years of age at the time of signing the informed consent/assent.\n- Participants must be anti-AQP4 Ab-positive and have a diagnosis of NMOSD as defined by the 2015 international consensus diagnostic criteria.\n- Complement inhibitor treatment-naïve participants must have had at least 1 attack or relapse in the last 12 months prior to the Screening Period. For participants who are on off-label eculizumab, must have had at least 1 attack or relapse in the 12 months prior to first dose of eculizumab.\n- Expanded Disability Status Scale (EDSS) score ≤ 7\n- Eculizumab-experienced participants must be clinically stable per Investigator for 30 days and have been treated with eculizumab for at least 90 days prior to screening with no missed doses within 2 months prior to Day 1 and no interruptions in treatment since start of eculizumab.\n- Participants who enter the study receiving supportive IST(s) (eg, corticosteroid, azathioprine [AZA], mycophenolate mofetil [MMF], methotrexate [MTX], tacrolimus [TAC], cyclosporin [CsA], or cyclophosphamide [CYC]) for the prevention of relapse, either in combination or monotherapy, must be on a stable dosing regimen of adequate duration prior to Screening and remain on a stable dosing regimen during the Screening Period.\n- To reduce the risk of meningococcal infection (Neisseria meningitidis), all participants must be vaccinated against meningococcal infection from serogroups A, C, W 135, and Y within 3 years prior to, or at least 14 days prior to Day 1, according to national/local guidelines. Participants who do not meet this requirement will be vaccinated against meningococcal infection according to national/local guidelines and will receive prophylactic antibiotics for at least 2 weeks after meningococcal vaccination if Day 1 occurs < 2 weeks after initial vaccination.\n- Documented vaccination for Hib and S pneumoniae at least 14 days prior to Day 1 according to national/local guidelines for the applicable age group."}

Exclusion criteria

• {"criterion_text":"- Known to be human immunodeficiency virus (HIV) positive\n- History of N meningitidis infection\n- Active systemic bacterial, viral, or fungal infection within 14 days prior to Day 1.\n- Hypersensitivity to ravulizumab, murine proteins or to one of the excipients of ravulizumab.\n- Use of rituximab within 3 months prior to Screening 1.\n- Currently treated with a biologic medications (other than eculizumab) that may affect immune system functioning, or has stopped treatment with a biologic medication that may affect immune system functioning, and 5 half lives of the medication have not elapsed by the time of the Screening Visit\n- Use of intravenous immunoglobulin (IVIg) or plasma exchange (PE) within 3 weeks prior to Screening.\n- Participation in another investigational drug or investigational device study (other than Study ECU-NMO-303) within 5 half lives of that investigational product (if known) or 30 days before initiation of the first dose of study drug, whichever is longer.\n- Use of immunomodulatory therapies for multiple sclerosis within 3 months prior to Screening."}

Primary endpoints

• {"endpoint_text":"- The change from baseline in the annualized relapse rate (ARR)\n- Time to First Adjudicated On-trial Relapse (TFR)","definition_or_measurement_approach":"Change from baseline in ARR (annualized relapse rate) calculated over the treatment period; time to first adjudicated on-trial relapse measured as time from baseline to first relapse confirmed by adjudication committee."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in expanded disability status scale (EDSS) score\n- Change from baseline in Hauser Ambulation Index (HAI)\n- The change from baseline in visual acuity at the end of the Primary Treatment Period\n- The change from baseline in confrontational visual fields at the end of the Primary Treatment Period\n- The change from baseline in color vision at the end of the Primary Treatment Period\n- Serum ravulizumab concentrations through the end of the Primary Treatment Period\n- Absolute values, change from baseline, and percentage change from baseline for free serum C5 concentrations over time through the end of the Primary Treatment Period\n- Change from baseline in PedsQL Scales at the end of the Primary Treatment Period\n- Incidence of AEs and SAEs\n- Change from baseline in vital signs, physical growth (weight, height, and head circumference [participants ≤ 3 years of age only]), and laboratory parameters at scheduled visits","definition_or_measurement_approach":"EDSS, HAI, visual acuity, visual fields, and color vision measured as change from baseline at specified visits; PK: serum ravulizumab concentrations measured through Primary Treatment Period; PD: free serum C5 absolute and change from baseline; QoL: PedsQL change from baseline; Safety: incidence of adverse events/serious adverse events and change from baseline in vitals, growth parameters and labs."}

Methods

• Site-based recruitment at participating pediatric neurology/neuroimmunology clinics in Spain, France and Italy (site lists and start dates provided in country Part II submissions).
• Use of country-specific recruitment materials: patient posters and PI brochures (K2 and K1 recruitment documents available per country: ES, FR, IT).
• Country-specific reimbursement procedures and forms (Italy K2 documents) to support participation.
• Site training and communication via a central training platform (Firecrest) as indicated in sponsor third-party responsibilities (training platform, document distribution).

Spain

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

26-12-2024

Processing Time Days

290

Number Of Sites

1

Number Of Participants

2

France

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

07-03-2025

Processing Time Days

361

Number Of Sites

4

Number Of Participants

2

Italy

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

18-08-2025

Processing Time Days

525

Number Of Sites

3

Number Of Participants

2

Primary sponsor

Full Name

Alexion Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Parexel International Corp.

Responsibilities

code 11

Name

Fortrea Inc.

Responsibilities

codes 10, 6

Name

Icon Clinical Research Limited

Responsibilities

Training platform (Firecrest), storage, document communication

Name

PPD Development LP

Responsibilities

PK Analysis; ADA Samples Analysis, C5 sample analysis and NAb Analysis

Name

Syneos Health Netherlands B.V.

Responsibilities

codes 1,12,2,8

Name

Almac Clinical Services Limited

Responsibilities

IP Distribution and IXRS

Third parties

• {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"code 11","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"codes 10, 6","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Mayo Collaborative Services LLC","duties_or_roles":"Anti-AQP4 Ab Testing","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Training platform (Firecrest), storage, communication of important documents to participating sites","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"AG Mednet Inc.","duties_or_roles":"Image reader / adjudication / DSMB","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"PK Analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code 6","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"code 8","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"IP Distribution and IXRS","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Syneos Health Netherlands B.V.","duties_or_roles":"codes 1, 12, 2, 8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP (additional entry)","duties_or_roles":"ADA Samples Analysis, C5 sample analysis and NAb Analysis","organisation_type":"Pharmaceutical company"}