Clinical study testing the efficacy and safety of Ravulizumab in pediatric patients with NMOSD

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alexion Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Genetic Phenomena [G05]

Trial duration

16 Jun 2022 → ongoing

Decision date (initial)

2024-04-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Alexion Pharmaceuticals, Inc., USA

External identifiers

EU CT number

2023-508534-33-00

EudraCT number

2021-006075-42

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Therapy, Efficacy, Pharmacodynamic, Others

To evaluate the efficacy of ravulizumab in pediatric participants with NMOSD

Secondary objectives 1

1. - To evaluate the effect of ravulizumab on disease-related disability in pediatric participants with NMOSD - To evaluate the effect of ravulizumab on neurologic function in pediatric participants with NMOSD - To characterize the PK of treatment with ravulizumab in pediatric participants with NMOSD - To characterize the PD of treatment with ravulizumab in pediatric participants with NMOSD - To assess quality of life based on patient-reported outcomes in pediatric participants with NMOSD based on treatment with Ravulizumab - To evaluate safety of ravulizumab in pediatric participants with NMOSD - To assess immunogenicity to ravulizumab in pediatric participants with NMOSD - Descriptive comparison of ravulizumab data to historical data from a NMOSD observational study (NCT 03766437) to contextualize efficacy data from this study. - To characterize the long-term effect of ravulizumab on efficacy, safety, PK, PD, and immunogenicity

Conditions and MedDRA coding

Neuromyelitis Optica Spectrum Disorder (NMOSD)

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001943-PIP04-20

Plan to share IPD

Yes

IPD plan description

Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Participant must be ≥ 2 to < 18 years of age at the time of signing the informed consent/assent. 2. Participants must be anti-AQP4 Ab-positive and have a diagnosis of NMOSD as defined by the 2015 international consensus diagnostic criteria. 3. 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. 4. Expanded Disability Status Scale (EDSS) score ≤ 7 5. 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. 6. 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. 7. 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. 8. 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 1

1. 1. Known to be human immunodeficiency virus (HIV) positive 2. History of N meningitidis infection 3. Active systemic bacterial, viral, or fungal infection within 14 days prior to Day 1. 4. Hypersensitivity to ravulizumab, murine proteins or to one of the excipients of ravulizumab. 5. Use of rituximab within 3 months prior to Screening 1. 6. 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 7. Use of intravenous immunoglobulin (IVIg) or plasma exchange (PE) within 3 weeks prior to Screening. 8. 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. 9. Use of immunomodulatory therapies for multiple sclerosis within 3 months prior to Screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. - The change from baseline in the annualized relapse rate (ARR) - Time to First Adjudicated On-trial Relapse (TFR)

Secondary endpoints 5

1. Efficacy: - Change from baseline in expanded disability status scale (EDSS) score - Change from baseline in Hauser Ambulation Index (HAI) - The change from baseline in visual acuity at the end of the Primary Treatment Period
2. Efficacy: - The change from baseline in confrontational visual fields at the end of the Primary Treatment Period - The change from baseline in color vision at the end of the Primary Treatment Period
3. PK/PD: - Serum ravulizumab concentrations through the end of the Primary Treatment Period - 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
4. Health-related QoL: - Change from baseline in PedsQL Scales at the end of the Primary Treatment Period
5. Safety: - Incidence of AEs and SAEs - 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 Extension treatment period: The endpoints of the Primary Treatment Period will be evaluated during the Extension Period.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alexion Pharmaceuticals Inc.

Sponsor organisation

Alexion Pharmaceuticals Inc.

Address

121 Seaport Boulevard

City

Boston

Postcode

02210-2050

Country

United States

Scientific contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Public contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Third parties 12

Locations

3 EU/EEA countries · 8 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 48 files

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

Application history

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