A Study of the Safety and Activity of Eculizumab in Pediatric Participants With Relapsing Neuromyelitis Optica Spectrum Disorder

A Phase 2/3 Open-Label, Single-Arm Trial to Evaluate the Safety and Activity of Eculizumab in Pediatric Patients With Relapsing Neuromyelitis Optica Spectrum Disorder

The objective of this study is to evaluate the safety and efficacy of eculizumab in pediatric participants (aged 2 to < 18 years) with relapsing neuromyelitis optica spectrum disorder (NMOSD).

Study Overview

• Status: Terminated
• Conditions: Neuromyelitis Optica; Neuromyelitis Optica Spectrum Disorder
• Intervention / Treatment: Drug: Eculizumab

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Research Site
    • Edmonton, Alberta, Canada
      • Clinical Trial Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Research Site
    • Toronto, Ontario, Canada
      • Clinical Trial Site
  • Quebec
    • Montreal, Quebec, Canada, H3T1C5
      • Research Site
• Germany
  • Datteln, Germany, 45711
    • Research Site
  • Munster, Germany, 48149
    • Research Site
  • Goettingen
    • Regensburger Straße, Goettingen, Germany
      • Clinical Trial Site
• Italy
  • Catania, Italy, 95123
    • Research Site
  • Gallarate, Italy, 21013
    • Research Site
  • Genoa, Italy
    • Clinical Trial Site
  • Genova, Italy, 16132
    • Research Site
  • Rome, Italy
    • Clinical Trial Site
  • Rome, Italy, 00178
    • Research Site
• Japan
  • Yokohama, Japan
    • Clinical Trial Site
  • Yokohama-shi, Japan, 232-0024
    • Research Site
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Clinical Trial Site
• Spain
  • Barcelona, Spain
    • Clinical Trial Site
  • Esplugues de Llobregat, Spain, 8950
    • Research Site
  • Sevilla, Spain
    • Clinical Trial Site
• United States
  • California
    • San Francisco, California, United States, 94016
      • Clinical Trial Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20001
      • Clinical Trial Site
  • Florida
    • Miami, Florida, United States, 33101
      • Clinical Trial Site
  • Georgia
    • Atlanta, Georgia, United States, 30301
      • Clinical Trial Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Research Site
    • Rockville, Maryland, United States, 20847
      • Clinical Trial Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Research Site
    • Boston, Massachusetts, United States, 02101
      • Clinical Trial Site
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Research Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Research Site
    • New Brunswick, New Jersey, United States, 08901
      • Research Site
  • New York
    • New York, New York, United States, 10016
      • Research Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Clinical Trial Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19019
      • Clinical Trial Site
  • Texas
    • Dallas, Texas, United States, 75390
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female participants aged 2 years to < 18 years with body weight ≥ 10 kilograms (kg).
2. Vaccinated against Neisseria meningitidis within 3 years prior to, or at the time of initiating eculizumab. Participants who initiate study drug treatment less than 2 weeks after receiving a meningococcal vaccine must receive appropriate prophylactic antibiotics until 2 weeks after the vaccination.
3. Documented vaccination against haemophilus influenzae type b and streptococcus pneumoniae infections at least 2 weeks prior to dosing as per local and country-specific immunization guidelines for the appropriate age group.
4. Anti-aquaporin-4 antibody-positive and diagnosis of NMOSD as defined by the 2015 International Panel for Neuromyelitis Optica Diagnosis criteria.
5. Historical Relapse Rate of at least 2 relapses in the last 2 years, and with at least 1 relapse in the year prior to Screening.
6. EDSS score ≤ 7.
7. Participants who enter the study receiving supportive immunosuppressive therapies (ISTs) for the prevention of relapse, either in combination or monotherapy, must be on a stable dosing regimen of adequate duration.
8. Female participants of childbearing potential must have a negative pregnancy test (serum human chorionic gonadotropin) at Screening and follow protocol-specified contraception guidance for avoiding pregnancy while on treatment and for 5 months after the last dose of eculizumab.
9. Male participants with a female spouse/partner of childbearing potential or a pregnant or breastfeeding spouse or partner must agree to use double barrier contraception (male condom plus appropriate barrier method for the female partner) while on treatment and for at least 5 months after the last dose of eculizumab.

Exclusion Criteria:

1. Parent or legal guardian is an Alexion employee.
2. Pregnant, breastfeeding, or intending to conceive during the course of the study.
3. Participants known to be human immunodeficiency virus positive or with congenital immunodeficiency.
4. Unresolved meningococcal or other serious infection.
5. Any unresolved acute or chronic systemic bacterial or other infection that is clinically significant in the opinion of the Investigator and has not been treated with appropriate antibiotics.
6. Use of rituximab or other biologicals such as tocilizumab within 6 months prior to Screening.
7. Use of mitoxantrone within 3 months prior to Screening.
8. Use of intravenous immunoglobulin or plasma exchange within 3 weeks prior to Screening.
9. Use of immunomodulatory therapies for multiple sclerosis within 3 months prior to Screening.
10. Has previously received treatment with eculizumab or other complement inhibitors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Eculizumab; All participants will receive open-label eculizumab by intravenous infusion during the Primary Treatment Period, starting on Day 1 and for a total of 52/53 weeks. The dosing regimen will be based on the participant's body weight. As body weight changes during the study, the participant's weight cohort and dose may change accordingly. After completing the 52/53-week Primary Treatment Period, participants may continue receiving eculizumab in the Extension Treatment Period for 104 weeks.

Drug: Eculizumab; Following a weight-based weekly dose of eculizumab during an induction phase, participants will receive weight-based doses of eculizumab every 2 weeks during the Primary Treatment Period and Extension Treatment Period.; Other Names: Soliris

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change Between the Baseline Annualized Relapse Rate (ARR) and the On-Trial ARR at Week 52/53	ARR was calculated as the number of relapses for each participant divided by the number of years of treatment for that participant. Baseline ARR was based on 24 months prior to screening.	Baseline, Week 52/53
Time to First On-trial Relapse	Time to First Relapse was defined as beginning at the time the participant's first dose of eculizumab was administered until the participant's first on-trial relapse was reported by the Investigator. Participants who did not experience an on-trial relapse were censored at the end of the study period.	Baseline up to Week 52/53

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 52/53	Disease-related disability was measured by the EDSS. The EDSS is an ordinal clinical rating scale that ranges from 0 (normal neurologic examination) to 10 (death) in half-point increments. A decrease in score indicates improvement.	Baseline, Week 52/53
Change From Baseline in the Hauser Ambulation Index (HAI) Score at Week 52/53	The HAI evaluates gait and was used to assess the time and effort used by the participant to walk 25 feet (8 meters). The scale ranged from 0 to 9, with 0 being the best score (asymptomatic; fully ambulatory with no assistance) and 9 being the worst (restricted to wheel chair; unable to transfer self independently). A decrease in score indicates improvement.	Baseline, Weeks 52/53
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Score at Week 52/53	PedsQL included a child self-report for participants 5 to 18 years with a 23-item PedsQL Generic Core Scales report. The PedsQL Generic Core Scales report included 4 scales, physical functioning, emotional functioning, social functioning, and school functioning. Each item used a 5-point rating scale (from 0=never to 4=almost always). Items are reverse scored and linearly transformed to a 0 (almost always) -100 (never) scale. All summary/total scores were mean of specific items where higher score indicated better HRQoL.	Baseline, Weeks 52/53
Number of Participants With Shift From Baseline in Visual Acuity (VA)	The Snellen chart was used to assess VA. The Snellen chart quantifies ability to read letters of varying sizes at a fixed distance in relation to the distance at which a participant with normal vision could read the same letters. The test was performed at a standard distance, typically 6 meters or 20 feet. The Snellen chart is typically recorded as acuity ratio distance (6 meters or 20 feet), so for normal VA it would be recorded as 20/20 or 6/6. Visual acuity was summarized according to the eye with greater worsening at the end of primary treatment period (Week 52/53). Data are presented for number of participants with a shift from baseline in VA presented per the different levels of acuity ratio distance. Baseline was defined as the last available assessment prior to the first IP study drug infusion for all participants regardless of treatment group. Visual Acuity data are only reported for the categories with available data at Baseline and Week 52/53.	Baseline, Week 52/53
Number of Participants With Shift From Baseline in Confrontational Visual Fields (VF)	Confrontational visual fields were summarized according to the number of quadrants with deficits across both eyes. Baseline was defined as the last available assessment prior to the first IP study drug infusion for all participants regardless of treatment group.	Baseline, Weeks 52/53
Number of Participants With Shift From Baseline in Color Vision	Color vision was evaluated as the shift from baseline and described for participants with normal color vision at baseline in at least one eye. Participants with 13 or less correctly identified Ishihara plates were considered as having abnormal color vision, participants with 14 or more correctly identified plates were considered as having normal color vision. Baseline was defined as the last available assessment prior to the first IP study drug infusion for all participants regardless of treatment group.	Baseline, Weeks 52/53
Serum Eculizumab Concentration at Week 52		Week 52
Change From Baseline in Serum Free Complement Protein 5 (C5) Concentrations at Week 52		Baseline, Week 52

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2020
• Primary Completion (Actual): July 31, 2023
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: November 5, 2019
• First Submitted That Met QC Criteria: November 5, 2019
• First Posted (Actual): November 7, 2019

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 19, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Relapse; Eculizumab; Optic Neuritis; Transverse Myelitis; NMO; Neuromyelitis Optica Spectrum Disorder; Neuromyelitis Optica; Soliris; CNS Autoimmune Disorders; NMOSD; Devic's Disease; Demyelinating Disorders
• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Eye Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Myelitis, Transverse; Optic Neuritis; Neuromyelitis Optica; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Eculizumab
• Other Study ID Numbers: ECU-NMO-303; 2019-001829-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No