Neuromyelitis OpticaPhase 2/3NCT04155424
A Study of the Safety and Activity of Eculizumab in Pediatric Participants With Relapsing Neuromyelitis Optica Spectrum Disorder
A Phase 2/3 study testing Eculizumab in people with Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorder, run by Alexion Pharmaceuticals, Inc. at 35 sites in 7 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Neuromyelitis Optica, Neuromyelitis Optica Spectrum Disorder
- What is being tested?
- Eculizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 35 sitesin 7 countries
- Study dates
- 14 Jan 2020to 31 Jul 2023
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female participants aged 2 years to < 18 years with body weight ≥ 10 kilograms (kg).
- 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.
- 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.
- Anti-aquaporin-4 antibody-positive and diagnosis of NMOSD as defined by the 2015 International Panel for Neuromyelitis Optica Diagnosis criteria.
- 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.
- EDSS score ≤ 7.
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- 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.
- 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.
- 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.
Who cannot join
- Parent or legal guardian is an Alexion employee.
- Pregnant, breastfeeding, or intending to conceive during the course of the study.
- Participants known to be human immunodeficiency virus positive or with congenital immunodeficiency.
- Unresolved meningococcal or other serious infection.
- 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.
- Use of rituximab or other biologicals such as tocilizumab within 6 months prior to Screening.
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- Use of mitoxantrone within 3 months prior to Screening.
- Use of intravenous immunoglobulin or plasma exchange within 3 weeks prior to Screening.
- Use of immunomodulatory therapies for multiple sclerosis within 3 months prior to Screening.
- Has previously received treatment with eculizumab or other complement inhibitors.
Trial locations and contacts
35 sites in 7 countries.
35 sites in 7 countries
United States15 sites
Clinical Trial Site
Atlanta, Georgia, 30301
Research Site
Baltimore, Maryland, 21287
Clinical Trial Site
Boston, Massachusetts, 02101
Research Site
Boston, Massachusetts, 02115
Clinical Trial Site
Chapel Hill, North Carolina, 27514
Research Site
Dallas, Texas, 75390
Research Site
Hackensack, New Jersey, 07601
Clinical Trial Site
Miami, Florida, 33101
Research Site
New Brunswick, New Jersey, 08901
Research Site
New York, New York, 10016
Clinical Trial Site
Philadelphia, Pennsylvania, 19019
Clinical Trial Site
Rockville, Maryland, 20847
Clinical Trial Site
San Francisco, California, 94016
Research Site
St Louis, Missouri, 63130
Clinical Trial Site
Washington D.C., District of Columbia, 20001
Italy6 sites
Research Site
Catania, 95123
Research Site
Gallarate, 21013
Clinical Trial Site
Genoa
Research Site
Genova, 16132
Research Site
Rome, 00178
Clinical Trial Site
Rome
Canada5 sites
Research Site
Calgary, Alberta, T3B 6A8
Clinical Trial Site
Edmonton, Alberta
Research Site
Montreal, Quebec, H3T1C5
Research Site
Toronto, Ontario, M5G 1X8
Clinical Trial Site
Toronto, Ontario
Germany3 sites
Research Site
Datteln, 45711
Research Site
Münster, 48149
Clinical Trial Site
Regensburger Straße, Goettingen
Spain3 sites
Clinical Trial Site
Barcelona
Research Site
Esplugues de Llobregat, 8950
Clinical Trial Site
Seville
About this study
Official title: 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).
- Being tested
- Eculizumab
- Keywords
- Neuromyelitis Optica, Neuromyelitis Optica Spectrum Disorder, Devic's Disease, Transverse Myelitis, Optic Neuritis, Relapse, Eculizumab, Soliris, CNS Autoimmune Disorders, Demyelinating Disorders, NMO, NMOSD
- Medical subject headings
- Neuromyelitis Optica, Myelitis, Transverse, Optic Neuritis, Recurrence, Demyelinating Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EculizumabDrug
Also called Soliris
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.
| Study group | Role | What they receive |
|---|---|---|
| Eculizumab | Experimental | 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. Receives: Drug: Eculizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline up to Week 52/53
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, Weeks 52/53
Serum Eculizumab Concentration at Week 52
Measured: Week 52
Change From Baseline in Serum Free Complement Protein 5 (C5) Concentrations at Week 52
Measured: Baseline, Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2019
- Study start14 Jan 2020
- Primary completion31 Jul 2023
- Study completion31 Jul 2023
Why it stopped: Pediatric clinical study is not feasible.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neuromyelitis OpticaStudies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04155424
- Sponsor's protocol ID
- ECU-NMO-303
- Other IDs
- 2019-001829-26, 2019
- Status last verified
- Sep 2024
- First submitted
- 5 Nov 2019
- Last updated
- 25 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04155424
- Acronym / sponsor ID
- ECU-NMO-303
- Keywords
- Neuromyelitis Optica, Neuromyelitis Optica Spectrum Disorder, Devic's Disease, Transverse Myelitis, Optic Neuritis, Relapse, Eculizumab, Soliris
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Pediatric clinical study is not feasible.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 14 Jan 2020 (actual)
- Primary completion
- 31 Jul 2023 (actual)
- Study completion
- 31 Jul 2023 (actual)
- First posted
- 7 Nov 2019 (actual)
- Results
- Posted 25 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eculizumab | Experimental | Drug: EculizumabAll 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female participants aged 2 years to < 18 years with body weight ≥ 10 kilograms (kg).
- 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.
- 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.
- Anti-aquaporin-4 antibody-positive and diagnosis of NMOSD as defined by the 2015 International Panel for Neuromyelitis Optica Diagnosis criteria.
- 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.
Key exclusion criteria (10 listed)
- Parent or legal guardian is an Alexion employee.
- Pregnant, breastfeeding, or intending to conceive during the course of the study.
- Participants known to be human immunodeficiency virus positive or with congenital immunodeficiency.
- Unresolved meningococcal or other serious infection.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EculizumabAlso: SolirisFollowing 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. | Drug | Eculizumab |
Primary outcome
Change Between the Baseline Annualized Relapse Rate (ARR) and the On-Trial ARR at Week 52/53
Time frame: Baseline, 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.
Time to First On-trial Relapse
Time frame: Baseline up to Week 52/53
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.
8 secondary outcomes
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 52/53
Time frame: Baseline, Week 52/53
Change From Baseline in the Hauser Ambulation Index (HAI) Score at Week 52/53
Time frame: Baseline, Weeks 52/53
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Score at Week 52/53
Time frame: Baseline, Weeks 52/53
Number of Participants With Shift From Baseline in Visual Acuity (VA)
Time frame: Baseline, Week 52/53
Number of Participants With Shift From Baseline in Confrontational Visual Fields (VF)
Time frame: Baseline, Weeks 52/53
Number of Participants With Shift From Baseline in Color Vision
Time frame: Baseline, Weeks 52/53
Serum Eculizumab Concentration at Week 52
Time frame: Week 52
Change From Baseline in Serum Free Complement Protein 5 (C5) Concentrations at Week 52
Time frame: Baseline, Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
35 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Eculizumab in people with Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorder, run by Alexion Pharmaceuticals, Inc. at 35 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, Italy, Canada, Germany, Spain and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change Between the Baseline Annualized Relapse Rate (ARR) and the On-Trial ARR at Week 52/53 (time frame: Baseline, Week 52/53). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2024.