Clinical Trial Results:
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
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Summary
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EudraCT number |
2019-001829-26 |
Trial protocol |
ES DE IT |
Global end of trial date |
31 Jul 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Aug 2024
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First version publication date |
17 Aug 2024
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ECU-NMO-303
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04155424 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Alexion Pharmaceuticals Inc.
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Sponsor organisation address |
121 Seaport Boulevard, Boston, MA, United States, 02210
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Public contact |
European Clinical Trial Information, Alexion Pharmaceuticals Inc., +33 147100606, clinicaltrials.eu@alexion.com
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Scientific contact |
European Clinical Trial Information, Alexion Pharmaceuticals Inc., +33 147100606, clinicaltrials.eu@alexion.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000876-PIP03-14 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Jul 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Jul 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jul 2023
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The main 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).
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Protection of trial subjects |
This study was conducted in accordance with the protocol and with the following:
• Consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines
• Applicable International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Guidelines
• Applicable laws and regulations
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Jan 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Japan: 1
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Country: Number of subjects enrolled |
Canada: 2
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Country: Number of subjects enrolled |
Spain: 1
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Country: Number of subjects enrolled |
Italy: 1
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Worldwide total number of subjects |
5
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EEA total number of subjects |
2
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
2
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Adolescents (12-17 years) |
3
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||
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Pre-assignment
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Screening details |
All 5 participants were in the >=40 kilograms (kg) weight cohort at enrollment. Therefore, all 5 participants received the same dose of study drug for the Induction Period and the Maintenance Period as described in the study arm. | ||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||
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Arms
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Arm title
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Eculizumab | ||||||||||||||||||||
Arm description |
Induction Period: Participants received eculizumab (900 milligrams [mg]) via intravenous (IV) infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Eculizumab
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Investigational medicinal product code |
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Other name |
Soliris
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Eculizumab was administered per dose and schedule specified in the arm description.
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Baseline characteristics reporting groups
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Reporting group title |
Eculizumab
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Reporting group description |
Induction Period: Participants received eculizumab (900 milligrams [mg]) via intravenous (IV) infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Eculizumab
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Reporting group description |
Induction Period: Participants received eculizumab (900 milligrams [mg]) via intravenous (IV) infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks. | ||
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End point title |
Change between the Baseline Annualized Relapse Rate (ARR) and the On-Trial ARR at Week 52/53 [1] | ||||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
Baseline, Week 52/53
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The statistical analysis was not planned for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to First On-trial Relapse [2] | ||||||||
End point description |
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. Full Analysis Set included all participants who received at least 1 dose of eculizumab. Note that since no participants experienced an On-trial Relapse, data was not collected for this Outcome Measure.
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End point type |
Primary
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End point timeframe |
Baseline up to Week 52/53
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The statistical analysis was not planned for this endpoint. |
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| Notes [3] - No participants experienced an On-trial Relapse. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from Baseline in Pediatric Quality of Life Inventory (PedsQL) Score at Week 52/53 | ||||||||
End point description |
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. Full Analysis Set included all participants who received at least 1 dose of eculizumab. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 52/53
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With Shift from Baseline in Visual Acuity (VA) | ||||||||||
End point description |
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. Test was performed at a standard distance, typically 6 meters or 20 feet. 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 end of primary treatment period. Data are presented for number of participants with a shift from baseline in VA presented per different levels of acuity ratio distance. Baseline: last available assessment prior to first IP study drug infusion regardless of treatment group. Visual Acuity data are only reported for the categories with available data at Baseline and Week 52/53. Full Analysis Set: all participants who received at least 1 dose of eculizumab. Overall number of participants analyzed= participants evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 52/53
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| No statistical analyses for this end point | |||||||||||
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End point title |
Change from Baseline in Expanded Disability Status Scale (EDSS) Score at Week 52/53 | ||||||||
End point description |
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. Full Analysis Set included all participants who received at least 1 dose of eculizumab. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 52/53
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from Baseline in the Hauser Ambulation Index (HAI) Score at Week 52/53 | ||||||||
End point description |
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. Full Analysis Set included all participants who received at least 1 dose of eculizumab. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 52/53
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With Shift from Baseline in Confrontational Visual Fields (VF) | ||||||||||
End point description |
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. Full Analysis Set included all participants who received at least 1 dose of eculizumab. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 52/53
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| No statistical analyses for this end point | |||||||||||
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End point title |
Number of Participants With Shift from Baseline in Color Vision | ||||||||||
End point description |
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. Full Analysis Set included all participants who received at least 1 dose of eculizumab. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 52/53
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| No statistical analyses for this end point | |||||||||||
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End point title |
Serum Eculizumab Concentration at Week 52 | ||||||||||||
End point description |
Pharmacokinetic/Pharmacodynamic (PK/PD) analysis set included participants who received at least 1 dose of eculizumab and who had evaluable PK/PD data for the endpoint.
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End point type |
Secondary
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End point timeframe |
Week 52
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Serum Free Complement Protein 5 (C5) Concentrations at Week 52 | ||||||||||||
End point description |
PK/PD analysis set included participants who received at least 1 dose of eculizumab and who had evaluable PK/PD data. for the endpoint. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure .
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End point type |
Secondary
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End point timeframe |
Baseline, Week 52
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to Week 53
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Adverse event reporting additional description |
Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.0
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Reporting groups
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Reporting group title |
Eculizumab
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Reporting group description |
Induction Period: Participants received eculizumab (900 mg) via IV infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Notes [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The N for this adverse event has been adjusted to the number of females in the study as it is a sex-specific event. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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08 Jul 2019 |
It included following changes:
- The study enrollment criteria on vaccination against meningococcal infections was updated to clarify that all participants must be vaccinated against meningococcal infections within the 3 years prior to, or at the time of, initiating study intervention. Participants who initiated study intervention treatment less than 2 weeks after receiving a meningococcal vaccine were to receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Participants were also to be vaccinated or revaccinated according to current national vaccination guidelines or local practice for vaccination use with complement-inhibitors (for example, eculizumab) instead of staying within the manufacturer's guidelines for vaccination times.
- The study enrollment criterion on vaccination against Haemophilus influenzae and Streptococcus pneumoniae infections was updated to mention that this vaccination should be performed at least 2 weeks prior to dosing as per local and country-specific immunization guidelines for the appropriate age group. |
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03 May 2021 |
It included following changes:
- The total sample size was decreased for the study based on updated sample size calculations. The number of participants enrolled was reduced from 15 to 12, and the number of evaluable participants for the primary analysis was reduced from 12 to 10.
- Electrocardiograms (ECG) assessment was added to Week 26 for participants ≥ 20 kg, and added to Week 27 for participants 10 to < 20 kg.
- Added text to clarify that vaccination was to be administered per local and country specific immunization guidelines for appropriate age groups.
- Text was added to specify that supportive immunosuppressive therapies (ISTs) was to remain stable during the Screening Period.
- Exclusion criterion was updated to clarify that a potential participant with active bacterial, viral, or fungal infection within 14 days prior to study intervention administration was to be excluded.
- Exclusion criterion was added to exclude participants currently treated with a biologic medication that may affect immune system functioning. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The study was terminated by Alexion, as only 5 of the planned 12 participants were enrolled due to difficulty in recruitment. | |||
