Clinical Trial Results:
An Open-Label, Multicenter Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Eculizumab in Pediatric Patients with Refractory Generalized Myasthenia Gravis
|
Summary
|
|
EudraCT number |
2016-001384-37 |
Trial protocol |
DE NL |
Global end of trial date |
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
16 Jul 2022
|
First version publication date |
16 Jul 2022
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
ECU-MG-303
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT03759366 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Alexion Pharmaceuticals Inc.
|
||
Sponsor organisation address |
100 College Street, New Haven, CT, United States, 06510
|
||
Public contact |
Alexion Europe SAS European Clinical Trial Information, Alexion Pharmaceuticals Inc., +33 7 87148158, clinicaltrials.eu@alexion.com
|
||
Scientific contact |
Alexion Europe SAS European Clinical Trial Information, Alexion Pharmaceuticals Inc., +33 7 87148158, clinicaltrials.eu@alexion.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-000876-PIP05-15 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Interim
|
||
Date of interim/final analysis |
06 Jan 2022
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
06 Jan 2022
|
||
Global end of trial reached? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The main objective of this trial was to evaluate the efficacy of eculizumab in the treatment of pediatric refractory generalized Myasthenia Gravis (gMG) based on change from baseline in the Quantitative Myasthenia Gravis (QMG) total score for disease severity.
|
||
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
|
||
Background therapy |
Participants could continue to receive acetylcholinesterase inhibitor (AChI), intravenous immunoglobulin (IVIg), and immunosuppressant therapies (ISTs) during the study, where applicable, under certain restrictions. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Dec 2018
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United States: 8
|
||
Country: Number of subjects enrolled |
Japan: 3
|
||
Worldwide total number of subjects |
11
|
||
EEA total number of subjects |
0
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
11
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
|||||||||||
|
Recruitment
|
|||||||||||
Recruitment details |
The study included a Primary Evaluation Treatment Period of 26 weeks, an Extension Period of up to an additional 208 weeks, and a Follow-up Period of 8 weeks. All participants were offered participation in the Extension Period of the study. | ||||||||||
|
Pre-assignment
|
|||||||||||
Screening details |
Interim results at data cut-off date 06 January 2022 has been reported. Final results will be posted after study completion. | ||||||||||
|
Period 1
|
|||||||||||
Period 1 title |
Primary Evaluation Period (26 Weeks)
|
||||||||||
Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
|
||||||||||
Blinding used |
Not blinded | ||||||||||
|
Arms
|
|||||||||||
|
Arm title
|
Eculizumab | ||||||||||
Arm description |
Participants received eculizumab weekly by intravenous (IV) infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 milligrams (mg), based on the participant's current body weight. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Eculizumab
|
||||||||||
Investigational medicinal product code |
|||||||||||
Other name |
|||||||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
||||||||||
Routes of administration |
Intravenous use
|
||||||||||
Dosage and administration details |
Eculizumab was administered per dose and schedule specified in the protocol.
|
||||||||||
|
|||||||||||
|
Period 2
|
|||||||||||
Period 2 title |
Extension Period (Up to 208 Weeks)
|
||||||||||
Is this the baseline period? |
No | ||||||||||
Allocation method |
Not applicable
|
||||||||||
Blinding used |
Not blinded | ||||||||||
|
Arms
|
|||||||||||
|
Arm title
|
Eculizumab | ||||||||||
Arm description |
Participants received eculizumab weekly by intravenous (IV) infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 milligrams (mg), based on the participant's current body weight. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Eculizumab
|
||||||||||
Investigational medicinal product code |
|||||||||||
Other name |
|||||||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
||||||||||
Routes of administration |
Intravenous use
|
||||||||||
Dosage and administration details |
Eculizumab was administered per dose and schedule specified in the protocol.
|
||||||||||
|
|||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Eculizumab
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received eculizumab weekly by intravenous (IV) infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 milligrams (mg), based on the participant's current body weight. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Eculizumab
|
||
Reporting group description |
Participants received eculizumab weekly by intravenous (IV) infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 milligrams (mg), based on the participant's current body weight. | ||
Reporting group title |
Eculizumab
|
||
Reporting group description |
Participants received eculizumab weekly by intravenous (IV) infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 milligrams (mg), based on the participant's current body weight. | ||
|
|||||||||
End point title |
Change From Baseline in the QMG Total Score at Week 26 Regardless of Rescue Treatment [1] | ||||||||
End point description |
The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher score indicating more severe disease. Modified full analysis set (mFAS) included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Baseline, Week 26
|
||||||||
| 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: Due to single arm, statistical analysis could not be reported. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Total Score at Week 26 Regardless of Rescue Treatment | ||||||||
End point description |
The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living in participants with myasthenia gravis (MG). The 8 items of the MG-ADL are derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded from 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 to 24, with higher score indicating more severe disease. mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline, Week 26
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score With No Rescue Treatment | ||||||||
End point description |
The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living in participants with MG. The 8 items of the MG-ADL are derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded from 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 to 24, with higher score indicating more severe disease. mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Week 26
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score Regardless of Rescue Treatment | ||||||||
End point description |
The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living in participants with MG. The 8 items of the MG-ADL are derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded from 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 to 24, with higher score indicating more severe disease. mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Week 26
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Participants With ≥5-Point Reduction in the QMG Total Score With No Rescue Treatment | ||||||||
End point description |
The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher score indicating more severe disease. mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Week 26
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Change From Baseline in the Myasthenia Gravis Composite (MGC) Scale Total Score at Week 26 Regardless of Rescue Treatment | ||||||||
End point description |
The MGC is a validated assessment tool for measuring clinical status of participants with MG. The MGC assesses 10 important functional areas most frequently affected by MG: ocular (2 items), facial (1 item), bulbar (3 items), respiratory (1 item), axial (1 item), and gross motor (2 items). The scales are weighted for clinical significance that incorporates patient-reported outcomes. The MGC total score ranges from 0 to 50, with lower scores indicating less functional impairment and higher scores indicating greater functional impairment. mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline, Week 26
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Participants With ≥5-Point Reduction in the QMG Total Score Regardless of Rescue Treatment | ||||||||
End point description |
The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher score indicating more severe disease. mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Week 26
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Change From Baseline in the European Quality of Life 5-Dimension Youth version (EQ-5D-Y) Scale Score at Week 26 Regardless of Rescue Treatment | ||||||||
End point description |
The EQ-5D-Y is a reliable and validated survey of health status in 5 areas: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, each of which is completed by the participant for participants ≥12 years of age (at time of assessment) and completed by the participant’s caregiver or with caregiver assistance for participant <12 years of age. Each area has 3 levels: Level 1 (no problems), Level 2 (some problems), and Level 3 (extreme problems). The EQ visual analogue scale (VAS) records the participant’s self-rated health on a vertical, 20 cm VAS where the endpoints are labelled ‘Best imaginable health state, marked as 100’ and ‘Worst imaginable health state, marked as 0’. mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline, Week 26
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Change From Baseline in the Neurological Quality of Life-Fatigue Questionnaire (Neuro-QoL Pediatric Fatigue) Total Score at Week 26 Regardless of Rescue Treatment | ||||||||
End point description |
The Neuro-QoL Pediatric Fatigue questionnaire is a reliable and validated brief 11-item survey of fatigue, completed by the participant for participants ≥12 years of age (at time of assessment) and completed by the participant's caregiver or with caregiver assistance for participants <12 years of age. Each item was scored on a scale of 1 to 5 (1=Not at all, 2=A little bit, 3=Somewhat, 4=Quite a bit, 5=Very much). Total score is the sum of each item’s score and it ranges from 11 to 55. Higher scores indicate greater fatigue and greater impact of MG on activities. mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline, Week 26
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Number of Participants in Each Category of the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFAPIS) Regardless of Rescue Treatment at Week 26 | ||||||||||||
End point description |
The MG clinical state (improved, unchanged, and worse) was assessed using the MGFAPIS. mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 26
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||
End point title |
Percentage of Participants With Clinical Deteriorations, Myasthenic Crises, and Rescue Therapy Use | ||||||||||||||
End point description |
Rescue therapy (for example, high dose corticosteroid, plasma exchange [PE], or intravenous immunoglobulin [IVIg]) was to be allowed when a participant experienced clinical deterioration. Clinical deterioration was defined as follows: Participants who experienced an MG crisis, which was defined as weakness due to MG that was severe enough to necessitate intubation or to delay extubation following surgery; or, Significant symptomatic worsening that required rescue medication in the opinion of the Investigator; or, Participants for whom the Investigator believed that the participants’ health was in jeopardy if rescue therapy was not given. mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Baseline up to Week 26
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||||
End point title |
Pharmacokinetics (PK): Serum Concentration Of Eculizumab | ||||||||||||||||
End point description |
PK analysis set included participants who had PK data assessments during this study. Here, n = participants evaluable at specified timepoint.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||
End point title |
Pharmacodynamics (PD): Serum Free Complement Component 5 (C5) Concentrations | ||||||||||||||||||
End point description |
PD analysis set included participants who had PD data assessments during this study. Here, n = participants evaluable at specified timepoint.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline; 24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
PD: Percentage of Hemolysis (In Vitro Assay) | ||||||||||||||||||
End point description |
PD analysis set included participants who had PD data assessments during this study. Here, 'Overall number of participants analyzed' = participants evaluable for this endpoint. n = participants evaluable at specified timepoint.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline; 24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Baseline up to the data cut-off date 6 January 2022 (up to approximately 3 years)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Safety analysis set included all participants who received at least 1 dose of eculizumab.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Eculizumab
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received eculizumab weekly by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
17 Sep 2018 |
The purpose of this amendment was:
• To enhance clarity of guidance around the supplemental dosage regimen of eculizumab in participants receiving maintenance IVIg.
• To enhance clarity of guidance around duration of study drug administration for adult and pediatric participants.
• To enhance clarity of guidance around duration of study drug administration in the event of an adverse event (AE) in adult and pediatric participants.
• To align the section regarding acceptable forms of contraception with the current guidance from Heads of Medicine Agency Clinical Trial Facilitation Group .
• To update the QMG testing form to reflect current version. |
||
16 Jul 2019 |
The purpose of this amendment was:
• To change the “Neuro-QoL Pediatric Proxy” assessment to the “PROMIS Parent Proxy Short Form v2.0 – Fatigue 10a” assessment.
• To specify the proxy versions for Neuro-QoL Pediatric Fatigue and EQ-5D-Y assessments in the Schedule of Assessments (SoAs).
• To update the vaccination requirement for N. meningitidis to within 3 years of study start.
• To clarify the inclusion criterion regarding the QMG score at Screening.
• To add an exclusion criterion for participants weighing under 15 kilograms (kg) and receiving maintenance IVIg.
• To revise the SoAs for PK, hemolysis, and free C5 testing and to add clinical laboratory testing at 6 months intervals during the extension phase.
• To enhance clarity of guidance around collection of AEs throughout the protocol to clarify that all AEs (serious and non-serious) were to be collected from the signing of the informed consent form (ICF).
• To update the PK/PD sampling window times.
• To clarify that the overall duration of study drug administration should not exceed 4 hours from the start of infusion in participants aged ≥18 years receiving maintenance IVIg.
• To enhance clarity of guidance around adjustment of immunosuppressant therapies (ISTs) during the study.
• To add subcutaneous immunoglobulin (Ig) under disallowed medications.
• To remove pulse oximetry from vital sign assessments.
• To enhance clarity around the process for reporting serious adverse events (SAEs). |
||
28 Sep 2020 |
The purpose of this global amendment was:
• To increase the maximum number of participants aged 12 to <18 years who may enter the study on maintenance IVIg from 4 to 6.
• To add text regarding the protection of participant data
• To revise the SoAs to include study drug infusion at the End of Study Visit for the Primary Evaluation Treatment Period and throughout the 208-week Extension Period. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
