Clinical Trial Results:
A prospective, randomized, open-label, interventional study to investigate the efficacy of complement C5 inhibition with Zilucoplan® in improving oxygenation and short- and long-term outcome of COVID-19 patients with acute hypoxic respiratory failure.
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Summary
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EudraCT number |
2020-002130-33 |
Trial protocol |
BE |
Global end of trial date |
09 Apr 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Jun 2022
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First version publication date |
04 Jun 2022
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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 |
ZILU-COV
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04382755 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
UZ Gent
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Sponsor organisation address |
C. Heymanlaan 10, Ghent, Belgium, 9000
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Public contact |
HIRUZ CTU, University Hospital Ghent, +32 93320500, hiruz.ctu@uzgent.be
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Scientific contact |
HIRUZ CTU, University Hospital Ghent, 093322352 93320500, hiruz.ctu@uzgent.be
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
12 Oct 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
29 Dec 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Apr 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this intervention is to study if Zilucoplan® affects the the median and/or mean change in oxygenation between enrolment (baseline) and at predose day 6 and day 15 (or discharge, whichever comes first) through assessment of the PaO2/FiO2 ratio and through measurement of the P(A-a)O2 gradient, which can easily be performed in the setting of clinical observation of patients admitted to the COVID-19 ward or ICU COVID-19 unit. For patients on ECMO the PaO2/FiO2 ratio and Aa-gradient cannot be calculated as in this case the FiO2 will be missing. Therefore, the last available value of PaO2/FiO2 ratio and Aa gradient prior to ECMO can be used at that timepoint.
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Protection of trial subjects |
Ethics review and approval, informed consent, supportive care and routine monitoring, data protection in accordance with law on General Data Protection Regulation (GDPR) and institutional rules [Belgian law dated on 30 July 2018 and 22 Aug. 2002], insurance.
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Background therapy |
All patients will receive standard of Care (SoC). Due to the rapidly evolving scientific insights, SoC for Covid-19 was not further defined a priori. Prophylaxis against meningococcal disease will be given in the active group A receiving zilucoplan, in the form of antibiotic prophylaxis with a third generation cephalosporin or alternative covering N. menigitidis and S. pneumoniae in case of allergies or clinical indication. A antibiotic is administered until at least 14 days after the last dose of zilucoplan in group A. Group B patients will receive a daily injection of 2g ceftriaxone IV or appropriate alternative in case of allergies or on clinical indication, during one week or until hospital discharge, whichever comes first. | ||
Evidence for comparator |
Treatment with the approved C5 inhibitors eculizumab and ravulizumab, as well as rare genetic deficiencies in C5, are associated with a markedly increased risk for infection with encapsulated bacteria, most notably Neisseria meningitidis and H. influenzae, but not for viral infections generally, or for coronavirus infections in particular. To prevent the risk of meningococcal disease and prevent other infections with encapsulated bacteria, patients in the active group A will receive prophylactic antibiotics. To control for the effects of antibiotic prophylaxis against menigococcal disease on clinical course of COVID-19, the control group B will also receive 1 week (or until hospital discharge whichever comes first) of IV 3rd generation cephalosporin. In case of allergies to these antibiotics, or on clinical indication, these antibiotics may be switched to antibiotics that also cover Neisseria meningitidis. | ||
Actual start date of recruitment |
22 May 2020
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy, Scientific research | ||
Long term follow-up duration |
5 Months | ||
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 |
Belgium: 81
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Worldwide total number of subjects |
81
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EEA total number of subjects |
81
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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) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
42
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From 65 to 84 years |
38
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85 years and over |
1
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Recruitment
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Recruitment details |
84 patients were assessed for eligibility and 81 patients were randomized in the period from 15-aug-2020 till 16-dec-2021. 78 patients were included in the safety and primary analysis. End of trial notification was dated 27-may-2021 (last patient last visit) and submitted to EC and CA 30-jul-2021. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Confirmed COVID-19 patients between the age of 18 and 80 years were screened for acute hypoxic respiratory failure (saturation <93% on minimal 2 L/min O2 or PaO2/FiO2 <350). Invasive mechanical ventilation >24h, history of severe allergic reactions and unlikely to servive beyond 48h were the most important exclusion criteria. | ||||||||||||||||||
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Period 1
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Period 1 title |
Randomized Set
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Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
Blinding implementation details |
N.A.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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arm A (Zilucoplan + SoC) | ||||||||||||||||||
Arm description |
standard of care + 32.4 mg Zilucoplan SC once daily for 14 days or until discharge, whichever comes first + daily prophylactic 3d generation cephalosporin IV for 14 days or untill discharge whichever comes first. After last Zilucoplan dose : - Patient still hospitalized: continue daily prophylactic 3d generation cephalosporin IV until 14 days after last Zilucoplan dose. - Patient discharged: prophylactic oral ciprofloxacin 500mg daily until 14 days after last Zilucoplan dose. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Zilucoplan
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Investigational drug product will be provided in prefilled syringes containing 32.4 mg of Zilucoplan® for subcutaneous injection in the abdomen (preferred site), thigh, or upper arm. This dose is equivalent to that administered to the highest weight bracket in prior weight-based dosing regimens and is expected to achieve rapid, profound, and sustained complement inhibition with acceptable safety and tolerability.
Subjects who present with very low body weight (<54kg) are excluded from enrolment. Subjects with very high body weight (>150 kg) are also excluded.
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Investigational medicinal product name |
ceftriaxone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for emulsion for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
daily IV infusion of 2g of ceftriaxone until hospital discharge (or until 28 days after randomization when still in hospital, whichever comes first). If patient is discharged before day 28 after randomization, patient will switch to oral ciprofloxacin 1x500 mg per day until at least 14 days after the last Zilucoplan® administration.
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Arm title
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Arm B (SoC) | ||||||||||||||||||
Arm description |
Group B patients will receive daily IV infusion of 2g of ceftriaxone daily IV during one week or until hospital discharge, whichever comes first. In case of unavailability, ceftriaxone can be replaced by cefotaxime 1g every 8 hours. | ||||||||||||||||||
Arm type |
prophylactic antibiotics | ||||||||||||||||||
Investigational medicinal product name |
ceftriaxone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for emulsion for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Daily IV infusion of 2g of ceftriaxone daily IV during one week or until hospital discharge, whichever comes first. In case of allergies or on clinical grounds, prophylaxis with ceftriaxone could be changed to another antibiotic also providing coverage for N. meningitidis and S. pneumoniae.
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Period 2
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Period 2 title |
Full Analysis Set
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Is this the baseline period? |
Yes [1] | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Arm A (Zilucoplan + Soc) | ||||||||||||||||||
Arm description |
standard of care + 32.4 mg Zilucoplan SC once daily for 14 days or until discharge, whichever comes first + daily prophylactic 3rd generation cephalosporin IV for 14 days or until discharge whichever comes first. After kast Zilucoplan dose: - Patients still hospitalized: continue daily prophylactic 3rd generation cephalosporin IV until 14 days after last Zilucoplan dose. - Patient discharged: prophylactic oral ciprofloxacin 500 mg daily until 14 days after last Zilucoplan dose. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Zilucoplan
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Investigational drug product will be provided in prefilled syringes containing 32.4 mg of Zilucoplan® for subcutaneous injection in the abdomen (preferred site), thigh, or upper arm. This dose is equivalent to that administered to the highest weight bracket in prior weight-based dosing regimens and is expected to achieve rapid, profound, and sustained complement inhibition with acceptable safety and tolerability.
Subjects who present with very low body weight (<54kg) are excluded from enrolment. Subjects with very high body weight (>150 kg) are also excluded.
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Investigational medicinal product name |
ceftriaxone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for emulsion for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
daily IV infusion of 2g of ceftriaxone until hospital discharge (or until 28 days after randomization when still in hospital, whichever comes first). If patient is discharged before day 28 after randomization, patient will switch to oral ciprofloxacin 1x500 mg per day until at least 14 days after the last Zilucoplan® administration.
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Arm title
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Arm B (SoC) | ||||||||||||||||||
Arm description |
Group B patients will receive daily IV infusion of 2g of ceftriaxone daily IV during one week or until hospital discharge, whichever comes first. In case of unavailability, ceftriaxone can be replaced by cefotaxime 1 g every 8 hours. | ||||||||||||||||||
Arm type |
prophylactic antibiotics | ||||||||||||||||||
Investigational medicinal product name |
ceftriaxone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for emulsion for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Daily IV infusion of 2g of ceftriaxone daily IV during one week or until hospital discharge, whichever comes first. In case of allergies or on clinical grounds, prophylaxis with ceftriaxone could be changed to another antibiotic also providing coverage for N. meningitidis and S. pneumoniae.
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| Notes [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period. Justification: Period 1 is the Randomized Set. This set includes 3 patients of whom we did not collect any data, but who were randomized. Period 2 is the Full Analysis Set (without the aforementioned 3 patients). Therefore, this set is used as baseline period. |
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| Notes [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Three patients were randomized, but did not meet inclusion criteria or withdrew consent prior to first drug administration. Hence, no data of these patients are collected. |
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Baseline characteristics reporting groups
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Reporting group title |
Arm A (Zilucoplan + Soc)
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Reporting group description |
standard of care + 32.4 mg Zilucoplan SC once daily for 14 days or until discharge, whichever comes first + daily prophylactic 3rd generation cephalosporin IV for 14 days or until discharge whichever comes first. After kast Zilucoplan dose: - Patients still hospitalized: continue daily prophylactic 3rd generation cephalosporin IV until 14 days after last Zilucoplan dose. - Patient discharged: prophylactic oral ciprofloxacin 500 mg daily until 14 days after last Zilucoplan dose. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm B (SoC)
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Reporting group description |
Group B patients will receive daily IV infusion of 2g of ceftriaxone daily IV during one week or until hospital discharge, whichever comes first. In case of unavailability, ceftriaxone can be replaced by cefotaxime 1 g every 8 hours. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
arm A (Zilucoplan + SoC)
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Reporting group description |
standard of care + 32.4 mg Zilucoplan SC once daily for 14 days or until discharge, whichever comes first + daily prophylactic 3d generation cephalosporin IV for 14 days or untill discharge whichever comes first. After last Zilucoplan dose : - Patient still hospitalized: continue daily prophylactic 3d generation cephalosporin IV until 14 days after last Zilucoplan dose. - Patient discharged: prophylactic oral ciprofloxacin 500mg daily until 14 days after last Zilucoplan dose. | ||
Reporting group title |
Arm B (SoC)
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Reporting group description |
Group B patients will receive daily IV infusion of 2g of ceftriaxone daily IV during one week or until hospital discharge, whichever comes first. In case of unavailability, ceftriaxone can be replaced by cefotaxime 1g every 8 hours. | ||
Reporting group title |
Arm A (Zilucoplan + Soc)
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Reporting group description |
standard of care + 32.4 mg Zilucoplan SC once daily for 14 days or until discharge, whichever comes first + daily prophylactic 3rd generation cephalosporin IV for 14 days or until discharge whichever comes first. After kast Zilucoplan dose: - Patients still hospitalized: continue daily prophylactic 3rd generation cephalosporin IV until 14 days after last Zilucoplan dose. - Patient discharged: prophylactic oral ciprofloxacin 500 mg daily until 14 days after last Zilucoplan dose. | ||
Reporting group title |
Arm B (SoC)
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Reporting group description |
Group B patients will receive daily IV infusion of 2g of ceftriaxone daily IV during one week or until hospital discharge, whichever comes first. In case of unavailability, ceftriaxone can be replaced by cefotaxime 1 g every 8 hours. | ||
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End point title |
LSMean change from baseline in PaO2/FiO2 | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 6
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Statistical analysis title |
P-value | ||||||||||||
Comparison groups |
arm A (Zilucoplan + SoC) v Arm B (SoC)
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Number of subjects included in analysis |
72
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.12 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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End point title |
LSMean change from baseline in PaO2/FiO2 | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 15
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Statistical analysis title |
P-value | ||||||||||||
Comparison groups |
arm A (Zilucoplan + SoC) v Arm B (SoC)
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Number of subjects included in analysis |
60
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.14 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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End point title |
LSMean change from baseline in a/A PO2 | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 6
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Statistical analysis title |
P-value | ||||||||||||
Comparison groups |
arm A (Zilucoplan + SoC) v Arm B (SoC)
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Number of subjects included in analysis |
72
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.15 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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End point title |
LSMean change from baseline in a/A PO2 | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 15
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Statistical analysis title |
P-value | ||||||||||||
Comparison groups |
arm A (Zilucoplan + SoC) v Arm B (SoC)
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Number of subjects included in analysis |
60
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.14 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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End point title |
Geometric LSMean (A-a) gradient | ||||||||||||
End point description |
Geometric LSMean
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End point type |
Primary
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End point timeframe |
Day 6
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Statistical analysis title |
P-value | ||||||||||||
Comparison groups |
arm A (Zilucoplan + SoC) v Arm B (SoC)
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Number of subjects included in analysis |
68
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.22 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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End point title |
Geometric LSMean (A-a) gradient | ||||||||||||
End point description |
Geometric LSMean
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End point type |
Primary
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End point timeframe |
Day 15
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Statistical analysis title |
P-value | ||||||||||||
Comparison groups |
arm A (Zilucoplan + SoC) v Arm B (SoC)
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Number of subjects included in analysis |
56
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.11 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
screening and during 28 day assessment period.
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
5.0
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Reporting groups
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Reporting group title |
Arm A (Zilucoplan + SoC)
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Reporting group description |
standard of care + 32.4mg Zilucoplan SC once daily for 14 days or until discharge, whichever comes first + daily prophylactic 3d generation cephalosporin IV for 14 days or until dicharge, wichever comes first. After last Zilucoplan dose: - patient still hospitalized: Continue daily prophylactic 3d generation cephalosporin IV untill 14 days after last Zilucoplan dose. - patient discharged: prophylactic oral ciprofloxacin 500mg daily until 14 days after last Zilucoplan dose. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm B (SoC)
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Reporting group description |
standard of care + daily prophylactic 3d generation cephalosporin IV for 7 days or until discharge, whichever comes first. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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29 May 2020 |
Section 2.1: study design added.
Section 7.1.2: wording changed to “An Investigator must discontinue or withdraw a subject from the study for the following reason.”
Clarification added on prophylaxis for meningococcal disease
Section 9.2, 9.4: Follow up visit week 12-22 after randomization: additional assessments were added: WHO performance scale, 6 minutes walk test (per standard of care), HRCT scan to evaluate HRCT fibrosis score
Section 9.4: assessment of vital signs: values to be collected at morning assessment, between 7-10 AM for all parameters. 6-point ordinal scale: scoring updated to "1=Death”. HRCT fibrosis score: instructions on how to score HRCT findings.
Section 13.5: text added: A careful assessment will be performed in cases where disease related events appear to be enhanced by the IMP. In accordance with CT-3 guidance, a causality assessment will be performed for each SAE, and if the investigator considers disease related event to be IMP-related and the event is serious,related and unexpected, then it will be reported as a SUSAR.
Section 13.6: Additional information on DSMB Charter
Section 9.3, 9.4, 10: details on samples to be collected updated, cfr. updated lab manual provided by central lab, Covance
Section 12.1.2 information added that no data will be collected directly into the eCRF.
Section 11.1: primary endpoint changed to day 6, day 15 (or discharge).
Section 6.1: information added on anti-conception requirements for male subjects.
Section 4.2: definition of ARDS changed according to the Berlin criteria according to Jason Chertoff.
Section 1., 5.1: definition of Hypoxic respiratory failure changed. |
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10 Jun 2020 |
Section 1., 3.2, 4.2: secondary objectives changed.
Section 3.1 and 4.1 Clarification for ECMO patients added.
Section 4.2: Definition of ARDS: bullet point 4 changed.
Section 6.1: Definition hypoxia changed.
Section 9.2, 9.4:
- laboratory assessments removed (fibrinogen and triglycerides at Day 6, 15 and FU)
- Score assessments removed: Clinical Sign Score, Glasgow Come Scale and NEWS2. HScore only at Day 1.
- Information added on timing of evaluation of 6 point ordinal scale and HScore.6 minute walk test: protocol requirement, not following SOC.
Section 9.3:
- Listing of lab assessments removed.
- Day 4 was changed into day 6
Timepoint of analysis of cytokines changed from Day 14 to Day 15.
General: typo’s corrected.
Section 10: D1: samples of 5ml for PK was changed into 6 ml. One 6 ml EDTA tube was added for complement (according to flowchart).
Section 13.4: in flowchart reporting , ‘HIRUZ CTU will inform all participating sites’ was added for SUSARs
Section 9.2: clinical exam and ECG added to section “at screening”, to correspond with 9.4. |
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10 Jul 2020 |
Section 3.1 and 5.1 and 7.1 and 9.4: statement/clarification on use of alternative antibiotics in case of allergy to cephalosporin or ciprofloxacin
Section 6.2: Exclusion Criteria added: patient on ECMO at screening
Section 8.1.4: clarification added on administration of IMP during 24 hours dialysis.
Section 9.4: Physical Examination: to be assessed on clinical grounds, as per standard of care. Clarification for ECMO patients added |
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09 Apr 2021 |
Section 4.2: Typo “≥60” corrected to “≥ 50”.
Section 4.2: Secondary endpoints updated according to SAP
Section 4.3 has been added and describes the pharmacodynamics and pharmacokinetic endpoints
Section 7.3, 9.4: information added on assessment of arterial blood gas: if an arterial blood gas value is available of less than 24 hours before randomization, there’s no need to have a new ABG done on Day 0/1.
Section 9.4: correction in footnote: time window of assessment of vital signs is not applicable for the follow-up visit.
Section 13.3: Reporting address for SAEs changed to DS_ICT@ucb.com
Section 13.7: clarification added on timelines of submission of DSUR.
Section 10.3, 10.4: clarification added on analysis and storage by selected centres of optional samples.
Section 10.5: identification of FAGG certified biobank to store remaining samples for future use.
Section 9.2: volume of DNA EDTA changed from 5 ml to 4 ml (typo).
Section 11.0: Update of statistical analysis team
Section 5.1: “Group B” removed from sentence about prophylactic antibiotic treatment for patient randomized to Group A.
*Amendment was approved by the regulatory authority on 27-Apr-2021* |
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09 Apr 2021 |
Section 4.2 : All secondary endpoints not related to secondary objectives have been moved to new section 4.3 “exploratory endpoints” section.
Duplicates within secondary endpoint section have been removed.
Removal of analytical language e.g. ‘means’ has been updated to reflect the endpoint itself not the analytical approach
Section 4.3 Exploratory Endpoints was added. The content of this section concerns endpoints previously listed under section 4.2 which have been moved to the current section
4.3. For some of the endpoints, analytical language e.g. ‘means’ has been updated to reflect the endpoint itself not the analytical approach
Section 4.4: clarification was added related to the exploratory nature of pharmacodynamic and pharmacokinetic endpoints
Section 4.4: aPTT and PT have been removed from Pharmacodynamic endpoints
Section 11.1 : name of individual UCB statistician Trevor Smart replaced by UCB
Section 11.2: Clarification was added regarding the endpoints to be summarized.
Section 11.2: the sentence “Data from SOC in another study with a very similar protocol will be incorporated into the analysis using a Bayesian frame work. This will be described more fully in the statistical analysis plan (SAP).”
Has been replaced by “Data from SOC in another study with a very similar protocol may be incorporated into the analysis using a Bayesian frame work. This will be described more fully in the statistical analysis plan (SAP).”
Section 12.4: The sentence “Pseudonymized biological analyses and study results will also be shared with the provider of Zilucoplan® (UCB Pharma)” has been replaced by “Pseudonymized biological analyses, study data and study results will also be shared with the provider of Zilucoplan® (UCB Pharma) “
*Amendment was approved by the regulatory authority on 09-June-2021* |
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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. | |||
| 1) open label design 2) 14 days of prophylactic antibiotics in Zilucoplan group vs 7 days in SoC 3) population predominantly composed of white men 4) FiO2 based on the method of oxygen delivery and flow 5) differences in baseline characteristics | |||
