Clinical Trial Results:
A Phase 2, Comparative Randomised Trial to Evaluate the impact of reduced COVID-19 mRNA vaccination regimens on immunological responses and reactogenicity in paediatric subjects with and without prior SARS-CoV-2 infection (CoVacc)
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Summary
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EudraCT number |
2021-005043-71 |
Trial protocol |
NL NO DE SE GR |
Global end of trial date |
06 May 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Nov 2024
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First version publication date |
22 Nov 2024
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Other versions |
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Summary report(s) |
CoVacc Summary Clinical Study Report |
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 |
EU-COVPT-1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University Medical Center Utrecht
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Sponsor organisation address |
Heidelberglaan 100, Utrecht, Netherlands, 3584 CX Utrecht
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Public contact |
Patricia Bruijning-Verhagen, University Medical Center Utrecht, p.bruijning@umcutrecht.nl
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Scientific contact |
Patricia Bruijning-Verhagen, University Medical Center Utrecht, p.bruijning@umcutrecht.nl
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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 |
15 Aug 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 May 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
06 May 2024
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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 |
To determine if the humoral immune response of a fractional compared to a full dose COVID‐19 vaccination is non‐inferior in paediatric subjects who are immunologically primed either by a first vaccine dose, or by natural infection.
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Protection of trial subjects |
All legally authorized representatives provided extensive information about the trial in the subject information sheet and subsequently provided informed consent. In addition, in several countries an additional subject information sheet (and informed consent) was provided for certain age groups of the children.
In addition, as little visits as possible are implemented, with as little as possible blood sampling to reduce subject burden, while still being able to address the research objective. Furthermore, some study sites offered subjects the option of a numbing cream to lessen the feeling of the blood draw.
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Background therapy |
N/a | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
31 May 2022
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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 |
Netherlands: 23
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Country: Number of subjects enrolled |
Norway: 5
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Country: Number of subjects enrolled |
Sweden: 3
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Worldwide total number of subjects |
31
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EEA total number of subjects |
31
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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) |
31
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Adolescents (12-17 years) |
0
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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 |
From 31-May-2022 to 9-Jan-2024, a total of 31 subjects across 3 countries (NL, NO, SE) were enrolled and randomly assigned in the trial. | |||||||||
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Pre-assignment
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Screening details |
Subjects were screened using the eligibility criteria of the protocol. | |||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
Blinding implementation details |
No blinding.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Two dose arm | |||||||||
Arm description |
Two doses of Comirnaty 10 μg or Comirnaty Original/Omicron BA.4-5 5/5 μg or Comirnaty Omicron XBB.1.5 10 μg, with an interval of 3-12 weeks (preferably 8 weeks) as per local standard practise. | |||||||||
Arm type |
Control | |||||||||
Investigational medicinal product name |
Comirnaty
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Investigational medicinal product code |
J07BN013
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Other name |
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Pharmaceutical forms |
Concentrate for dispersion for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Comirnaty 10 μg or Comirnaty Original/Omicron BA.4-5 5/5 μg or Comirnaty Omicron XBB.1.5 10 μg first dose followed by a second Comirnaty 10 μg or Comirnaty Original/Omicron BA.4-5 5/5 μg or Comirnaty Omicron XBB.1.5 10 μg dose. The first and second dose of the vaccine should be the same.
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Arm title
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Single dose arm | |||||||||
Arm description |
A single Comirnaty 10μg dose or Comirnaty Original/Omicron BA.4-5 5/5 μg or Comirnaty Omicron XBB.1.5 10 μg dose | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Comirnaty
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Investigational medicinal product code |
J07BN013
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Other name |
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Pharmaceutical forms |
Concentrate for dispersion for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
A single Comirnaty 10 μg or Comirnaty Original/Omicron BA.4-5 5/5 μg or Comirnaty Omicron XBB.1.5 10 μg dose.
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Baseline characteristics reporting groups
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Reporting group title |
Two dose arm
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Reporting group description |
Two doses of Comirnaty 10 μg or Comirnaty Original/Omicron BA.4-5 5/5 μg or Comirnaty Omicron XBB.1.5 10 μg, with an interval of 3-12 weeks (preferably 8 weeks) as per local standard practise. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Single dose arm
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Reporting group description |
A single Comirnaty 10μg dose or Comirnaty Original/Omicron BA.4-5 5/5 μg or Comirnaty Omicron XBB.1.5 10 μg dose | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
PP - primary endpoint
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All subjects who received a study vaccine and contributed both pre- and at least one post-vaccination blood sample for immunogenicity testing for which valid results were reported, but excluding subjects found to be ineligible at baseline, subjects who have had a confirmed new SARS infection between baseline and the visit concerned, subjects with major protocol deviations that are considered to affect the outcome, data from any visits that occurred substantially out of the foreseen time window.
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Subject analysis set title |
mITT primary endpoint
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Subject analysis set type |
Modified intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All trial subjects who received a study vaccine and contributed both pre- and at least one post-vaccination blood sample for immunogenicity testing for which valid results were reported.
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End points reporting groups
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Reporting group title |
Two dose arm
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Reporting group description |
Two doses of Comirnaty 10 μg or Comirnaty Original/Omicron BA.4-5 5/5 μg or Comirnaty Omicron XBB.1.5 10 μg, with an interval of 3-12 weeks (preferably 8 weeks) as per local standard practise. | ||
Reporting group title |
Single dose arm
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Reporting group description |
A single Comirnaty 10μg dose or Comirnaty Original/Omicron BA.4-5 5/5 μg or Comirnaty Omicron XBB.1.5 10 μg dose | ||
Subject analysis set title |
PP - primary endpoint
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All subjects who received a study vaccine and contributed both pre- and at least one post-vaccination blood sample for immunogenicity testing for which valid results were reported, but excluding subjects found to be ineligible at baseline, subjects who have had a confirmed new SARS infection between baseline and the visit concerned, subjects with major protocol deviations that are considered to affect the outcome, data from any visits that occurred substantially out of the foreseen time window.
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Subject analysis set title |
mITT primary endpoint
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
All trial subjects who received a study vaccine and contributed both pre- and at least one post-vaccination blood sample for immunogenicity testing for which valid results were reported.
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End point title |
The geometric mean ratio of neutralising titers against wild type virus (Virus Neutralization Assay) at day 28 after completion of the control versus the intervention regimen of the vaccine | ||||||||||||
End point description |
The primary analysis of this study was the non-inferiority comparison of the primary endpoint between the control and intervention arm in the per protocol (PP) population. A linear model with the
log10 transformed SARS-CoV-2 neutralizing titers as dependent variable and with independent variables treatment group, log10 transformed baseline titers and the variables used for stratification
(sex) was planned to fit. Based on the linear model estimates for the factor treatment group, the null hypothesis that the intervention group is inferior to the standard two dose BNT162b2 vaccination regimen was tested. Non-inferiority was defined as a 1.5-fold difference for GMTs or 0.176 on the log scale (base 10). Based on the linear model 2-sided 95% confidence intervals for the fold difference in GMT were computed. If the 95% confidence interval for the difference excludes 0, inferiority / superiority was concluded. One sided p- values for the inferiority null hypothesis were reported.
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End point type |
Primary
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End point timeframe |
28 days
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Statistical analysis title |
Primary analysis | ||||||||||||
Comparison groups |
Two dose arm v Single dose arm
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
Method |
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Parameter type |
GMT ratio | ||||||||||||
Point estimate |
0.942
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Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
0.554 | ||||||||||||
upper limit |
1.601 | ||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline to end of study visit
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Adverse event reporting additional description |
All adverse events reported spontaneously by the subject or observed by the investigator or his staff were recorded.
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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 |
25.1
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Reporting groups
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Reporting group title |
two dose arm
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Reporting group description |
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Reporting group title |
Single dose arm
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Reporting group description |
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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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27 Oct 2021 |
Substantial amendment to address questions and comments from EC/CA review, regarding e.g. emergency unblinding, end of trial definition, and DMC process. |
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19 Jan 2022 |
Changes were made throughout the protocol, including protocol title, summary, section 1 Introduction and Rationale (including section 14 references to most recent clinical trials), section 2 Objectives and section 3 Study Design, to reflect updated study design and study population:
• Replace Cohort A (SARS-CoV-2 naïve adolescents of 12 and 13 years) and Cohort B (adolescents of 12 and 13 years with documented evidence of prior SARS-CoV-2 infection) with a subject population of children 5 up to and including 11 years with documented evidence of prior SARS-CoV-2 infection;
• Randomization into two arms: 1) a 10 μg BNT162b2 first dose followed by a second 10μg BNT162b2 dose, or 2) a single 10μg dose of BNT162b2 vaccine. |
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17 Mar 2022 |
Main changes included a clarification of the exclusion criteria, updated study timelines and updated visit schedule (incl removal of a visit in the single dose arm) |
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24 Mar 2023 |
The main changes included the addition of the Comirnaty bi-valent paediatric vaccine as study medication and removal of the inclusion criterion that required documented evidence of prior SARS-CoV-2 infection,. |
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22 Sep 2023 |
The main change included the addition of the Comirnaty Omicron XBB vaccine as study medication. |
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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. | |||
| Only 31 of the targeted 200 subjects were included by the end of the trial. | |||
