Primary ObjectiveTo determine if the humoral immune response of a single compared to a two dose COVID-19 vaccination regimen is non-inferior in paediatric subjects who are immunologically primed by natural infection. Secondary Objective(s) 1.To…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The geometric mean ratio of neutralizing titers against wild type virus (Virus
Neutralization Assay) at day 28 after completion of the control versus the
intervention regimen of the vaccine.
Secondary outcome
Safety:
-The percentage of subjects reporting at least one solicited systemic adverse
events Grade >= 2 (AEs) in the 7 days after any vaccine dose, as measure of
systemic reactogenicity.
-The percentage of subjects reporting solicited local and systemic adverse
events (AEs) for 7 days after each vaccine dose.
-The percentage of subjects reporting unsolicited AEs for 14 days after each
vaccine dose.
-The percentage of subjects reporting serious adverse events (SAEs) Grade >=3 on
the Common Toxicity Criteria or Adverse Events of Special interest (AESI) until
12 months post-vaccination.
Immunogenicity:
-Neutralizing titers against wild type virus (Virus Neutralization Assay) at 6
and 12 months post-vaccination.
-Quantitative enzyme-linked immunosorbent assay (anti-RBD-ELISA) at 28 days, 6
months and 12 months post-vaccination.
-Geometric Mean Fold Ratio in SARS-CoV-2 serum anti-RBD antibody titer from
before vaccination to each subsequent time points at 1, 6 and 12 months
post-vaccination.
-Neutralizing titers against variants of concern (Virus Neutralization Assay)
at day 28 and 6 months post-vaccination.
Background summary
Since early in the pandemic, it has been evident that the disease severity and
transmissibility from SARS-CoV-2 infection in children and adolescents are
reduced compared to adults. Yet paediatric hospitalisations and deaths do
occur, in particular in subjects without any prior immunity to the virus and
when virus circulation in the community is high. SARS-CoV-2 infections in
children and adolescents may also serve as a reservoir of the virus, thereby
maintaining community transmission and fuelling the emergence of new mutant
strains. The role of children in the spread of COVID-19 seems to be affected by
different contact patterns and hygienic habits, so that more intense contact
and mixing patterns, for example in schools, could offset the effect of reduced
susceptibility and infectivity. As children have been *last in line* - if at
all included- in vaccination programs across Europe and globally, an increasing
fraction of vaccine eligible children will consist of non- naïve individuals.
In combination with the emerge of the rapidly spreading Omicron variant in
early 2022, it is estimated that the vast majority of the population has
experienced a SARS-CoV-2 infection at some point. This ensures that almost
every child who will receive a corona vaccination in the future has already
been in contact with the virus.
Evidence from adult clinical studies reveals that in individuals with a
previous SARS*CoV*2 infection, a single dose of messenger RNA (mRNA) vaccine is
immunologically equivalent, or even superior, to a full vaccine schedule in
naïve individuals. These observations demonstrate that the first vaccine dose
serves as a booster in naturally infected adult individuals and therefore it is
sufficient to administer just a single dose as the primary vaccine series. As a
result, European countries have adopted a single*dose primary series mRNA
vaccine strategy for adolescents and adults with evidence of prior SARS*CoV*2
infection. However, although some countries recommend a single dose as
vaccination regime for children 5-11 years with prior SARS*CoV*2, a single dose
is not indicated in the current SmPC due to lack of data.
From theory however, it is most plausible that a similar approach could be used
in children 5*11 years old with prior infection. A single dose primary series
would have several advantages over a two*dose approach for several reasons.
First, it reduces the burden of injections and side effects in children.
Second, it lowers the risk of rare side effects such as myocarditis due to
immune hyperstimulation. Third, it supports and overall dose sparing strategy.
Fourth, it may reduce the risk of original antigenic sin due to repeated
selective stimulation of the immune response to the vaccine type of SARS*CoV*2.
This could be of particular importance in light of the partial immune escape
seen with emerging variants of concern (VoCs). Since the Omicron variant became
dominant, the risk of developing severe COVID-19 from a SARS-CoV-2 infection is
now low for most children aged 5 to 11. The risk is higher for children with
serious underlying medical conditions. For this reason, most European countries
have now adjusted their vaccination advice for children aged 5-11 years of age,
so that vaccination is only offered to children with an increased medical risk.
Study objective
Primary Objective
To determine if the humoral immune response of a single compared to a two dose
COVID-19 vaccination regimen is non-inferior in paediatric subjects who are
immunologically primed by natural infection.
Secondary Objective(s)
1.To assess the safety and reactogenicity profile of a single dose COVID-19
vaccine regimen against SARS-CoV-2 in paediatric subjects with a history of
prior SARS-CoV-2 infection, compared to the two dose regimen.
2.To assess the medium (6 months) and long term (12 month) humoral immune
response of the single COVID-19 vaccine dosing regimen against wild-type
SARS-CoV-2 in paediatric subjects with a history of prior SARS-CoV-2 infection.
3.To assess the short (28 days), medium and long term humoral immune response
of the single dose COVID-19 vaccine regimen against SARS-CoV-2 variants of
concern (VoCs) in paediatric subjects with a history of prior SARS-CoV-2
infection.
Study design
The design is a comparative randomised Phase 2 study in healthy children to
evaluate immunogenicity and safety profiles of a single dose COVID-19 mRNA
vaccination regimen in paediatric subjects with prior SARS-CoV-2 infection.
The protocol will have two arms. The population consists of paediatric subjects
with documented evidence of prior SARS-CoV-2 infection. Subjects will be
randomised to receive either 1) BNT162b2 first dose followed by a second
BNT162b2 dose (control arm), or 2) a single dose of BNT162b2 vaccine
(intervention arm). The subjects will be fully vaccinated with either the 10 µg
Original Comirnay or the 5/5 µg Comirnaty Original/Omicron BA.4-5.
Randomisation will be stratified by sex and centre.
Intervention
The protocol will have two arms. Subjects will be randomised to receive either
1) BNT162b2 first dose followed by a second BNT162b2 dose (control arm), or 2)
a single dose of BNT162b2 vaccine (intervention arm). The subjects will be
fully vaccinated with either the 10 µg Original Comirnay or the 5/5 µg
Comirnaty Original/Omicron BA.4-5.
Randomisation will be stratified by sex and centre.
Study burden and risks
Participation in this clinical trial poses a minimal risk of inconvenience
through sample collection and attendance of follow-up visits. Furthermore the
Investigational Product is already registered for the study population.
Therefore, subjects volunteering for this trial are not considered to be at
additional risk in relation with the authorized standard of care vaccine
administration. There is a very small risk that a single dose regimen is less
effective against severe COVID-19. However, even without vaccination the risk
of severe COVID-19 is already extremely low in this age group, such that any
small effect on efficacy would have minimal or no health consequences. Benefits
for the subjects in the intervention group are related to potential achievement
of immunogenicity while providing lower reactogenicity in this group receiving
a single dose.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
1.Aged >=5 years to <=11 years of age on day of signing the informed consent form.
2.In good health or stable clinical condition.
3.Legally Acceptable Representative (LAR) has reviewed the subject information
and signed the informed consent form on behalf of the subject and the subject
has expressed willingness to participate.
Exclusion criteria
1.Has previously received any investigational or licensed COVID-19 vaccine.
2. Has known congenital or acquired immune disorder or immunodeficiency that
may interfere with vaccine response e.g. known infection with human
immunodeficiency virus (HIV) with low CD4 count or other immunosuppression at
time of signing informed consent form.
3. Has a history of autoimmune disease or an active autoimmune disease
requiring therapeutic intervention (including systemic glucocorticoids), or
findings that may have a significant effect on the target endpoints and which
may therefore mask or inhibit the therapeutic effect under investigation as
judged by the investigator.
4. Bleeding diathesis or condition associated with prolonged bleeding that
would, in the opinion of the investigator, contraindicate intramuscular
injection or venepuncture.
5. History of severe adverse reaction associated with a vaccine and/or severe
allergic reaction (eg, anaphylaxis) to any component of the study
intervention(s).
6. Receipt of medications intended to prevent COVID-19.
7. Uses drugs with significant interaction with the investigational product or
has any contraindications as per the Summary of Product Characteristics.
8. Other medical or psychiatric condition or laboratory abnormality that may
increase the risk of study participation or, in the investigator*s judgment,
make the subject inappropriate for the study.
9. Has any kind of dependency on the principal investigator or member of the
study team or LAR is employed by the principal investigator or within the same
department as the PI or study team at the institution where the study is
executed.
10. Is unable to report solicited adverse events.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-005043-71-NL |
| CCMO | NL79226.000.21 |