To assess the antibody response after SARS-CoV-2 vaccination in people >=16 years and children with Down Syndrome. Part 2To assess the antibody response after a third SARS-CoV-2 vaccination in adults and children with Down Syndrome and to compare…
ID
Source
Brief title
Condition
- Other condition
- Immune disorders NEC
- Viral infectious disorders
Synonym
Health condition
Down syndroom
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the serum concentration of SARS-CoV-2-specific
antibodies (against the spike protein) at t=3 (on day 28 after the second
vaccination) as measured by the multiplex immune assay (MIA) by the National
Institute for Public Health and the Environment (RIVM). Participants will be
classified as responders or non-responders. The definition of response will be
based on the latest available data from the pivotal studies and will be defined
prior to data analyses and the first database lock. We will inform the IRB
about this definition and add this information to ClinicalTrials.gov. The
percentage of responders in the Down Syndrome versus the healthy controls will
be compared.
Part 2
The primary endpoint of the second part of the study is the serum concentration
of SARS-CoV-2-specific antibodies (against the spike protein) at t=5 (on day
28 after the third vaccination) as measured by the multiplex immune assay (MIA)
by the National Institute for Public Health and the Environment (RIVM).
Secondary outcome
Secondary endpoints include:
- longevity of the immune response at 6 months after the last vaccination and 1
to 1,5 years after the intitial vaccination series.
- mucosal antibody response at 28 days and 6 months after second vaccination
and 1 to 1,5 years after the intitial vaccination series.
- adverse events and
- levels of SARS-CoV-2 specific T and B cell responses and their durability 1
to 1,5 years after the intitial vaccination series
Other parameters:
- the association between baseline (immune) parameters and the immune response
to SARS-CoV-2 vaccination
- the neutralizing capacity of anti-COVID-19 antibodies against ancestral
SARS-CoV-2 and novel variants
- the incidence of SARS-CoV-2 infection and outcome of COVID-19 disease during
12 months after SARS-CoV-2 vaccination.
Part 2
The secondary endpoints of the second part of the study include
- mucosal antibody response at 28 days, 6 months after the 1st booster
vaccination (=3rd vaccination)
- adverse events and
- levels of SARS-CoV-2 specific T and B cell responses (subset of participants)
Background summary
An outbreak of a new corona virus started in China in December 2019. The virus
can cause COVID-19 disease. Most people who are infected with this virus have a
fever and respiratory complaints. In the Netherlands, but also worldwide,
measures are being taken to prevent further spread of the virus. In the
Netherlands, this coronavirus has now been detected in more than 690,000
people. A vaccine has recently been introduced on the market against this new
corona virus. The vaccine will first be given to vulnerable people who are
known to be at higher risk for a more serious course of COVID-19 disease. .
People with Down syndrome belong to this vulnerable group, they more often
suffer from respiratory infections, chronic inflammation and accelerated aging
due to a less well-functioning immune system. This study was set up by a team
of medical specialists and other experts. The research is coordinated from the
University Medical Center Utrecht (UMCU). The risk of severe course of
SARS-CoV-2 infection in people with Down Syndrome is substantially increased.
The risk of death is 3-10 fold higher than in healthy people. COVID vaccines
have been registered but none of them have been studied in people with Down
Syndrome. Vaccine responses in people with Down Syndrome is suboptimal.
Part 2
The results of part 1 of the study showed that antibody responses in adults
with down syndrome are lower than in the normal/healthy population. Based on
this an extra SARS-CoV-2 vaccination is recommended for all adults with Down
syndrome by the Health Council. The ministry of Health is currrently
considering whether to implement this. The PRIDE studyteam will vaccinate all
participants of the adult Down syndrome cohort. If they have already received
the third vaccination by the Dutch government or care takers, only the blood
withdrawals will remain.
For the children that participate in the PRIDE study, no results are known yet
and inclusion of participants is still ongoing. We would like to investigate
the immune response following booster vaccination in these children similar to
the adult population if they would be eligible for a booster or third
vaccination. The Health Council of the Netherlands recommended to not
routineously offer a booster vaccination to all children of 12-17 years.
Subsequently the Dutch government decided to make a booster vaccination
available for all children >12 years who (together with their parents) decide
to have a booster vaccination. We expect that a significant part of (the
parents of) the participating children will get a boostervaccination.
Study objective
To assess the antibody response after SARS-CoV-2 vaccination in people >=16
years and children with Down Syndrome.
Part 2
To assess the antibody response after a third SARS-CoV-2 vaccination in adults
and children with Down Syndrome and to compare this wiith healthy controls.
Durability time point
To asses the durability of the humoral and cellular immune response 1 to 1,5
years after the initial COVID vaccination series (vaccination 1 and 2) and at
least before the 3rd booster vaccination, in adults and children with Down
syndrome compared to controls.
In addition, the neutralizing capacity of SARS-CoV-2 antibodies against
ancestral SARS-CoV-2 and novel variants will be compared between cohorts at
this time point.
Study design
Prospective, observational parallel cohort study. People >=16 years with Down
Syndrome will be compared to healthy controls (household contacts).
In the pediatric part of the study children with Down Syndrome will be compared
to healthy children.
Part 2 of the PRIDE study is a non-randomised interventional study. All Adults
participating in the PRIDE study will be offered a third mRNA vaccination by
the PRIDE studyteam. Antibody titers will be measured at moment of the third
vaccination (<2 weeks before) and 4 weeks (3-6 weeks) after the third
vaccination. Adult participants or children who receive a 3rd mRNA vaccination
as part of the national COVID-19 immunisation program, will also be eligible
to participate in the study. From these participants only samples will be
collected.
The durability visit will be 1 to 1,5 years (with a minimal of 1 year) after
the initial COVID vaccination series (vaccination 1 and 2) and at least before
the 3rd booster vaccination.
For children from 6 months-4 years old, the primary vaccination series will
consist of 3 vaccins. The timing of study visits will be adjusted to this
resulting in the following scheme; baseline (T=1) before any vaccination, 4
weeks (range 3-6 weeks) after the 2nd vaccination (T=2), 3 weeks (range of 3-6
weeks) after the 3rd vaccination (T=3) and 6 months after the primary series
(T=4). In case of an natural COVID-19 infection, the vaccination scheme may be
adjusted. The study visits then will be adjusted to be in line with the
vaccinations.
Study burden and risks
There is no study-related risk. The burden is minimal. There will be blood
draws (4-5x), which is the most stressful part. Nasal mucosal lining fluid will
be collected at 2 timepoints (4 timepoints in part 2 in children). This can
give a short tickling sensation, but is not painful.
In addition the participants are asked to fill out the following questionnaires:
- COVID-19 questionnaire at baseline and 12 months after 2nd vaccination
- SAE diary during 7 days after each vaccination.
Individual participants will receive the results of the antibody titers after
the second COVID-19 vaccination (exact timepoint during the study is not yet
known), with an indication whether this is considered a protective titer or
not. If the participant does not have a protective antibody titer against
SARS-CoV-2 after the second vaccination, an additional booster vaccination will
be offered either as part of a study amendment or on an individual level if the
study results do not warrant an extra booster vaccination in this study
population.
It is also important to study vaccine effectiveness of COVID-19 vaccination in
children with Down syndrome. The working of the immune system (including
reaction to vaccination) is age-dependent and therefore studies about vaccine
effectivity in adults cannot be extrapolated to children. It is also important
to study vaccine effectiveness of COVID-19 vaccination in children with Down
syndrome. The working of the immune system (including reaction to vaccination)
is age-dependent and therefore studies about vaccine effectivity in adults
cannot be extrapolated to children.
Part 2
There are no study related risks, with a minimal burden. The additional burden
is minimal and consists of 1 vaccination, 2 extra blood draws and 1 extra
collection of nasal mucosal lining fluid. In addition they will fill out 1
extra COVID-19 questionnaire and 1 extra SAE diary. Studies reporting side
effects en reactogenicity of a third dose of the SARS-CoV-2 vaccin show limited
side effects, as seen in the initial vaccination regimen.
The individual participants will receive their personal results of the antibody
titer after the third SARS-CoV-2 vaccination (exact timepoint during the study
is not yet known).
POB 85090, Kamer E4.133.1 Heidelberglaan 100
Utrecht 3508 AB
NL
POB 85090, Kamer E4.133.1 Heidelberglaan 100
Utrecht 3508 AB
NL
Listed location countries
Age
Inclusion criteria
1. All patients have opted to receive routine COVID-19 vaccination.
2. Age: >=16 years or <16 years if vaccine is recommended for routine use for
that age group
3. Either Down syndrome or healthy household contact
Part 2
- All participants who participated in part 1 of the study and who have opted
to receive a third SARS-CoV-2 vaccination by the studyteam or the Dutch
government.
Additional Durability time point: All individuals already participating in the
PRIDE study are eligble to participate in this additional time point
Exclusion criteria
Down syndrome cohort: History of severe adverse reaction associated with a
vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of
the study intervention(s), organ transplant recipients, active malignancy or
completion of treatment for malignancy in previous 3 months, infection with
Human Immunodeficiency Virus (HIV), bleeding diathesis or condition associated
with prolonged bleeding that would, in the opinion of the investigator,
contraindicate intramuscular injection.
Healthy control cohort: as in Down Syndrome cohort plus active care for
inherited or acquired immune deficiency, any moderate to severe comorbidity for
which regular medical care is needed (pe heart failure, COPD, diabetes).
Part 2
Anaphylactic reaction to previous COVID-19 vaccination
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 | EUCTR2021-002613-34-NL |
| CCMO | NL76336.041.21 |