Primary objective - to describe immunogenicity and safety in healthy volunteers of the intradermal dermal delivery of a single fractional dose of 20µg mRNA-1273 LNP vaccine (Spikevax, Moderna) more than 3 months after primary vaccination with…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Immunogenicity:
- SARS-CoV-2-spike protein-specific binding IgG antibody levels
Safety:
- Local reactions (pain at the injection site, redness, and swelling)
- Reaction regional lymph nodes (pain, swelling)
- Use of antipyretics and painkillers
- Systemic events (fever, fatigue, headache, chills, vomiting, diarrhea, new or
worsened muscle pain, and new or worsened joint pain)
- AEs
- SAEs
Secondary outcome
- SARS-CoV-2-spike protein-specific binding IgG and IgA antibody levels and
RBD- specific binding IgG antibody levels in serum
- SARS-CoV 2 WT neutralizing antibody levels
Exploratory
- Number of Spike-protein specific proliferating B-cells, plasma cells and
B-memory cells
- INF-gamma concentration and other cytokine responses after over-night
incubation
Background summary
Currently, five vaccines are listed by the World Health Organization (WHO) for
emergency use. These vaccines are limited in supply, especially in low- and
middle-income countries, leading to substantial morbidity and mortality. A
large unvaccinated population continues to pose a threat of a continuous
emergence of new SARS-CoV-2 variants that may be more infectious, more
malignant and more resistant to vaccines than current strains. Despite the
COVID-19 Vaccines Global Access (COVAX) Facility initiated by the WHO to
provide vaccine access for low-income countries, probably 80% of the vaccine
needs of participating countries will not be met soon.
In addition, there is an increasing demand for revaccination of the
(vulnerable) population globally, because of waning immunity which will further
limit vaccine supplies. Exploring dose-sparing techniques, and future
self-application of vaccine, could therefore provide the solution to immunise
more people with the same vaccine stockpile.
The intramuscular injection (IM) is the standard inoculation route of vaccines.
However, the skin (dermis) is much richer in antigen presenting dendritic cells
than muscle [1]. In addition, the dermis contains an extensive lymphatic
network, which aids efficient transport of vaccine antigen and antigen
presenting Langerhans and dendritic cells to the regional lymph nodes [2]. As a
consequence, a fractional vaccine dose introduced directly into the dermis
(intradermal administration, ID) might be as effective as the intramuscular
administration of the full standard dose to achieve a protective immune
response. This principle has recently been demonstrated for the ID dermal
delivery of one-fifth fractional dose mRNA-1273 (Spikevax, Moderna) vaccine
[3].
However, needle-based immunisation has several limitations. Fear of needles
makes immunisation a stressful event. In addition, needle stick injuries, as
well as unsafe injection practices carry serious health risks. Therefore, the
development of needle-free delivery has been identified as an important goal in
global health care [4]. The WHO reported that microneedle vaccine delivery is
top priority and requires additional research to explore the benefits in more
detail. A big advantage of intradermal delivery via a microneedle array/patch
is not only the absence of needles and pain since no nerves are at the
proximity where the needles are presented, but also the local delivery close to
immune cells as with the above mentioned intradermal injection enables a much
lower dose as compared to IM dosing. And since with the patch a larger skin
surface is involved as compared to intradermal injection, even lower doses are
possibly still immunogenic.
Study objective
Primary objective
- to describe immunogenicity and safety in healthy volunteers of the
intradermal dermal delivery of a single fractional dose of 20µg mRNA-1273 LNP
vaccine (Spikevax, Moderna) more than 3 months after primary vaccination with
Comirnaty (Pfizer) vaccine.
Secondary objectives
- to describe the kinetics of the SARS-CoV-2 anti-Spike1 (S1) and Region
Binding Domain (RBD) IgG and IgA binding antibodies elicited by intradermal or
intramuscular delivery of mRNA-1273 vaccine in healthy volunteers after a
single fractional dose of 20µg mRNA-1273 LNP vaccine
- to describe the kinetics of the SARS-CoV-2 neutralising antibodies elicited
by intradermal or intramuscular delivery of mRNA-1273 vaccine in healthy
volunteers after a single fractional dose of 20µg mRNA-1273 LNP vaccine
Exploratory objectives:
- to describe the kinetics of memory B-cell and plasma cell responses elicited
by intradermal or intramuscular delivery of mRNA-1273 vaccine of a single
fractional dose of 20µg mRNA-1273 LNP vaccine (Spikevax, Moderna)
- to describe the interferon-gamma release in whole blood in response to
SARS-CoV 2 peptides after intradermal or intramuscular delivery of mRNA-1273
vaccine of a single fractional doses of 20µg mRNA-1273 LNP vaccine (Spikevax,
Moderna)
Study design
This is a Phase 2a, open-label, randomised-controlled, proof-of-concept vaccine
study
Intervention
Intervention group (n=10): Participants will receive 20 µg of mRNA-1273 vaccine
through the intradermal route using a micro-needle delivery system.
Control group (n=10): Participants will receive 20 µg of mRNA-1273 vaccine
through the intramuscular route
Study burden and risks
Burden of receipt of the vaccine by intradermal (ID) administration (adverse
events):
The mRNA-1273 vaccine (Spikevax, Moderna) has been approved for mass
vaccination by the EMA in Europe and by the Medicine Evaluation Board in the
Netherlands. The most frequent side effects of intramuscular administration of
100 µg mRNA-1273 vaccine were injection site pain (92%); fatigue (70%);
headache (64%); myalgia (61%); arthralgia (46%); chills (45%); nausea and
vomiting (23%); swelling axillar lymph nodes 20%); pyrexia (15%) and injection
site swelling and redness (15%) usually mild or moderate in intensity and
resolving within a few days after vaccination. Side effects were reported more
frequently after the second dose. The frequency of anaphylactic reactions after
the mRNA vaccine by Moderna is estimated to be around 2.5:1000,000 [5]. Three
cases of Bell*s palsy have been reported in the vaccine group and one in the
placebo group. In 19 young adults, pericarditis/myocarditis has been reported
in a population of over 20 million doses.
In a recent study we showed that the ID administration of 10 µg and 20 µg
mRNA-1273 vaccine with needle and syringe resulted in a robust, homogeneous,
immune response with an acceptable safety profile in healthy adults aged 18-30
years [IDSCOVA]. The most commonly reported adverse reactions were
short-lasting and consisted of mild pain, itching, erythema and swelling at the
injection site. These local reactions are similar to those reported after
intradermal vaccination with other vaccines.
Burden of postponing their regular booster (i.e. revaccination) in the national
vaccination programme:
Participants are willing to postpone their regular COVID revaccination upon
invitation by the municipal health center or general practitioner until the day
after the final study sampling (D29), which is approximately four weeks after
receiving the intervention. Participants who have postponed their regular
COVID-19 revaccination through the national immunisation program to participate
in this study will be offered their regular vaccination after D29 of the study.
Burden of participation in the study (time and blood volume):
Participation in the study requires four site visits. Screening (D0) will take
60 minutes, vaccination (D1) will take 90 minutes since the vaccine-patch
formulation will have to be prepared on the day of the vaccination. Blood
sampling on D29 will take 15 minutes. In total this is 165 minutes without
travelling to and from the LUMC. During the visits blood will be collected for
antibody testing (maximal total blood volume 100 mL in the study).
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
- Male or female participants between the ages of 18 and 50 years, inclusive at
randomisation.
- Previously vaccinated with Comirnaty (Pfizer) or Spikevax (Moderna) at least
3 months before inclusion.
- Healthy participants who are determined by medical history and clinical
judgment of the investigator to be eligible for inclusion in the study. Healthy
participants with preexisting stable disease, defined as disease not requiring
significant change in therapy or hospitalisation for worsening disease during
the 6 weeks before enrolment, can be included.
- Participants who are willing and able to comply with all scheduled visits,
vaccination plan, laboratory tests, lifestyle considerations, and other study
procedures.
- Participants are willing to postpone their regular COVID-19 revaccination
upon invitation by the municipal health center or general practitioner until
four weeks after receiving the intervention (after the last sampling of
D29+/-1).
- Capable of giving personal signed informed consent, which includes compliance
with the requirements and restrictions listed in the ICD and in this protocol.
Exclusion criteria
- Other medical or psychiatric condition including recent (within the past
year) or active suicidal ideation/behaviour or laboratory abnormality that may
increase the risk of study participation or, in the investigator*s judgment,
make the participant inappropriate for the study.
- History of severe adverse reaction associated with a vaccine and/or severe
allergic reaction (e.g., anaphylaxis) to any component of the study
intervention(s).
- Receipt of medications intended to prevent COVID-19.
- Previous microbiological diagnosis of COVID-19 less than 3 months ago.
- Previous COVID-19 (re)vaccination other than Comirnaty (Pfizer) or Spikevax
(Moderna) less than 3 months ago
- Individuals at high risk for severe COVID-19 (e.g. BMI > 40, diabetes, heart-
end/or lung disease), who are planned to receive COVID vaccine within the next
two months.
- Immunosuppressed individuals with known or suspected immunodeficiency, as
determined by history.
- Individuals with an active autoimmune disease requiring therapeutic
intervention.
- Receipt of systemic or topical corticosteroids.
- Bleeding diathesis or condition associated with prolonged bleeding that
would, in the opinion of the investigator, contraindicate intramuscular
injection.
- Women who are pregnant or breastfeeding.
- Planned pregnancy within four weeks after injection.
- Positive serological test for SARS-CoV-2 anti-N IgM and/or IgG antibodies at
screening visit.
- SARS-CoV-2 PCR-positive mid-turbinate/throat swab at the screening before
receipt of the vaccine dose.
- Participation in other studies involving study intervention within 28 days
prior to study entry and/or during study participation.
- Receipt of any other non-study vaccine within 28 days, before receipt of the
study dose.
- Anticipated receipt of any other non-study vaccine within 28 days, after the
study dose administration.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-006754-31-NL |
| CCMO | NL80101.058.22 |