Establishing Immunogenicity and Safety of Needle-free Intradermal Delivery of mRNA COVID-19 Vaccine
MILESTONE
1 other identifier
interventional
20
1 country
1
Brief Summary
COVID-19 vaccines are limited in supply, especially in low- and middle-income countries, leading to substantial morbidity and mortality. 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 population globally, because of waning immunity which will further limit vaccine supplies. Exploring dose-sparing techniques, 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. 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. 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. 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 solid needle 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. In this study, we will investigate the immunogenicity and safety in healthy volunteers of the needle-free intradermal 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 and/or after having contracted COVID-19.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started May 2022
Shorter than P25 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 6, 2022
CompletedFirst Posted
Study publicly available on registry
April 7, 2022
CompletedStudy Start
First participant enrolled
May 1, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2023
CompletedApril 22, 2022
April 1, 2022
4 months
April 6, 2022
April 14, 2022
Conditions
Outcome Measures
Primary Outcomes (2)
SARS-CoV-2-spike protein-specific binding IgG antibody levels
SARS-CoV-2-spike protein-specific binding IgG antibody levels
3 months
adverse events
local and systemic reactions after intradermal vaccination with a solid microneedle patch
1 month
Secondary Outcomes (3)
SARS CoV 2 neutralizing antibody levels
3 months
Number of Spike-protein specific proliferating B-cells, plasma cells and B-memory cells
6 months
INF-gamma concentration and other cytokine responses after over-night incubation
3 months
Study Arms (2)
Intervention group - intradermal vaccination with patch
EXPERIMENTALParticipants will receive 20 µg of mRNA-1273 vaccine through the intradermal route using a solid micro needle delivery system
Control group - intramuscular vaccination with standard needle
ACTIVE COMPARATORParticipants will receive 20 µg of mRNA-1273 vaccine through the intramuscular route
Interventions
intradermal vaccination with a skin patch
administration of mRNA-1273 vaccine
intramuscular vaccination with a standard needle
Eligibility Criteria
You may qualify if:
- 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).
- Capable of giving personal signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.
You may not qualify if:
- 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.
- Previous COVID-19 vaccination other than Comirnaty (Pfizer)
- 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.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Leiden University Medical Center
Leiden, 2333ZA, Netherlands
Related Publications (1)
Prins MLM, Prins C, de Vries JJC, Visser LG, Roukens AHE. Establishing immunogenicity and safety of needle-free intradermal delivery by nanoporous ceramic skin patch of mRNA SARS-CoV-2 vaccine as a revaccination strategy in healthy volunteers. Virus Res. 2023 Sep;334:199175. doi: 10.1016/j.virusres.2023.199175. Epub 2023 Jul 21.
PMID: 37473964DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Anna H Roukens, MD PhD
Leiden University Medical Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- only laboratory personnel is masked. Because of the different administration routes it is not possible to mask the participants or investigators
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
April 6, 2022
First Posted
April 7, 2022
Study Start
May 1, 2022
Primary Completion
September 1, 2022
Study Completion
May 1, 2023
Last Updated
April 22, 2022
Record last verified: 2022-04
Data Sharing
- IPD Sharing
- Will not share