NCT05315362: MILESTONE

Establishing Immunogenicity and Safety of Needle-free Intradermal Delivery of mRNA COVID-19 Vaccine

Status unknown Phase 2 Last updated 22 April 2022

What this trial tests

Phase 2 trial testing solid microneedle skin patch in Vaccination; Infection in 20 participants. Status unknown.

Timeline

1 May 2022

Primary endpoint
1 September 2022

1 May 2023

Quick facts

Lead sponsor	Leiden University Medical Center
Phase	Phase 2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	20
Start date	1 May 2022
Primary completion	1 September 2022
Estimated completion	1 May 2023
Sites	1 location across Netherlands

Drugs / interventions tested

• solid microneedle skin patch
• mRNA-1273 — full drug profile →
• standard needle

Conditions studied

• Vaccination; Infection — all drugs for Vaccination; Infection →
• COVID-19 — all drugs for COVID-19 →

Sponsor

Leiden University Medical Center

Who can join

Adults 18 to 40, any sex, with Vaccination; Infection or COVID-19. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Nanoparticle technology for mRNA: Delivery strategy, clinical application and developmental landscape.
   Li X, Qi J, Wang J, Hu W, et al · · 2024 · cited 47× · PMID 38169577 · DOI 10.7150/thno.84291
2. Navigating the intricate in-vivo journey of lipid nanoparticles tailored for the targeted delivery of RNA therapeutics: a quality-by-design approach.
   Haghighi E, Abolmaali SS, Dehshahri A, Mousavi Shaegh SA, et al · · 2024 · cited 28× · PMID 39543630 · DOI 10.1186/s12951-024-02972-w
3. Engineering microneedles for biosensing and drug delivery.
   Zhao P, Zhou Z, Wolter T, Womelsdorf J, et al · · 2025 · cited 19× · PMID 40519362 · DOI 10.1016/j.bioactmat.2025.05.027
4. Beyond the Needle: Innovative Microneedle-Based Transdermal Vaccination.
   Nguyen HX. · · 2025 · cited 15× · PMID 39982324 · DOI 10.3390/medicines12010004
5. 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.
   Prins MLM, Prins C, de Vries JJC, Visser LG, et al · · 2023 · cited 12× · PMID 37473964 · DOI 10.1016/j.virusres.2023.199175
6. From mechanism to applications: Advanced microneedles for clinical medicine.
   Yang Y, Sun H, Sun X, Wang Y, et al · · 2025 · cited 9× · PMID 40463395 · DOI 10.1016/j.bioactmat.2025.04.025
7. Advances in locally administered nucleic acid therapeutics.
   Shen J, Duan X, Xie T, Zhang X, et al · · 2025 · cited 5× · PMID 40144794 · DOI 10.1016/j.bioactmat.2025.02.043
8. Microneedle Technology for Overcoming Biological Barriers: Advancing Biomacromolecular Delivery and Therapeutic Applications in Major Diseases.
   Ye W, Wu W, Peng S, Jiang Z, et al · · 2025 · cited 2× · PMID 41244514 · DOI 10.34133/research.0879