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

COVID-19 Clinical Trial

Official title: Establishing Immunogenicity and Safety of Needle-free Intradermal Delivery by Solid Micro Needle Skin Patch of mRNA SARS-CoV-2 Vaccine as a Revaccination Strategy in Healthy Volunteers

Status Recruiting

Clinical Trial 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.

Clinical Trial Description

Objectives Primary objective

• to describe 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 have contracted COVID-19.

Secondary objectives

• to describe the kinetics of the SARS-CoV-2 anti-Spike1 (S1) and Region Binding Domain (RBD) IgG binding antibodies elicited by needle-free 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 needle-free 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 needle-free 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 needle-free 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

Study population:

Healthy volunteers aged 18 - 40 years who have been vaccinated with Comirnaty (Pfizer) vaccine at least 3 months before

Intervention group:

Participants will receive 20 µg of mRNA-1273 vaccine through the needle-free intradermal route using a micro-needle delivery system.

Control group:

Participants will receive 20 µg of mRNA-1273 vaccine through the intramuscular route

Main study parameters/endpoints:

• Solicited local reactions and systemic events self-reported by diary on a daily basis over a 2-week period, telephone interview on D4, as well as by on site visits on D15 and D29

• Adverse events (AEs) until two weeks after administration

• Serious AEs (SAEs) until six months after administration

• Seroconversion for anti-spike IgG antibodies (D29)

• Geometric mean concentrations (GMC) for anti-spike IgG antibodies (D1, D29) ;

Related Conditions & MeSH terms

• COVID-19
• Vaccination; Infection

• NCT number: NCT05315362
• Study type: Interventional
• Source: Leiden University Medical Center
• Contact: Anna H Roukens, MD PhD
• Phone: +31715262613
• Email: a.h.e.roukens@lumc.nl
• Status: Recruiting
• Phase: Phase 2
• Start date: May 1, 2022
• Completion date: May 1, 2023