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

Primary Purpose

Vaccination; Infection, COVID-19

Status

Recruiting

Phase

Phase 2

Locations

Netherlands

Study Type

Interventional

Intervention

solid microneedle skin patch

mRNA-1273

standard needle

About this trial

This is an interventional prevention trial for Vaccination; Infection

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Previously vaccinated with Comirnaty (Pfizer) and/or previously contracted COVID-19 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).
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.

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.
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.
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.

Sites / Locations

Leiden University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Intervention group - intradermal vaccination with patch

Control group - intramuscular vaccination with standard needle

Arm Description

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

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

Outcomes

Primary Outcome Measures

SARS-CoV-2-spike protein-specific binding IgG antibody levels

adverse events

local and systemic reactions after intradermal vaccination with a solid microneedle patch

Secondary Outcome Measures

SARS CoV 2 neutralizing antibody levels

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

Full Information

NCT ID

NCT05315362

First Posted

April 6, 2022

Last Updated

April 14, 2022

Sponsor

Leiden University Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT05315362

Brief Title

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

Acronym

MILESTONE

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Recruiting

Study Start Date

May 1, 2022 (Anticipated)

Primary Completion Date

September 1, 2022 (Anticipated)

Study Completion Date

May 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Leiden University Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

Detailed 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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Vaccination; Infection, COVID-19

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

open-label, randomised-controlled, proof-of-concept vaccine study

Masking

None (Open Label)

Masking Description

only laboratory personnel is masked. Because of the different administration routes it is not possible to mask the participants or investigators

Allocation

Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Intervention group - intradermal vaccination with patch

Arm Type

Experimental

Arm Description

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

Arm Title

Control group - intramuscular vaccination with standard needle

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Device

Intervention Name(s)

solid microneedle skin patch

Intervention Description

intradermal vaccination with a skin patch

Intervention Type

Biological

Intervention Name(s)

mRNA-1273

Intervention Description

administration of mRNA-1273 vaccine

Intervention Type

Device

Intervention Name(s)

standard needle

Intervention Description

intramuscular vaccination with a standard needle

Primary Outcome Measure Information:

Title

SARS-CoV-2-spike protein-specific binding IgG antibody levels

Description

SARS-CoV-2-spike protein-specific binding IgG antibody levels

Time Frame

3 months

Title

adverse events

Description

local and systemic reactions after intradermal vaccination with a solid microneedle patch

Time Frame

1 month

Secondary Outcome Measure Information:

Title

SARS CoV 2 neutralizing antibody levels

Description

SARS CoV 2 neutralizing antibody levels

Time Frame

3 months

Title

Number of Spike-protein specific proliferating B-cells, plasma cells and B-memory cells

Description

Number of Spike-protein specific proliferating B-cells, plasma cells and B-memory cells

Time Frame

6 months

Title

INF-gamma concentration and other cytokine responses after over-night incubation

Description

INF-gamma concentration and other cytokine responses after over-night incubation

Time Frame

3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Previously vaccinated with Comirnaty (Pfizer) and/or previously contracted COVID-19 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). 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. 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. 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. 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Anna H Roukens, MD PhD

Phone

+31715262613

a.h.e.roukens@lumc.nl

First Name & Middle Initial & Last Name or Official Title & Degree

Leo G Visser, MD PhD

Phone

+31715262613

l.g.visser@lumc.nl

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anna H Roukens, MD PhD

Organizational Affiliation

Leiden University Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Leiden University Medical Center

City

Leiden

ZIP/Postal Code

2333ZA

Country

Netherlands

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Anna H Roukens, MD, PhD

Phone

+31715262613

a.h.e.roukens@lumc.nl

First Name & Middle Initial & Last Name & Degree

Leo G Visser, MD, PhD

Phone

+31715262613

l.g.visser@lumc.nl

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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