Establishing the safety, tolerability and immunogenicity of intradermal delivery of mRNA SARS-CoV-2 vaccine in healthy adults

Phase 2

Completed

Conditions: COVID-19
10047438

Registration Number: NL-OMON51021

Lead Sponsor: eids Universitair Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 245

Inclusion Criteria

- Male or female participants between the ages of 18 and 30 years, inclusive at
randomisation.
- Stage 4 additional group: healthy male and female participants between the
ages of 18 and 40 years, and having received the primary mRNA COVID-19 vaccine
series approximately 6 months earlier
- 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 enrollment, can be included.
- 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.
- Females only: female volunteers of childbearing potential (i.e. have a uterus
and are neither surgically sterilised nor postmenopausal) must not be pregnant
or breastfeeding. They should agree to use adequate contraception at least up
to four weeks following the final dose of mRNA-1273 vaccine.

Exclusion Criteria

- Other medical or psychiatric condition including recent (within the past
year) or active suicidal ideation/behavior 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 (eg, anaphylaxis) to any component of the study
intervention(s).
- Receipt of medications intended to prevent COVID-19.
- Previous clinical or microbiological diagnosis of COVID-19.
- Individuals at high risk for severe COVID-19, 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 a history of autoimmune disease or 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 the final injection.
- Positive serological test for SARS-CoV-2 IgM and/or IgG antibodies at the
screening visit.
- SARS-CoV-2 PCR-positive nasopharyngeal/throat swab at the screening before
receipt of first vaccine dose.
- Participation in other studies involving study intervention within 28 days
prior to study entry and/or during study participation.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>- Nature, frequency and severity of local reactions. Solicited adverse events<br /><br>include: pain, redness and swelling at the injection site and pain and swelling<br /><br>at the regional lymph nodes<br /><br>- Nature, frequency and severity of systemic events. Solicited adverse events<br /><br>include: fever, fatigue, headache, chills, vomiting, diarrhoea, new or worsened<br /><br>muscle pain, and new or worsened joint pain.<br /><br>- Use of antipyretics and painkillers<br /><br>- SARS-CoV 2 WT neutralising antibody titres rate on Day 43<br /><br>- SARS-CoV-2-spike protein-specific binding IgG level on D43<br /><br>- To determine non-inferiority of the humoral immune responses elicited by<br /><br>intradermal by means of the U-needle or intramuscular delivery of mRNA-1273<br /><br>vaccine in healthy adults after two fractional doses of 20 µg, and standard<br /><br>intramuscular delivery of 100 µg<br /><br>- for the booster, the above will be measured on Day 29 after the booster</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Kinetics of SARS-CoV 2 WT neutralising antibody (seroconversion, GMT and GM<br /><br>fold rise) and of SARS-CoV-2-spike protein-specific binding IgG antibody levels<br /><br>and RBD- specific binding IgG antibody levels (seroconversion, GMC and GM fold<br /><br>rise) over time<br /><br>- Positive SARS-CoV-2 PCR (with or without clinical symptoms) of<br /><br>nasopharyngeal/throat swab<br /><br>- Seroconversion SARS-CoV-2 (Nucleocapsid Serology)<br /><br>- Proportion of afucosylated IgG variants<br /><br>- SARS-CoV-2 WT neutralising antibodies in nasal fluid<br /><br>- SARS-CoV-2-spike protein-specific binding IgG and IGA antibody levels and<br /><br>RBD- specific binding IgG and IGA antibody levels in nasal fluid<br /><br>- Parameters quantifying germinal centre activity<br /><br>- Whole blood interferon-gamma release assay to SARS-CoV-2 antigen<br /><br>- To compare the diameter of the wheal after intradermal injection by standard<br /><br>or U-needle</p><br>