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ID
Source
Brief title
Health condition
COVID-19
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Nature, frequency and severity of local reactions. Solicited adverse events include: pain, redness and swelling at the injection site and pain and swelling at the regional lymph nodes
- Nature, frequency and severity of systemic events. Solicited adverse events include: fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain.
- Use of antipyretics and painkillers
- SARS-CoV-2 WT neutralizing antibody titers rate on Day 43
- SARS-CoV-2-spike protein–specific binding IgG level on D 43
Secondary outcome
- Kinetics of SARS-CoV 2 WT neutralizing antibody (seroconversion, GMT and GM fold rise) and of SARS-CoV-2-spike protein-specific binding IgG antibody levels and RBD- specific binding IgG antibody levels (seroconversion, GMC and GM fold rise) over time
- Positive SARS-CoV-2 PCR (with or without clinical symptoms) of nasopharyngeal/throat swab
- Seroconversion SARS-CoV-2 (Nucleocapsid Serology)
- Proportion of afucosylated IgG variants
- SARS-CoV-2 WT neutralizing antibodies in nasal fluid
- SARS-CoV-2-spike protein–specific binding IgG and IGA antibody levels and RBD- specific binding IgG and IGA antibody levels in nasal fluid
- Parameters quantifying germinal center activity
- Whole blood interferon-gamma release assay to SARS-CoV-2 antigen
Background summary
SUMMARY
Rationale: The intradermal route is a highly effective way to administer vaccines. As a consequence, a fractional vaccine dose introduced directly into the papillary dermis (intradermal administration, ID) might be as effective as the intramuscular administration of the full standard dose to achieve a protective immune response. Especially in circumstances of limited vaccine stockpiles, vaccination with a fractional dose through the intradermal route can be applied as a dose-sparing strategy. Because the vaccine is administered much more superficially, the local side effects, such as redness and induration, are more visible at the site of injection than after intramuscular injection.
Globally the race to national mass vaccination campaigns to protect against infection with SARS-CoV-2 has started. Production limitations threaten to delay the roll-out of the national vaccination campaigns. In preclinical studies the intradermal route has been shown to be a very effective way for mRNA vaccine administration. If the intradermal route would be a safe and effective route for a fractional dose of the mRNA COVID vaccine, many more people could be vaccinated with the same limited amount of vaccine.
vaccine.
Objectives:
Primary objectives:
- to describe tolerability, safety and immunogenicity in healthy adults of the intradermal delivery of one or two fractional doses of 10 μg and 20 μg mRNA-1273 LPN vaccine (Moderna).
- to compare the immunogenicity in healthy adults of the intradermal delivery of two fractional dose of 20 μg mRNA-1273 LPN with that of two doses of 20 μg mRNA-1273 vaccine through intramuscular delivery on Day 43.
- to determine non-inferiority of the virus neutralizing antibody response elicited by intradermal delivery of mRNA-1273 vaccine in healthy adults after two fractional doses of 20 μg with the responses to two doses of 100 μg mRNA-1273 vaccine through intramuscular delivery on Day 43. On group receives the fractional dose (20ug) intradermally via 'Mantoux technique' and one group with Bella-mu needle for intradermal administration.
Secondary objectives:
- to describe the kinetics of the humoral immune responses elicited by intradermal or intramuscular delivery of mRNA-1273 vaccine in healthy adults after 1 and 2 fractional doses of 20 μg, and standard intramuscular delivery of 100 μg.
- to document symptomatic and asymptomatic infection with SARS-CoV-2
Exploratory objectives:
- to describe the nasal mucosal immune response elicited by intradermal or intramuscular delivery of mRNA-1273 vaccine in healthy adults after 1 or 2 fractional doses of 20 μg, and standard intramuscular delivery of 100 μg
- to describe the glycosylation of SARS-CoV-2 antibodies elicited by intradermal or intramuscular delivery of mRNA-1273 vaccine in healthy adults after 1 or 2 fractional doses of 20 μg, and standard intramuscular delivery of 100 μg.
- to describe the T follicular helper cell kinetics elicited by intradermal or intramuscular delivery of mRNA-1273 vaccine in healthy adults after 1 or 2 fractional doses of 20 μg, and standard intramuscular delivery of 100 μg.
- to describe the memory B-cell and plasma cell response elicited by intradermal delivery of mRNA-1273 vaccine in healthy adults after 1 or 2 fractional doses of 20 μg, and standard intramuscular delivery of 100 μg.
Study design: This is a Phase 1/Phase 2a, open-label, randomized-controlled, dose-escalation, proof-of-concept vaccine study.
Study population: Health adults aged 18 - 30 years
Intervention group: Participants will receive 10 μg or 20 μg mRNA-1273 vaccine followed by a second dose on day 28 through the intradermal route.
Comparison group: Participants will receive 20 μg or 100 μg mRNA-1273 vaccine followed by a second dose on day 28 through the intramuscular route.
Main study parameters/endpoints:
- Local reactions and systemic events self-reported by e-diary on a daily basis over a 2-week period, as well as by structured interviews by telephone/video call on D2, D3, D4, D8, D15, D29, D30, D31, D32, D36, and D43
- Adverse events (AEs) from Dose 1 to one month after the last dose
- Serious AEs (SAEs) from Dose to six months after the last dose
- Seroconversion for anti-spike IgG antibodies (D0, D29, D36, D43, M7, M13)
- Geometric mean titers (GMT) for anti-spike IgG antibodies (D0, D29, D36, D43, M7, M13)
- Seroconversion for neutralizing antibodies to SARS-CoV2 (D0, D29, D36, D43, M7, M13)
- GMT for neutralizing antibodies to SARS-CoV2 (D0, D29, D36, D43, M7, M13)
Study objective
The intradermal vaccination of a fractional dose of mRNA-1273 LPN vaccine (Moderna) is safe and non-inferior in eliciting neutralizing antibodies against SARS-CoV-2 to the standard dose injected intramuscularly
Study design
D0, D2, D3, D4, D8, D15, D29, D30, D31, D32, D36, D43, M7, M13 (safety and immunogenicity, D = day, M = month)
Intervention
intradermal injection of a fractional dose (10 μg and 20 μg) mRNA-1273 LPN vaccine compared to intramuscular injection of the standard dose (100 μg) mRNA-1273 LPN vaccine
Inclusion criteria
- Male or female participants between the ages of 18 and 30 years, inclusive at randomization.
- 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 hospitalization 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.
- 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 sterilized 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.
- Receipt of any other non-study vaccine within 28 days, before first study dose.
- Anticipated receipt of any other non-study vaccine within 28 days, after last study dose administration
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL9275 |
| CCMO | NL76702.058.21 |
| OMON | NL-OMON51021 |