Randomized, controlled, multicenter Phase I/II study comparing the safety and immunogenicity of a booster dose of an intranasal COVID-19 vaccine expressing SARS-CoV-2 N/S recombinant proteins with a booster dose of COVID-19 mRNA vaccine in healthy adults

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Inserm, Centre Hospitalier Regional Universitaire De Tours

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

9 May 2025 → ongoing

Decision date (initial)

2025-01-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Direction générale de l'offre des soins (DGOS)

External identifiers

EU CT number

2024-510589-17-00

ClinicalTrials.gov

NCT06821126

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Phase I
To evaluate the safety of three different doses (20 µg, 60 µg and 120 µg) of a booster of an intranasal COVID-19 vaccine (LVT-001) expressing SARS-CoV-2 N/S recombinant protein in healthy volunteers.

Phase II
To evaluate, from nose swabs, the superiority of a booster dose of an intranasal COVID-19 vaccine (LVT-001) expressing SARS-CoV-2 N/S recombinant protein versus a booster dose of intramuscular COVID-19 mRNA vaccine (Pfizer-BioNTech) in healthy adult volunteers in terms of mucosal humoral immune response at D28.

Secondary objectives 9

1. To evaluate, from nose swabs, the mucosal humoral immune response by measuring anti-S and anti-N IgA concentrations specific to the intranasal vaccine N/S recombinant proteins by ELISA at D0, D7 (Phase I), D14, D28 (Phase I), M3, M6 and M12 respectively in each arm.
2. To evaluate, from nose swabs, the mucosal neutralizing immune response specific to the intranasal vaccine N/S recombinant proteins by PRNT and VLP assays test at D0, D7 (Phase I), D14, D28, M3, M6 and M12 respectively in each arm.
3. To evaluate, from serum samples, the systemic humoral immune response by measuring anti-S and anti-N IgG concentrations specific to the intranasal vaccine N/S recombinant proteins by ELISA at D0, D7 (Phase I), D14, D28, M3, M6 and M12, respectively in each arm.
4. To evaluate, from serum samples, the systemic humoral neutralizing immune response specific to the intranasal vaccine N/S recombinant proteins by PRNT and VLP assays at D0, D7 (phase I), D14, D28, M3, M6 and M12, respectively, in each arm.
5. To evaluate, from blood samples, the systemic cellular immune response against N and S antigens by measuring the number of specific IFN-gamma-secreting T lymphocytes using the ELISpot techniques at D0, D7 (Phase I), D14, D28, M3, M6 and M12 in each arm (subset of trial participants recruited in Tours center only).
6. To evaluate the proportion of participants with confirmed COVID-19 infections in each arm between D0 and M12.
7. To identify the variants of the SARS-CoV-2 virus that escape vaccination.
8. To evaluate the proportion of participants with serious COVID-19 infections in each arm between D0 and M12.
9. For Phase II only: To evaluate the safety and tolerability of the LVT-001 vaccine.

Conditions and MedDRA coding

Healthy volunteers

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

National Agency For The Safety Of Medicine And Health Products

Plan to share IPD

Yes

IPD plan description

The trial data will not be publicly available because they are sensitive health data that could compromise the confidentiality of the participants. This is in accordance with French and European legislation on clinical trial and personal health data. Nevertheless, the trial dataset that underlie the results reported in the publication or any trial data set wishing to be reused for a new research project in the field of respiratory infectious diseases can be made available through a request to the Scientific Committee or to the cosponsors and the coordinating investigator if the Scientific Committee is not anymore active. In general, the final version of articles and scientific communications, and any written or oral communication relating to the trial, must be sent to the cosponsors for review, and must receive the prior approval of the coordinating investigator and the Scientific Committee.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Written informed consent obtained from the participant.
2. Agree to stay in the geographical area of one of the clinical sites for the duration of the trial.
3. Agree to implement barrier measures as much as possible (washing hands and wearing a mask) against COVID-19 and respiratory infections between D0 and D28.
4. Agree to be registered in the computerized file of the Ministry of Health (VRB).
5. Be affiliated to French social security system.
6. Be male or female between the ages of ≥ 18 and ≤ 55 years for phase I and ≥ 18 and ≤ 60 years for phase II.
7. Good general health as determined at the discretion of the investigator (vital signs, medical history, and physical examination).
8. BMI: 18,5 kg/m² ≤ BMI ˂30kg/m².
9. Received at least 3 doses of a COVID-19 mRNA vaccine, last booster dose received at least 6 months prior to trial vaccine administration OR 2 doses of a COVID-19 mRNA vaccine and confirmed SARS-CoV-2 infection at least 6 months prior to inclusion in the trial.
10. Has expressed interest and availability to meet the trial requirements.
11. For a woman of childbearing potential, plan to be non-pregnant AND use of highly effective contraception from screening until the end of the trial.
12. Agree to abstain from donating blood/plasma or any other bodily fluids from the time of vaccination until 1 year after vaccination (only for LVT-001 vaccine).

Exclusion criteria 27

1. Temperature ≥38.0°C or symptoms of acute self-limiting illness such as upper respiratory tract infection or gastroenteritis within three days prior to vaccine dose.
2. Any form of contraindication to the trial vaccines tested.
3. History of chronic rhinitis, nasal septal defect, cleft palate, nasal polyps, or other nasal abnormality that might alter nasal mucosa and affect vaccine response.
4. A piercing or obstruction in the nostrils that could impede vaccine administration.
5. Previous nasal surgery or nasal cauterization.
6. History of frequent epistaxis.
7. Virologically documented (PCR or antigenic test) history of COVID-19 in the past 6 months.
8. Positive COVID-19 PCR test at screening visit.
9. Medical problems due to alcohol.
10. Illicit drug use within the past 12 months.
11. Participation in another trial within 60 days prior to the enrolment visit or planned participation during the present trial period in another clinical study investigating a vaccine, drug, medical device, or medical procedure. Note: Participation in an observational study is allowed.
12. Received influenza vaccination within 14 days prior to trial vaccination, or any other licensed vaccine within 4 weeks prior to study vaccination.
13. Vaccination with a COVID-19 vaccine other than mRNA vaccine.
14. Known sensitivity to any of the ingredients of the trial vaccines.
15. Known allergic reaction to plastic.
16. Positive serology for hepatitis B (HBsAg), C (anti-HCV antibodies) and HIV 1-2.
17. History of severe adverse events following vaccine administration including anaphylactic reaction and associated symptoms such as rash, breathing problems, angioedema, and abdominal pain, or a history of allergic reaction that could be triggered by a component of the SARS-CoV-2 vaccine at the time of the first vaccine administration.
18. Pregnancy positive test (βHCG test) or pregnancy or breastfeeding.
19. Received immunoglobulin or other blood products within three months prior to inclusion or planned administration before the trial completion.
20. Received an immunosuppressive therapy for underlying disease or a treatment with immunosuppressive or cytotoxic drugs or a cancer chemotherapy or radiation therapy within the previous 36 months.
21. Received drugs such as corticosteroids at a dosage > 10 mg prednisone equivalent/day or inhalers corticosteroids, within 3 months prior to inclusion (excluding corticosteroid topical preparations for cutaneous application).
22. Abnormal and deemed clinically significant result by the investigator following the analyzes carried out at the time of the screening visit (any grade 4 biological result, even if deemed not clinically significant by the investigator, constitutes an exclusion criterion).
23. History of severe psychiatric disorders that may affect participation in the trial.
24. Any other serious chronic illness requiring immediate monitoring by a hospital specialist.
25. Any other condition that, in the opinion of the investigator, would compromise the safety or rights of a volunteer participating in the trial or render the subject unable to comply with the protocol.
26. Phase II only: Participants included in phase I will not be included in phase II.
27. Participants under legal protection (e.g., guardianship, tutorship).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Phase I: Proportion of participants experiencing an immediate AE within an hour and half following vaccine administration.
2. Phase I: Proportion of participants experiencing solicited local reactogenicity and systemic signs and symptoms for 7 days and 14 days respectively following vaccination.
3. Phase I: Proportion of participants experiencing an unsolicited AE up to 28 days post administration.
4. Phase I: Proportion of participants experiencing serious adverse events (SAEs), serious adverse reactions (SARs), suspected unexpected serious adverse reactions (SUSARs) and adverse events of special interest (AESI) respectively throughout the trial period.
5. Phase II: Crude variation of the mucosal humoral immune response specific to the vaccine N/S recombinant protein measured by ELISA (Geometric Mean Titers (±SD)) in each arm: IgA from nose swabs between D0 and D28.

Secondary endpoints 12

1. Crude variation of the mucosal humoral immune response specific to the vaccine N/S recombinant protein measured by ELISA (Geometric Mean Titers (±SD)): IgA from nose swabs between D0 and D7 (Phase I), D14, D28 (Phase I), M3, M6 and M12, respectively.
2. Neutralizing capacity of the mucosal humoral immune response specific to the vaccine N/S recombinant protein measured by PRNT and VLP assays at D0, D7 (Phase I), D14, D28, M3, M6, M12, respectively: Neutralizing Ig from nose swabs.
3. Crude variation of the systemic humoral immune response specific to the vaccine N/S recombinant protein measured by ELISA (Geometric Mean Titers (±SD)): Serum anti-S and anti-N IgG at D0, D7 (Phase I), D14, D28, M3, M6, M12, respectively.
4. Neutralizing capacity of the systemic humoral immune response specific to the vaccine N/S recombinant protein measured by PRNT and VLP assays at D0, D7 (Phase I), D14, D28, M3, M6, M12: Neutralizing serum IgG.
5. Percentage of responders against N and S antigens, respectively, measured by ELISpot SARS-CoV-2 assay at D0, D7 (Phase I) and D14, D28, M3, M6, M12: The quantification of IFN-gamma specifically secreted by T lymphocytes following exposure to N and S antigens will be performed on a subset of participants recruited only at Tours site for feasibility reasons. Phase I: 6 participants in each dose group. Phase II: 40 participants
6. Proportion of participants with COVID-19 infections confirmed by a positive PCR test or a positive antigen test between D0 and M12 in each arm.
7. Description of variant types identified on participants with a positive PCR test after vaccination.
8. Proportion of participants with serious COVID-19 infections defined as a hospitalization and/or death due to the COVID-19 between D0 and M12 in each arm.
9. Phase II: Proportion of participants experiencing an immediate AE within one hour following vaccine administration.
10. Phase II: Proportion of participants experiencing solicited local reactogenicity and systemic signs and symptoms for 7 days and 14 days respectively following vaccination.
11. Phase II: Proportion of participants experiencing an unsolicited AE up to 28 days post administration.
12. Phase II: Proportion of participants experiencing serious adverse events (SAEs), serious adverse reactions (SARs), suspected unexpected serious adverse reactions (SUSARs) and adverse events of special interest (AESI) respectively throughout the trial period.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Inserm

Sponsor organisation

Inserm

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Inserm

Contact name

Alizée PERROT

Public contact point

Organisation

Inserm

Contact name

Alizée PERROT

Centre Hospitalier Regional Universitaire De Tours

Sponsor organisation

Centre Hospitalier Regional Universitaire De Tours

Address

2 Boulevard Tonnelle

City

Tours

Postcode

37000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Regional Universitaire De Tours

Contact name

Zoha MAAKAROUN-VERMESSE

Public contact point

Organisation

Centre Hospitalier Regional Universitaire De Tours

Contact name

Mathilde SIGAUD-FILS

Sponsor responsibilities

Article 77 compliance

Inserm

Article 77 implementation

Inserm

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications