This Phase I/II trial in France evaluates safety and immunogenicity of a booster dose ofan intranasal COVID-19 vaccine (LVT-001) versus a booster dose of a COVID-19 mRNA vaccine(Pfizer-BioNTech) in healthy adult volunteers.As a first-in-human trial, Phase I will assess the safety and immunogenicity of threeescalating doses of the LVT-001 vaccine across 3 cohorts of 12 volunteers per dose level.Based on cumulative data collected up to Day 28 visit from the last included participantin the Phase I, the go/no-go decision for Phase II and selection of the optimal dose willbe performed.Phase II will then evaluate the immunogenicity of the selected intranasal dose of LVT-001vaccine, compared to the standard of care of intramuscular COVID-19 mRNA Pfizer-BioNTechbooster.
This is a randomized, comparative, multicenter, open-label, phase I/II trial in France
evaluating the safety and immunogenicity of a booster dose of an intranasal COVID-19
vaccine (LVt-001) versus a booster dose of a COVID-19 mRNA vaccine (Pfizer-BioNTech) in
healthy adult volunteers.
Phase I dose escalating - Primary Objective: To evaluate the safety of three escalating
doses of a boost of an intranasal COVID-19 vaccine (LVT-001) expressing SARS-CoV-2 N/S
recombinant protein in healthy volunteers.
Phase II superiority trial - Primary Objective: To evaluate, using nasal swabs, the
superiority of a booster dose of the selected intranasal COVID-19 vaccine (LVT-001)
expressing SARS-COV-2 N/S recombinant protein versus a booster dose of the intramuscular
COVID-19 mRNA vaccine (Pfizer-BioNTech) in healthy adult volunteers in term of mucosal
humoral immune response at Day 28.
Trial population: A total of 36 and 202 healthy volunteers will be enrolled in Phase I
and Phase II, respectively.
Interventions:
Phase I: The investigational medicinal product is the intranasal recombinant protein
vaccine LVT-001 administered at Day 0 in each nostril:
- Cohort A (12 participants): 20 µg
- Cohort B (12 participants): 60 µg
- Cohort C (12 participants): 120 µg
Phase II: Two investigational medicinal products will be compared:
- The selected dose of the intranasal recombinant protein vaccine LVT-001,
administered at Day 0 in each nostril.
- The intramuscular COVID-19 mRNA vaccine (Pfizer-BioNTech), administered as the
standard of care booster.
Expected Outcomes and Safety Considerations:
In Phase I, healthy participants are not expected to benefit directly from the trial
aside from the potential theoretical benefit of a mucosal immune response against
SARS-CoV-2. Currently, no clinical trial data exist for a nasal protein vaccine in
humans.
The anticipated risks primarily include local nasal reactions and systemic reactions
similar to those observed with other vaccines. Any adverse events following vaccination
are expected to be manageable with routine care, as determined by investigators.
Given that this is the first human trial of a nasal protein vaccine, the dose-escalation
design ensures a safety margin, allowing for careful monitoring before progressing to the
next cohort.
Biological: LVT-001
Intranasal administration
Biological: Cormirnaty
Intramuscular administration
Inclusion Criteria:
1. Written informed consent obtained from the participant.
2. Be male or female between the ages of:
1. ≥ 18 and ≤ 55 years for phase I
2. ≥ 18 and ≤ 60 years for phase II.
3. Good general health as determined at the discretion of the investigator (vital
signs, medical history, and physical examination).
4. BMI: 18,5 Kg/m2 ≤ BMI ˂30Kg/m2.
5. 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.
6. Has expressed interest and availability to meet the trial requirements.
7. 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.
8. 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).
9. Agree to stay in the geographical area of one of the clinical sites for the duration
of the trial.
10. 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.
11. Agree to be registered in the computerized file of the Ministry of Health (VRB).
12. Be affiliated to French social security system.
Exclusion Criteria:
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 3
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
routine 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. Participants included in phase I will not be included in phase II.
27. Participants under legal protection (e.g., guardianship, tutorship).
CHU Dijon Bourgogne - Centre d'Investigation Clinique 1432
Dijon, France
HCL - Hôpital de la Croix-Rousse - Service des Maladies Infectieuses et Tropicales
Lyon, France
APHP - Hôpital Cochin - Centre d'Investigation Clinique de Vaccinologie Cochin-Pasteur 1417
Paris, France
CHU de Saint-Etienne - Service des Maladies Infectieuses
Saint Priest en Jarez, France
CHRU de Tours - Centre d'Investigation Clinique 1415
Tours, France
Alizée PERROT
0033153948074
cdp.clinique@anrs.fr
Yoann DESVIGNES
0033247474632
cpcq@chu-tours.fr