MUCOBOOST
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.
Topic
COVID-19 vaccine
Sponsor
University Hospital Center of Tours and Inserm – ANRS MIE
Coordinating investigator
Zoha MAAKAROUN-VERMESSE MD, PhD – Vaccinology Unit, CIC 1415, University Hospital Center of Tours
Short description
This Phase I/II trial in France evaluates safety and immunogenicity of a booster dose of an intranasal COVID-19 vaccine expressing SARS-CoV-2 N/S recombinant proteins (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 three escalating 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 participant in the Phase I, the go/no-go decision for Phase II and selection of the optimal dose will be performed.
Phase II will then evaluate the immunogenicity of the selected intranasal dose of LVT-001 vaccine, compared to the standard of care of intramuscular COVID-19 mRNA Pfizer-BioNTech booster.
Study design
This is a randomized, comparative, multicentric, open-label, dose-escalating phase I/II trial in France. The Pfizer-BioNTech mRNA vaccine chosen will be the authorized vaccine adapted to the variant circulating at the start of Phase II in France and recommended by regulatory authorities at the start of Phase II. In the case of a new variant, the mRNA vaccine version will be changed during the trial and newly enrolled participants will receive the most relevant and current version of the vaccine.
Phase I (first-in-human): 3 doses of the LVT-001 vaccine will be evaluated and a stratified, model-based dose escalation design will be used with 3 cohorts of 12 volunteers per dose level.
The first stratum will start at the lower dose and escalation rules will be applied.
Specific rules are established for the vaccination of the first six participants of each cohort, for the continuation of the vaccination of the last six participants within the cohort, and for dose escalation between each cohort.
Phase II: Open label, controlled, randomized Phase II comparing a booster dose of the selected dose of the LVT-001 vaccine to a booster dose of the standard of care (intramuscular COVID-19 mRNA Pfizer-BioNTech booster). The participants will be randomized 1:1 between:
- Experimental arm: one booster nasal spray of intranasal vaccine LVT-001, administered in each nostril at D0
- Control arm: one injection of the COVID-19 mRNA vaccine (Pfizer-BioNTech), as recommended at the start of Phase II in France, at D0
Primary objective
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.
Primary endpoint
Phase I:
- Proportion of participants experiencing an immediate adverse event (AE) within an hour and half following vaccine administration.
- Proportion of participants experiencing solicited local reactogenicity and systemic signs and symptoms for 7 days and 14 days respectively following vaccination.
- Proportion of participants experiencing an unsolicited AE up to 28 days post administration.
- 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 study period
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.
Study population
This trial will include healthy adult volunteers as this is a vaccine first-in-human trial. For the Phase II, adults above 60 years old will not be eligible due to risk of immuno-senescence.
Intervention
The investigational medicinal products are:
Phase I : Experimental vaccine: Intranasal recombinant protein vaccine LVT-001. The LVT-001 intranasal vaccine will be administered at D0 in each nostril
- Cohort A (12 participants): 20 μg (10 μg in each nostril)
- Cohort B (12 participants): 60 μg (30 μg in each nostril)
- Cohort C (12 participants): 120 μg (60 μg in each nostril)
Phase II
- Experimental vaccine: Intranasal recombinant protein vaccine LVT-001 at the selected dose. The LVT-001 intranasal vaccine will be administered at D0 in each nostril.
- Control vaccine: Intramuscular COVID-19 mRNA vaccine (Pfizer-BioNTech) recommended at the start of Phase II.
Number of subjects
A total of 36 and 202 healthy volunteers will be enrolled in Phase I and Phase II, respectively.
Participating country(ies) and sites
The trial will be conducted in Investigational Centers of the I-REIVAC Network.
- Two recruiting centers in France for phase I
- Five recruiting centers in France for phase II
Study duration
Expected enrolment duration: 6 months for phase I and 6 months for phase II
Duration of the trial for a participant: 13 months
Total expected duration of the trial: 3 years
Estimated date of completion of the trial: Q1 2028
Funding
AAP ReCH-MIE
UMS MART activities
Methodological aspects and statistical analysis