LVT-001 for COVID-19

Inclusion criteria

• {"criterion_text":"- Written informed consent obtained from the participant.\n- Has expressed interest and availability to meet the trial requirements.\n- 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.\n- 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).\n- Agree to stay in the geographical area of one of the clinical sites for the duration of the trial.\n- 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.\n- Agree to be registered in the computerized file of the Ministry of Health (VRB).\n- Be affiliated to French social security system.\n- Be male or female between the ages of ≥ 18 and ≤ 55 years for phase I and ≥ 18 and ≤ 60 years for phase II.\n- Good general health as determined at the discretion of the investigator (vital signs, medical history, and physical examination).\n- BMI: 18,5 kg/m² ≤ BMI ˂30kg/m².\n- 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."}

Exclusion criteria

• {"criterion_text":"- 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.\n- Illicit drug use within the past 12 months.\n- 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.\n- Received influenza vaccination within 14 days prior to trial vaccination, or any other licensed vaccine within 4 weeks prior to study vaccination.\n- Vaccination with a COVID-19 vaccine other than mRNA vaccine.\n- Known sensitivity to any of the ingredients of the trial vaccines.\n- Known allergic reaction to plastic.\n- Positive serology for hepatitis B (HBsAg), C (anti-HCV antibodies) and HIV 1-2.\n- 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.\n- Pregnancy positive test (βHCG test) or pregnancy or breastfeeding.\n- Received immunoglobulin or other blood products within three months prior to inclusion or planned administration before the trial completion.\n- Any form of contraindication to the trial vaccines tested.\n- 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.\n- 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).\n- 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).\n- History of severe psychiatric disorders that may affect participation in the trial.\n- Any other serious chronic illness requiring immediate monitoring by a hospital specialist.\n- 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.\n- Phase II only: Participants included in phase I will not be included in phase II.\n- Participants under legal protection (e.g., guardianship, tutorship).\n- History of chronic rhinitis, nasal septal defect, cleft palate, nasal polyps, or other nasal abnormality that might alter nasal mucosa and affect vaccine response.\n- A piercing or obstruction in the nostrils that could impede vaccine administration.\n- Previous nasal surgery or nasal cauterization.\n- History of frequent epistaxis.\n- Virologically documented (PCR or antigenic test) history of COVID-19 in the past 6 months.\n- Positive COVID-19 PCR test at screening visit.\n- Medical problems due to alcohol."}

Primary endpoints

• {"endpoint_text":"- Phase I: Proportion of participants experiencing an immediate AE within an hour and half following vaccine administration.","definition_or_measurement_approach":"Immediate adverse events assessed within 1.5 hours post-vaccination; outcome reported as proportion of participants experiencing an immediate AE."}
• {"endpoint_text":"- Phase I: Proportion of participants experiencing solicited local reactogenicity and systemic signs and symptoms for 7 days and 14 days respectively following vaccination.","definition_or_measurement_approach":"Solicited local and systemic reactogenicity recorded for specified windows (local: 7 days; systemic: 14 days) after vaccination; outcome reported as proportion of participants with solicited events."}
• {"endpoint_text":"- Phase I: Proportion of participants experiencing an unsolicited AE up to 28 days post administration.","definition_or_measurement_approach":"Unsolicited adverse events collected up to 28 days post-administration; outcome reported as proportion of participants with unsolicited AEs."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"SAEs, SARs, SUSARs and AESIs monitored throughout the trial period; outcomes reported as proportions of participants experiencing each event type."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Mucosal IgA measured from nasal swabs by ELISA; results summarized as Geometric Mean Titers (±SD) comparing D0 to D28 in each arm."}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Mucosal IgA measured on nose swabs by ELISA at specified timepoints; summarized as Geometric Mean Titers (±SD) over listed visits."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Neutralizing antibodies from nasal swabs assessed by PRNT and VLP assays at specified timepoints; outcome is neutralizing Ig measurements."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Serum anti-S and anti-N IgG measured by ELISA at specified timepoints; reported as Geometric Mean Titers (±SD)."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Serum neutralizing IgG assessed by PRNT and VLP assays at the listed timepoints; outcome is neutralizing antibody measurements."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Cellular response measured by ELISpot quantifying IFN-gamma-secreting T lymphocytes after exposure to N and S antigens on a subset (only Tours site); reported as percentage of responders at specified timepoints."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"COVID-19 infections identified by positive PCR or antigen test between D0 and M12; outcome reported as proportion of participants with confirmed infection per arm."}
• {"endpoint_text":"- Description of variant types identified on participants with a positive PCR test after vaccination.","definition_or_measurement_approach":"Sequencing/variant identification of SARS-CoV-2 on participants with positive PCR after vaccination; descriptive categorization of variant types."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Serious COVID-19 infections defined as hospitalization and/or death due to COVID-19 between D0 and M12; outcome reported as proportion per arm."}
• {"endpoint_text":"- Phase II: Proportion of participants experiencing an immediate AE within one hour following vaccine administration.","definition_or_measurement_approach":"Immediate adverse events assessed within 1 hour post-vaccination in Phase II; reported as proportion of participants experiencing an immediate AE."}
• {"endpoint_text":"- Phase II: Proportion of participants experiencing solicited local reactogenicity and systemic signs and symptoms for 7 days and 14 days respectively following vaccination.","definition_or_measurement_approach":"Solicited local (7 days) and systemic (14 days) reactogenicity recorded after vaccination in Phase II; reported as proportions."}
• {"endpoint_text":"- Phase II: Proportion of participants experiencing an unsolicited AE up to 28 days post administration.","definition_or_measurement_approach":"Unsolicited adverse events in Phase II collected up to 28 days post-administration; outcome reported as proportion with unsolicited AEs."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"SAEs, SARs, SUSARs and AESIs monitored throughout Phase II; outcomes reported as proportions."}

France

Earliest CTIS Part Ii Submission Date

02-01-2025

Latest Decision Or Authorization Date

05-09-2025

Processing Time Days

246

Number Of Sites

5

Number Of Participants

238

Primary sponsor

Full Name

Inserm

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France

Co-sponsors

• Centre Hospitalier Regional Universitaire De Tours