COVID-19 Immunization, Influenza Immunization
Conditions
Keywords
COVID-19 Vaccine and Influenza Vaccine
Brief summary
Study VBT00001 is planned to be a Phase 1/2, randomized, modified double-blind, active-controlled, multi-center study to be conducted in approximately 980 adults aged 50 years and older in the United States. The purpose of the study is to assess the safety and immunogenicity of IIV-HD (high-dose inactivated influenza vaccine) + rC19 (adjuvanted recombinant COVID-19 vaccine) vaccine comprised of IIV-HD combined with different recombinant Spike (rS) antigen levels of rC19 compared to IIV-HD alone, rC19 (dose 1) alone, and IIV-HD and rC19 (dose 1) (coadministered in opposite arms). Placebo will be coadministered in the IIV-HD alone, rC19 (dose 1) alone, and IIV-HD + rC19 study groups to control for the number of injections and to maintain observer-blinding. Thus, each participant will receive two injections at enrollment, one in each deltoid muscle. Study details include: * The study duration will be approximately 12 months * Study intervention will be administered via a single intramuscular (IM) injection into the right and left deltoid muscles on D01 * Dose escalation with sequential enrollment (sentinel cohort followed by main cohort for a given dose) * The visit frequency will be D01, D09 (telephone call), D30, D182 (telephone call), and D366 (telephone call) Number of Participants: Approximately 980 participants are expected to be randomized.
Interventions
BIOLOGICALIIV-HD
Inactivated, split-virion
BIOLOGICALrC19 (dose 1)
Protein subunit
BIOLOGICALIIV-HD + rC19 (dose 1)
IIV-HD component: Inactivated, split-virion rC19 component: Protein subunit
BIOLOGICALIIV-HD + rC19 (dose 2)
IIV-HD component: Inactivated, split-virion rC19 component: Protein subunit
BIOLOGICALIIV-HD + rC19 (dose 3)
IIV-HD component: Inactivated, split-virion rC19 component: Protein subunit
BIOLOGICALIIV-HD + rC19 (dose 4)
IIV-HD component: Inactivated, split-virion rC19 component: Protein subunit
OTHERPlacebo (0.9% NaCl)
Normal saline
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The study will be performed in a modified double-blind fashion. Modified double-blind: * Investigator, participants, and laboratory personnel will be blinded * Clinical site staff preparing/administering the study vaccines will be unblinded * Sponsor study staff will be blinded, except for dedicated staff involved in interim analysis, who will be unblinded at the time of interim analysis, and for dedicated staff involved in assessing criteria for safety surveillance
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Inclusion criteria to be checked at Screening Visit * Aged 50 years or older on the day of inclusion * Informed consent form has been signed and dated. * Able to attend all scheduled visits and to comply with all study procedures. * Participant must be able to receive an injection in the deltoid muscle of both arms. * Participant must have completed a primary vaccination series against SARS-CoV-2 and at least 1 booster with a locally authorized or approved COVID-19 vaccine. Inclusion criteria to be checked at Visit 1 (D01): * Aged 50 years or older on the day of inclusion * Participants who are healthy or with pre-existing stable condition (defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 12 weeks before enrollment), as determined by medical evaluation including medical history and physical examination. * A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: * Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, or surgically sterile. OR • Is of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to study intervention administration until at least 4 weeks after study intervention administration. A female participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) on the day of enrollment before the first dose of study intervention. * Informed consent form has been signed and dated. * Able to attend all scheduled visits and to comply with all study procedures. * Participant must be able to receive an injection in the deltoid muscle of both arms. * Participant must have completed a primary vaccination series against SARS-CoV-2 and at least 1 booster with a locally authorized or approved COVID-19 vaccine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| GMR of SARS-CoV-2 neutralizing titers ratio D30/D01 in all participants | At D01 and D30 | Individual SARS-CoV-2 neutralizing titers ratio D30/D01 |
| Number of MAAEs relating to predefined PIMDs that meet the criteria for SAEs | From D182 through 12 months following the last study vaccination | MAAEs relating to predefined PIMDs that meet the criteria for SAEs |
| Geometric mean (GM) of HAI titers in all participants | At D01 and D30 | HAI titers |
| Geometric mean ratio (GMR) HAI titers ratio D30/D01 in all participants | At D01 and D30 | Individual HAI titers ratio D30/D01 |
| GM of SARS-CoV-2 neutralizing titers in all participants | At D01 and D30 | SARS-CoV-2 neutralizing titers |
| Number of participants with immediate adverse events (AEs) | Within 30 minutes after each vaccination | Immediate adverse events are any unsolicited systemic adverse events reported in the 30 minutes after vaccination |
| Number of participants with solicited injection site reactions | Up to 7 each days after vaccination | Solicited injection site reactions include injection site pain, erythema and swelling |
| Number of participants with solicited systemic reactions | Up to 7 days after each vaccination | Solicited systemic reactions include fever, headache, fatigue, myalgia and chills |
| Number of participants with unsolicited AEs | Up to 28 days after each vaccination | Unsolicited (spontaneously reported) AEs, not fulfilling criteria for solicited adverse reactions |
| Number of participants with adverse events of special interest (AESIs) | Up to 180 days after each vaccination | AESIs |
| Number of participants with medical attended adverse events (MAAEs) | Up to 180 days after each vaccination | MAAEs |
| Number of MAAEs relating to predefined potential immune-mediated disease (PIMDs) | From D182 through 12 months following the last study vaccination | MAAEs relating to predefined PIMDs |
| Number of participants with serious adverse events (SAEs) | Up to 180 days after each vaccination | SAEs |
| Number of participants with related SAEs | From D182 through 12 months following the last study vaccination | Related SAEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with HAI titer ≥ 10 (1/dil) in all participants | At D01 and D30 | detectable HAI titer ≥ 10 (1/dil) |
| Percentage of participants with HAI titer ≥ 40 (1/dil) in all participants | At D01 and D30 | HAI titer ≥ 40 (1/dil) |
| Percentage of participants with seroresponse to SARS-CoV-2 in all participants | At D30 | Seroresponse to SARS-CoV-2 is defined by SARS-CoV-2 neutralizing titers ≥ 4-fold rise in SARS-CoV-2 neutralizing titers from D01 to D30 |
| Percentage of participants with seroconversion in all participants | At D30 | Seroconversion is defined by: HAI titer \< 10 \[1/dil\] at D01 and post-injection titer ≥ 40 \[1/dil\] at D30 or HAI titer ≥ 10 \[1/dil\] and a ≥ 4-fold increase in titer \[1/dil\] at D30 |
Countries
United States
Outcome results
None listed