Healthy Volunteers, Influenza Immunization
Conditions
Brief summary
This is a Phase I, first-in-human, randomized, modified double-blind, active-controlled, dose-escalation study to assess the safety and immunogenicity of up to 3 dose levels of mRNA NA vaccines, administered as a single IM injection in healthy adults aged 18 years and older. Two age groups, 18 to 64 years and ≥65 years, will be included in this study.
Detailed description
This study will include a screening visit, 6 study visits occurring on Days 1, 3, 9, 29, 91, and 181, and a safety follow-up telephone call on Day 366.
Interventions
BIOLOGICALmRNA NA vaccine
Pharmaceutical form: Suspension for injection Route of administration: Intramuscular
BIOLOGICALHigh Dose Quadrivalent Influenza Vaccine
Pharmaceutical form: Suspension for injection Route of administration: Intramuscular
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
This study will be blinded to participants, investigators/sub-investigators, outcomes assessors, laboratory personnel, and the sponsor study staff (with the exception noted for study staff involved in the ESDRs). Study staff involved in the ESDRs will be unblinded to group assignment of participants in the sentinel safety cohorts. After the ESDRs are performed for the sentinel safety cohorts, the SMT will continue monitoring the safety aspects of the study as part of blinded periodic safety reviews. Those preparing/administering the study interventions will be unblinded.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Aged 18 years or older on the day of inclusion. * A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: 1. Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be postmenopausal for at least 1 year, or surgically sterile OR 2. 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 12 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) within 8 hours before administration of study intervention. * Informed consent form has been signed and dated.
Exclusion criteria
* Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months). * Known systemic hypersensitivity to any of the study intervention components; history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances * Moderate or severe acute illness/infection (according to investigator judgement) or febrile illness (temperature ≥100.4°F) on the day of study intervention administration. * Have known or recently active (12 months) neoplastic disease or a history of any hematologic malignancy. * Have any diagnosis, current or past, of autoimmune disease. * Body mass index of 40 kg/m2 or higher. * Receipt of immune globulins, blood, or blood-derived products in the past 3 months. * Have taken high-dose inhaled corticosteroid (≥500 μg of fluticasone) within 6 months prior to study vaccination. * Self-reported or documented seropositivity for HIV, hepatitis B virus, or hepatitis C virus.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with clinically significant changes in clinical laboratory tests | From Day 1 to Day 8 | Laboratory tests include hematology: complete blood count (CBC) with differential, platelet count, coagulation panel (prothrombin time and PTT) and serum chemistry: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total and fractionated bilirubin, C-reactive protein, serum creatinine, and blood urea nitrogen |
| Number of participants with solicited injection site or systemic reaction | From Day 1 to Day 8 | — |
| Number of participants with unsolicited adverse events | From Day 1 to Day 29 | Unsolicited (spontaneously reported) adverse events not fulfilling criteria for solicited reactions |
| Number of participants with serious adverse events | From Day 1 to Day 366 | Serious adverse events are collected throughout the study |
| Number of participants with adverse events of special interest | From Day 1 to Day 366 | Adverse events of special interest are collected throughout the study |
| Number of participants with immediate adverse events | Within 30 minutes after vaccination | Immediate adverse events are unsolicited systemic adverse events reported in the 30 minutes after vaccination |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Individual Neuraminidase inhibition (NAI) titer | Day 1 and Day 29 | Antibody titers are expressed as GMTs at baseline and post-baseline |
| 2-fold and 4-fold rise in NAI antibody titers | From Day 1 to Day 29 | Expressed as percentage post-baseline |
| Percentage of participants with detectable antibody titers greater than or equal to (≥) 10 [1/dil] | Day 1 and Day 29 | Expressed as percentage at baseline and post-baseline |
| Neuraminidase inhibition (NAI) Antibodies at Day 1 and 29 | Day 1 and 29 | Antibody are expressed as GMTs at baseline and post-baseline |
Countries
United States
Outcome results
None listed