A Phase I/II Study to Investigate the Safety and Immunogenicity of Quadrivalent Influenza mRNA Vaccines MRT5421, MRT5424, and MRT5429 in Healthy Participants Aged 18 Years and Above
Overview
- Phase
- Phase 1
- Intervention
- Quadrivalent Influenza mRNA Vaccine MRT5421
- Conditions
- Influenza Immunization
- Sponsor
- Sanofi Pasteur, a Sanofi Company
- Enrollment
- 910
- Locations
- 20
- Primary Endpoint
- HAI Ab titer ≥ 40 (1/dil)
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and immunogenicity of a single intramuscular (IM) injection of different formulations of Quadrivalent Influenza Vaccine (QIV) messenger ribonucleic acid (mRNA) (MRT5421, MRT5424, and MRT5429) compared to an active control (QIV- standard dose (SD), QIV- high dose (HD) [adults ≥ 65 years of age only], or quadrivalent recombinant influenza vaccine (RIV4)) in adults 18 years of age and older.
Detailed Description
Study duration per participant is approximately 12 months. * Treatment duration: 1 injection of one of the 7 QIV mRNA or one of the controls * Dose escalation with sequential enrollment
Investigators
Eligibility Criteria
Inclusion Criteria
- •Aged from 18 years on the day of inclusion or aged from 21 years on the days of inclusion, depending on the countries.
- •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 postmenopausal 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 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 the 1st dose of study intervention
Exclusion Criteria
- •Participants are excluded from the study if any of the following criteria apply:
- •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 (eg, polyethylene glycol, polysorbate); history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances; any allergic reaction (eg, anaphylaxis) after administration of mRNA vaccine
- •Previous history of myocarditis, pericarditis, and / or myopericarditis
- •Known history of previous episodes of Gillian-Barre Syndrome (GBS), neuritis (including Bell's palsy), convulsions, encephalitis, transverse myelitis, and vasculitis
- •Participants with an ECG that is consistent with possible myocarditis or pericarditis or, in the opinion of the investigator, demonstrates clinically relevant abnormalities that may affect participant safety or study results
- •Self-reported thrombocytopenia, contraindicating Intramuscular vaccination based on Investigator's judgment
- •Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating Intramuscular vaccination based on Investigator's judgment
- •Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with study conduct or completion
- •Moderate or severe acute illness / infection (according to Investigator's judgment) or febrile illness (temperature ≥ 38.0°C \[≥ 100.4°F\]) on the day of vaccination. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided
Arms & Interventions
Quadrivalent Influenza mRNA Vaccine MRT5421 Dose 1
participants will receive a single dose of QIV mRNA vaccine MRT5421
Intervention: Quadrivalent Influenza mRNA Vaccine MRT5421
Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 1
participants will receive a single dose of QIV mRNA vaccine MRT5429
Intervention: Quadrivalent Influenza mRNA Vaccine MRT5429
Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 2
participants will receive a single dose of QIV mRNA vaccine MRT5429
Intervention: Quadrivalent Influenza mRNA Vaccine MRT5429
Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 3
participants will receive a single dose of QIV mRNA vaccine MRT5429
Intervention: Quadrivalent Influenza mRNA Vaccine MRT5429
Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 4
participants will receive a single dose of QIV mRNA vaccine MRT5429
Intervention: Quadrivalent Influenza mRNA Vaccine MRT5429
Quadrivalent Influenza mRNA Vaccine MRT5424 Dose 1
participants will receive a single dose of QIV mRNA vaccine MRT5424
Intervention: Quadrivalent Influenza mRNA Vaccine MRT5424
Quadrivalent Influenza mRNA Vaccine MRT5424 Dose 2
participants will receive a single dose of QIV mRNA vaccine MRT5424
Intervention: Quadrivalent Influenza mRNA Vaccine MRT5424
Quadrivalent Influenza SD Vaccine
participants will receive a single dose of QIV-SD vaccine
Intervention: Quadrivalent Influenza Standard Dose Vaccine
Quadrivalent Influenza HD Vaccine
participants will receive a single dose of QIV -HD vaccine (for adults ≥ 65 years of age only)
Intervention: Quadrivalent Influenza High-Dose Vaccine
Quadrivalent Influenza RIV4 Vaccine
participants will receive a single dose of RIV4 vaccine
Intervention: Quadrivalent Recombinant Influenza Vaccine
Outcomes
Primary Outcomes
HAI Ab titer ≥ 40 (1/dil)
Time Frame: Day 29
HAI Ab titer ≥ 40 (1/dil) at D29
Number of participants with immediate unsolicited systemic adverse events (AEs)
Time Frame: Within 30 minutes after injection
Unsolicited systemic AEs that occur within 30 minutes after vaccination
Number of participants with solicited injection site reactions
Time Frame: Up to 7 days after injection
Adverse reactions pre-listed in the protocol and case report form (CRF) Injection site reactions: Injection site pain, Injection site erythema, and Injection site swelling
Number of participants with solicited systemic reactions
Time Frame: Up to 7 days after injection
Adverse reactions pre-listed in the protocol and case report form (CRF) Systemic reactions: fever, headache, fatigue, myalgia, arthralgia, chills
Number of participants with unsolicited AEs
Time Frame: Up to 28 days after injection
AEs that do not fulfill the conditions of solicited reactions
Number of participants with medically attended adverse events (MAAEs)
Time Frame: Up to 180 days after injection
MAAEs reported up to 180 days after injection
Number of participants with serious adverse events (SAEs)
Time Frame: Throughout the study (approximately 12 months)
SAEs reported throughout the study
AESIs reported throughout the study
Time Frame: AESIs reported throughout the study (approximatley 12 months)
AESIs reported throughout the study (approximately 12 months)
Number of participants with adverse events of special interests (AESIs)
Time Frame: Throughout the study (approximately 12 months)
AESIs reported throughout the study
Number of participants with out-of-range biological test results
Time Frame: Up to 8 days after injection
Out-of-range biological test results (including shift from baseline values)
Geometric Mean Titer (GMT)
Time Frame: At Day 1 and Day 29
Hemagglutinin inhibition (HAI) antibody (Ab) titers at D01 and D29
Geometric Mean of individual Titer Ratio (GMTR)
Time Frame: At Day 1 and Day 29
Individual HAI Ab titer ratio D29/D01
Seroconversion
Time Frame: At Day 1 and Day 29
Number of participants with HAI Ab titer \< 10 \[1/dil\] at Day 1 and post-vaccination titer ≥ 40 \[1/dil\] at Day 29, or titer ≥ 10 \[1/dil\] at Day 1 and a ≥ 4-fold-rise in titer \[1/dil\] at Day 29
Secondary Outcomes
- Neutralizing Ab titers at D01 and D29(At Day 1 and Day 29)
- Individual neutralizing antibodies titer ratio(At Day 1 and Day 29)
- 2-fold and 4-fold increase in neutralizing titers(Day 1 through Day 29)