This is a Phase 1, parallel, randomized, active-controlled, multi-center, dose-esclation study with a Master Protocol design which will include several substudies that are developed to evaluate the safety and immunogenicity of different dose levels of modified messenger ribonucleic acid (mRNA) vaccines encoding full length hemagglutinin (HA) sequence of influenza virus encapsulated in lipid nanoparticles (LNPs) (hereafter referred to as HA mRNA vaccines) compared to control(s). The HA mRNA vaccine candidates and control(s) are presented in the substudy protocols. The aim is to generate clinical data across different substudies to provide learnings regarding the mRNA technology to support optimization of the mRNA platform including mRNA and LNP design and to support the decision of LNP and dose selection for future projects using mRNA technology. The purpose of this Substudy 01 is to evaluate the safety and immunogenicity of a single IM injection of up to 5 dose levels of a monovalent modified mRNA encoding the full-length HA sequence of A/Tasmania/503/2020 (H3N2) influenza virus encapsulated in LNP (hereafter referred to as H3 mRNA /LNP) administered as a single intramuscular (IM) injection in adults 18 to 49 years of age and 60 years of age and above, compared to the following active control: a quadrivalent recombinant influenza vaccine (RIV4).
The study duration per participant will be approximately 6 months with 1 injection of one of the different HA mRNA vaccines or control for each substudy and a dose-escalation with sequential enrollment (sentinel cohort followed by main cohort).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
159
Pharmaceutical Form: Suspension for injection Route of Administration: Intra-Muscular
Pharmaceutical Form: Solution for injection in a pre-filled syringe Route of Administration: Intra-Muscular
Investigational Site Number : 0360004
Herston, Queensland, Australia
Investigational Site Number : 0360001
Morayfield, Queensland, Australia
Investigational Site Number : 0360002
Camberwell, Victoria, Australia
Investigational Site Number : 0360003
Adelaide, Australia
Investigational Site Number : 8260002
Leicester, Leicestershire, United Kingdom
Investigational Site Number : 8260001
London, London, City of, United Kingdom
Investigational Site Number : 8260004
London, London, City of, United Kingdom
Investigational Site Number : 8260003
Sheffield, Sheffield, United Kingdom
Number of participants with immediate adverse events (AEs)
Unsolicited systemic AEs that occur within 30 minutes after vaccination
Time frame: Within 30 minutes after vaccination
Number of participants with solicited injection site or systemic reaction
Number of participants reporting Adverse reactions pre-listed in the protocol and case report form (CRF) * Injection site reactions: pain, redness, swelling * Systemic reactions: fever, headache, malaise, myalgia, arthralgia, chills
Time frame: Within 7 days from vaccination
Number of participants with unsolicited adverse events
Unsolicited (spontaneously reported) adverse events not fulfilling criteria for solicited reactions
Time frame: Up to 28 days after injection
Presence of out-of-range biological test results
Number of participants with biological safety assessment values out of normal range (as per the laboratory performing the test)
Time frame: At Day 3, Day 9 or Day 29
Presence of serious adverse events (SAEs)
Number of participants experiencing SAEs
Time frame: Throughout Study (up to approximately Month 6)
Presence of adverse events of special interest (AESIs)
Number of participants experiencing AESIs
Time frame: Throughout Study (up to approximately Month 6)
Hemagglutination inhibition (HAI) antibody (Ab) response to homologous strain
Antibody are expressed as geometric mean titers (GMTs) at baseline and post-baseline
Time frame: Day 29
HAI titers at D01
Antibody titers are expressed as GMTs at baseline and post-baseline
Time frame: Day 1
HAI titers at D29
Antibody titers are expressed as GMTs at baseline and post-baseline
Time frame: Day 29
Individual HAI Ab titer ratio
Individual HAI Ab titer ratio will be calculated as: D29/D01
Time frame: Day 1 through Day 29
Number of Participants with Vaccine Response or Seroconversion
Seroconversion (HAI Ab titer \< 10 \[1/dil\] at D01 and post-injection titer ≥ 40 \[1/dil\] at D29, or titer ≥ 10 \[1/dil\] at D01 and a ≥ 4-fold increase in titer \[1/dil\] at D29)
Time frame: Day 1 through Day 29
2-fold and 4-fold rise in HAI titers from D01 to D29
Expressed as percentage post-baseline
Time frame: Day 1 to Day 29
Percentage of participants with detectable antibody HAI titers greater than or equal to (≥) 40 [1/dil]
Time frame: Day 29
Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers at Day 1
Nab titers at Day 1
Time frame: Day 1
Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers at Day 29
Nab titers at Day 29
Time frame: Day 29
Individual nab titer ratio
Individual nab titer ratio will be calculated as: D29/D01
Time frame: Day 1 through Day 29
2-fold and 4-fold increase in neutralizing Ab titers from D01 to D29
Expressed as percentage post-baseline
Time frame: Day 1 to Day 29
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.