Safety and Immunogenicity of a Monovalent mRNA Vaccine Encoding Influenza Hemagglutinin in Adult Participants 18 Years of Age and Older

A Phase I, Parallel, Randomized, Active-controlled, Multi-center, Dose-escalation Study With Early Safety Data Reviews to Assess Safety and Immunogenicity of a Monovalent mRNA Vaccine Encoding Influenza Hemagglutinin in Adults 18 Years of Age and Older

The purpose of this study is to evaluate the safety and immunogenicity of a single intramuscular (IM) injection of different dose levels of messenger ribonucleic acid (mRNA) vaccine encoding influenza hemagglutinin compared to an active control quadrivalent recombinant influenza vaccine (RIV4) in adults 18 years of age and older. Study details include:

Study Duration: approximately 6 months Treatment Duration: 1 injection of mRNA vaccine encoding influenza hemagglutinin encoding influenza hemagglutinin or control.

Visit Frequency: Screening visit, Day 01, Day 02, Day 03, Day 09, Day 29, Day 91, Day 181

Study Overview

• Status: Completed
• Conditions: Influenza; Influenza Immunization
• Intervention / Treatment: Biological: Influenza Hemagglutinin mRNA vaccine; Biological: Quadrivalent Recombinant Influenza Vaccine

Detailed Description

Approximately 6 months

• Study Type: Interventional
• Enrollment (Actual): 388
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Rolling Hills Estates, California, United States, 90274
      • Peninsula Research Associates Site Number : 8400013
    • San Diego, California, United States, 92108
      • Optimal Research Site Number : 8400026
  • Florida
    • Coral Gables, Florida, United States, 33134
      • AMR Coral Gables/Miami, Formerly Clinical Research of South Florida, an AMR company (Clinic) Site Number : 8400004
    • Hollywood, Florida, United States, 33024
      • Research Centers of America Site Number : 8400003
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research, LLC Site Number : 8400016
  • Illinois
    • Peoria, Illinois, United States, 61614
      • AES Peoria Site Number : 8400017
  • Kansas
    • El Dorado, Kansas, United States, 67042
      • AMR El Dorado Site Number : 8400009
    • Newton, Kansas, United States, 67114
      • AMR - Newton Site Number : 8400005
    • Wichita, Kansas, United States, 67205
      • AMR Wichita West Site Number : 8400030
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • AMR Lexington Site Number : 8400014
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Benchmark Research Site Number : 8400010
  • Nebraska
    • Omaha, Nebraska, United States, 68112
      • Quality Clinical Research Site Number : 8400018
    • Omaha, Nebraska, United States, 68134
      • Velocity Clinical Research, Omaha Site Number : 8400007
  • New York
    • Vestal, New York, United States, 13850
      • Velocity Clinical Research Vestal Site Number : 8400033
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center - N Charleston Site Number : 8400008
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • AMR Knoxville Site Number : 8400027
  • Texas
    • Austin, Texas, United States, 78704
      • Elligo Health Research, Inc. Site Number : 8400035
    • Austin, Texas, United States, 78705
      • Benchmark Research - Austin Site Number : 8400006
    • Austin, Texas, United States, 78744
      • AES Austin Site Number : 8400021
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc. Site Number : 8400012

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Having given written informed consent prior to undertaking any study-related procedure. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply:
• Any subject who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sentinel cohort 1; 20 Participants in each age group will receive either Influenza hemagglutinin mRNA vaccine candidate dose 1 or dose 2 and half number of the participants in each age group also receiving the RIV4 control	Biological: Influenza Hemagglutinin mRNA vaccine; Pharmaceutical form:Solution for injection-Route of administration:IM injection; Biological: Quadrivalent Recombinant Influenza Vaccine; Pharmaceutical form:Solution for injection-Route of administration:IM injection; Other Names: Flublok Quadrivalent®; RIV4
Experimental: sentinel cohort 2; 20 Participants in each age group will receive either Influenza hemagglutinin mRNA vaccine candidate dose 3 or dose 4 and half number of the participants in each age group also receiving the RIV4 control	Biological: Influenza Hemagglutinin mRNA vaccine; Pharmaceutical form:Solution for injection-Route of administration:IM injection; Biological: Quadrivalent Recombinant Influenza Vaccine; Pharmaceutical form:Solution for injection-Route of administration:IM injection; Other Names: Flublok Quadrivalent®; RIV4
Experimental: sentinel cohort 3; 10 Participants in each age group will receive Influenza hemagglutinin mRNA vaccine candidate dose 5 with half of the participants in each age group also receiving the RIV4 control	Biological: Influenza Hemagglutinin mRNA vaccine; Pharmaceutical form:Solution for injection-Route of administration:IM injection; Biological: Quadrivalent Recombinant Influenza Vaccine; Pharmaceutical form:Solution for injection-Route of administration:IM injection; Other Names: Flublok Quadrivalent®; RIV4
Experimental: main cohort 1; 40 Participants in each age group will receive either Influenza hemagglutinin mRNA vaccine candidate dose 1 or dose 2 and half number of the participants in each age group also receiving the RIV4 control	Biological: Influenza Hemagglutinin mRNA vaccine; Pharmaceutical form:Solution for injection-Route of administration:IM injection; Biological: Quadrivalent Recombinant Influenza Vaccine; Pharmaceutical form:Solution for injection-Route of administration:IM injection; Other Names: Flublok Quadrivalent®; RIV4
Experimental: main cohort 2; 40 Participants in each age group will receive either Influenza hemagglutinin mRNA vaccine candidate dose 3 or dose 4 and half number of the participants in each age group also receiving the RIV4 control	Biological: Influenza Hemagglutinin mRNA vaccine; Pharmaceutical form:Solution for injection-Route of administration:IM injection; Biological: Quadrivalent Recombinant Influenza Vaccine; Pharmaceutical form:Solution for injection-Route of administration:IM injection; Other Names: Flublok Quadrivalent®; RIV4
Experimental: main cohort 3; 20 Participants in each age group will receive Influenza hemagglutinin mRNA vaccine candidate dose 5, and half number of the participants in each age group also receiving the RIV4 control	Biological: Influenza Hemagglutinin mRNA vaccine; Pharmaceutical form:Solution for injection-Route of administration:IM injection; Biological: Quadrivalent Recombinant Influenza Vaccine; Pharmaceutical form:Solution for injection-Route of administration:IM injection; Other Names: Flublok Quadrivalent®; RIV4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of any unsolicited systemic adverse events (AEs) reported in the 30 minutes after injection	Number of participants with unsolicited systemic immediate adverse events (AEs)	Within 30 minutes after injection
Presence of solicited injection site reactions (ie, pre listed in the participant's diary card [DC] and in the electronic case report form [eCRF]) occurring up to 7 days after injection	Number of participants with solicited injection site reactions	Up to 7 days after injection
Presence of solicited systemic reactions (ie, pre-listed in the participant's DC and in the eCRF) occurring up to 7 days after injection	Number of participants with solicited systemic reactions	Up to 7 days after injection
Presence of unsolicited AEs reported up to 28 days after injection	Number of participants with unsolicited AEs	Up to 28 days after injection
Presence of medically attended AEs (MAAEs) reported up to 28 days after injection	Number of participants with medically attended adverse events (MAAE)s	Up to 28 days after injection
Presence of serious adverse events (SAEs) and adverse events of special interest (AESIs) throughout the study	Number of participants with serious adverse events (SAEs)	From baseline up to 6 months
Presence of out-of-range biological test results (including shift from baseline values) up to 28 days after injection	Number of participants with out-of-range biological test results	Up to 28 days after injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemagglutination inhibition (HAI) antibody (Ab) titers to homologous H3 strain at D29, D91, and D181	Antibody titers are expressed as Geometric Mean Titers (GMTs)	At Day 29, Day 91, and Day 181
Individual HAI Ab titer ratio D29/D01, D91/D01, D91/D29, D181/D01, and D181/D29	Ratios of antibody titers measured by HAI in each group before and after vaccination	From baseline up to 6 months
HAI Ab titer ≥ 40 [1/dil] at D29, D91, and D181		At Day 29, Day 91 and Day 181
2-fold and 4-fold rise in HAI titers from D01 to D91 and D01 to D181		From Day 01 through Day 91 and Day 01 through Day 181
Neutralizing Ab titers to homologous H3 strain at D29, D91, and D181		At Day 29, Day 91, and Day 181
Individual neutralizing Ab titer ratio D29/D01, D91/D01, D91/D29, D181/D01, and D181/D29		From baseline up to 6 months
2-fold and 4-fold rise in neutralizing titers from D01 to D91 and D01 to D181		From Day 01 through Day 29 and Day 01 through Day 181
HAI Ab titers to selected heterologous H3 strains at D01, D29, D91, and D181		At Day 01, Day 29, D91 and D181
Neutralizing Ab titers to selected heterologous H3 strains at D01, D29, D91, and D181		At Day 01, Day 29, Day 91, and Day 181

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2022
• Primary Completion (Actual): February 17, 2023
• Study Completion (Actual): February 17, 2023

Study Registration Dates

• First Submitted: October 31, 2023
• First Submitted That Met QC Criteria: October 31, 2023
• First Posted (Actual): November 7, 2023

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Coagulants; Agglutinins; Vaccines; Hemagglutinins
• Other Study ID Numbers: VAV00018; U1111-1271-2001 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes