Safety and Immunogenicity of Quadrivalent Influenza mRNA Vaccine MRT5407 in Adult Participants18 Years of Age and Older

• ClinicalTrials.gov Identifier: NCT05553301
• Recruitment Status: Active, not recruiting
• First Posted: September 23, 2022
• Last Update Posted: June 2, 2023
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Tracking Information

• First Submitted Date: September 20, 2022
• First Posted Date: September 23, 2022
• Last Update Posted Date: June 2, 2023
• Actual Study Start Date: October 3, 2022
• Estimated Primary Completion Date: January 19, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 20, 2022)

• Number of participants with immediate 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 and systemic reactions [ Time Frame: Up to 7 days after injection ]
  Adverse reactions pre-listed in the protocol and case report form (CRF) Injection site reactions: pain, redness, swelling, hardening, bruising Systemic reactions: fever, headache, malaise, 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 (MAAE)s [ Time Frame: Up to 28 days after injection ]
  AEs with a new onset or a worsening of a condition that prompts the participant or participant to seek unplanned medical advice at a physician's office or Emergency Department
• Number of participants with serious adverse events (SAEs) [ Time Frame: From Day one to Day 366 ]
  SAEs 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)
• Individual Hemagglutination inhibition (HAI) titer [ Time Frame: At Day 1 and Day 29 ]
  Antibody titers are expressed as GMTs at baseline and post-baseline
• Percentage of participants with detectable antibody HAI titers greater than or equal to (≥) 10 [1/dil] [ Time Frame: At Day 1 and Day 29 ]
• Individual HAI titer ratio [ Time Frame: At Day 1 and Day 29 ]
  Ratios of antibody titers measured by HAI in each group before and after vaccination
• Number of participants archiving HAI seroconversion against Antigens [ Time Frame: At Day 1 and Day 29 ]
  Number of participants with 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
• Percentage of participants with antibody HAI titers greater than or equal to (≥) 40 [1/dil] [ Time Frame: At Day 29 ]
• Percentage of participants with 2-fold and 4-fold rise in HAI titers [ Time Frame: At Day 1 and Day 29 ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 20, 2022)

• Neutralizing Ab titers [ Time Frame: At Day 1 and Day 29 ]
  Neutralizing Ab titers expressed as GMTs
• Individual neutralizing antibodies titer ratio [ Time Frame: At Day 1 and Day 29 ]
• Percentage of participants with 2-fold and 4-fold increase in neutralizing titers [ Time Frame: At Day 1 and Day 29 ]
• Individual HAI Ab titer ratio [ Time Frame: Day 1, Day 91, Day 181 and Day 366 ]
• Percentage of participants with antibody HAI titers greater than or equal to (≥) 40 [1/dil] [ Time Frame: At Day 91, Day 181 and Day 366 ]
• Individual neutralizing Ab titer ratio [ Time Frame: Day 1, Day 91, Day 181 and Day 366 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Immunogenicity of Quadrivalent Influenza mRNA Vaccine MRT5407 in Adult Participants18 Years of Age and Older
• Official Title: Safety and Immunogenicity of Quadrivalent Influenza mRNA Vaccine MRT5407 in Adults Aged 18 Years and Older
• Brief Summary: The purpose of this study is to evaluate the safety and immunogenicity of a single intramuscular (IM) injection of up to 2 dose levels of Quadrivalent Influenza messenger ribonucleic acid (mRNA) Vaccine MRT5407 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 is approximately 12 months.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Sentinel Cohort: Open label

Main Cohort:

• Open label (Sponsor, except laboratory testing personnel)
• Blinded (Sites, except for those preparing/administering study intervention)

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

This is a parallel-group prevention study with up to 5 arms that will be blinded to participants, investigators / sub-investigators, outcomes assessors, and laboratory personnel (with the exception of the sentinel safety portion of the study, which will be open-label). The Sponsor study staff will be unblinded (except laboratory testing personnel).

Primary Purpose: Prevention

• Condition: Influenza Immunization

Intervention

• Biological: Quadrivalent Influenza mRNA Vaccine MRT5407

  Pharmaceutical Form: Liquid frozen solution in a vial

  Route of Administration: Intramuscular Injection

• Biological: Quadrivalent Recombinant Influenza Vaccine

  Pharmaceutical Form: Liquid frozen solution in a vial

  Route of Administration: Intramuscular Injection

  Other Name: Flublok Quadrivalent®
• Biological: Quadrivalent Influenza Standard Dose Vaccine

  Pharmaceutical Form: Liquid suspension for injection in pre-filled syringe

  Route of Administration: Intramuscular Injection

  Other Name: Fluzone Qudrivalent®
• Biological: Quadrivalent Influenza High-Dose Vaccine

  Pharmaceutical Form: Liquid suspension for injection in pre-filled syringe

  Route of Administration: Intramuscular Injection

  Other Name: Fluzone High-Dose Quadrivalent®

Study Arms

• Experimental: Group 1: Quadrivalent Influenza mRNA Vaccine MRT5407 dose level 1
  participants will receive a single dose of QIV mRNA vaccine (dose level 1)
  Intervention: Biological: Quadrivalent Influenza mRNA Vaccine MRT5407
• Experimental: Group 2: Quadrivalent Influenza mRNA Vaccine MRT5407 dose level 2
  participants will receive a single dose of QIV mRNA vaccine (dose level 2)
  Intervention: Biological: Quadrivalent Influenza mRNA Vaccine MRT5407
• Active Comparator: Group 3: RIV4
  participants will receive a single dose of RIV4 vaccine
  Intervention: Biological: Quadrivalent Recombinant Influenza Vaccine
• Active Comparator: Group 4: QIV-SD
  participants will receive a single dose of QIV-SD vaccine
  Intervention: Biological: Quadrivalent Influenza Standard Dose Vaccine
• Active Comparator: Group 5: QIV-HD
  participants will receive a single dose of QIV -HD vaccine (for elderly only)
  Intervention: Biological: Quadrivalent Influenza High-Dose Vaccine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 20, 2022): 560
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 19, 2024
• Estimated Primary Completion Date: January 19, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Aged 18 years 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:

  • 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.

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)
• Previous history of myocarditis, pericarditis, and / or myopericarditis
• 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
• 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
• Self-reported or documented seropositivity for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus
• Receipt of any mRNA vaccine/product in the 2 months preceding study intervention administration

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT05553301
• Other Study ID Numbers: VAV00002; U1111-1271-1302 ( Registry Identifier: ICTRP )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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

• Current Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
• Original Responsible Party: Same as current
• Current Study Sponsor: Sanofi Pasteur, a Sanofi Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: May 2023