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Substudy 01 - Safety and Immunogenicity of One Monovalent Modified mRNA Vaccine Encoding Influenza Hemagglutinin With LNP, in Adult Participants Aged 18 to 49 Years and 60 Years and Above

Primary Purpose

Influenza Immunization

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
H3 mRNA / LNP Vaccine
Quadrivalent recombinant influenza Vaccine (RIV4)
Sponsored by
Sanofi Pasteur, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Influenza Immunization

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Aged 18 years and above on the day of inclusion *Aged 18 years to 49 years or 60 years and above on the day of inclusion (substudy 01) 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) at the screening visit. Inclusion Criteria to be Checked at Visit 1 (Day 1) Participants are eligible for the study only if all of the following criteria are met: 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 first dose of study intervention. Exclusion Criteria: Previous vaccination against influenza in the previous 6 months with an investigational or marketed vaccine Any screening laboratory parameter with laboratory abnormalities that are greater than Grade 1 or deemed clinically significant in the opinion of the Investigator OR, any screening Liver Function Test (ALT, AST, Bilirubin) > 1.2x Upper Limit of Normal or any other screening laboratory parameter outside of the range of normal limits for age and gender Positive test for human immunodeficiency virus (HIV) antigen and/or antibodies (Abs), hepatitis B (HB) virus surface antigen (HBsAg), hepatitis B core antibodies (HBcAb), or hepatitis C virus antibodies (HCV Abs) 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 [PEG], 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 COVID-19 vaccine Previous history of myocarditis, pericarditis, and/or myopericarditis Screening electrocardiogram (ECG) or troponin value that is consistent with probable or possible myocarditis, pericarditis, and/or myopericarditis or screening ECG that 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 Alcohol, prescription drug, or substance abuse that, in the opinion of the Investigator, might interfere with the study conduct or completion Receipt of any vaccine in the 4 weeks preceding study enrollment or planned receipt of any vaccine in the 4 weeks following study intervention administration Receipt of any mRNA vaccine/product in the 2 months preceding study enrollment or planned receipt of any mRNA vaccine/product within the 2 months following study intervention administration Receipt of immune globulins, blood or blood-derived products in the past 3 months -Participation at the time of study enrollment (or in the 4 weeks preceding study enrollment or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure Previous vaccination against influenza in the previous 6 months with an investigational or marketed vaccine Exclusion criteria to be checked at Visit 1 Day 1: 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. The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Sites / Locations

  • Investigational Site Number :0360004
  • Investigational Site Number :0360001Recruiting
  • Investigational Site Number :0360002
  • Investigational Site Number :0360003
  • Investigational Site Number :8260002Recruiting
  • Investigational Site Number :8260001Recruiting
  • Investigational Site Number :8260004Recruiting
  • Investigational Site Number :8260003Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Active Comparator

Arm Label

Group 1: H3 mRNA /LNP dose 1

Group 2: H3 mRNA /LNP dose 2

Group 3: H3 mRNA /LNP dose 3

Group 4: H3 mRNA /LNP dose 4

Group 5: H3 mRNA /LNP dose 5

Group 6 (Control Group): RIV4 dose

Arm Description

Participants will receive one intramuscular (IM) dose of H3 mRNA/LNP at Day 01

Participants will receive one IM dose of H3 mRNA/LNP at Day 01

Participants will receive one IM dose of H3 mRNA/LNP at Day 01

Participants will receive one IM dose of H3 mRNA/LNP at Day 01

Participants will receive one IM dose of H3 mRNA/LNP at Day 01

Participants will receive one IM dose of RIV4 at Day 01

Outcomes

Primary Outcome Measures

Number of participants with immediate adverse events (AEs)
Unsolicited systemic AEs that occur 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
Number of participants with unsolicited adverse events
Unsolicited (spontaneously reported) adverse events not fulfilling criteria for solicited reactions
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)
Presence of serious adverse events (SAEs)
Number of participants experiencing SAEs
Presence of adverse events of special interest (AESIs)
Number of participants experiencing AESIs
Hemagglutination inhibition (HAI) antibody (Ab) response to homologous strain
Antibody are expressed as geometric mean titers (GMTs) at baseline and post-baseline
HAI titers at D01
Antibody titers are expressed as GMTs at baseline and post-baseline
HAI titers at D29
Antibody titers are expressed as GMTs at baseline and post-baseline
Individual HAI Ab titer ratio
Individual HAI Ab titer ratio will be calculated as: D29/D01
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)
2-fold and 4-fold rise in HAI titers from D01 to D29
Expressed as percentage post-baseline
Percentage of participants with detectable antibody HAI titers greater than or equal to (≥) 40 [1/dil]
Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers at Day 1
Nab titers at Day 1
Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers at Day 29
Nab titers at Day 29
Individual nab titer ratio
Individual nab titer ratio will be calculated as: D29/D01
2-fold and 4-fold increase in neutralizing Ab titers from D01 to D29
Expressed as percentage post-baseline

Secondary Outcome Measures

Full Information

First Posted
April 6, 2023
Last Updated
September 29, 2023
Sponsor
Sanofi Pasteur, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT05829356
Brief Title
Substudy 01 - Safety and Immunogenicity of One Monovalent Modified mRNA Vaccine Encoding Influenza Hemagglutinin With LNP, in Adult Participants Aged 18 to 49 Years and 60 Years and Above
Official Title
A Phase I, Parallel, Randomized, Active-controlled, Multi-center, Dose-escalation Study With Early Safety Data Reviews to Assess Safety and Immunogenicity of One Monovalent Modified Influenza mRNA Vaccine Encapsulated in LNP, in Adults Aged 18 to 49 Years and 60 Years and Above.
Study Type
Interventional

2. Study Status

Record Verification Date
September 30, 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 12, 2023 (Actual)
Primary Completion Date
February 23, 2024 (Anticipated)
Study Completion Date
February 23, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi Pasteur, a Sanofi Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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).
Detailed Description
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza Immunization

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
This study will be blinded to participants and sites (except for those preparing/administering study interventions. The sponsor will be unblinded.
Allocation
Randomized
Enrollment
225 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group 1: H3 mRNA /LNP dose 1
Arm Type
Experimental
Arm Description
Participants will receive one intramuscular (IM) dose of H3 mRNA/LNP at Day 01
Arm Title
Group 2: H3 mRNA /LNP dose 2
Arm Type
Experimental
Arm Description
Participants will receive one IM dose of H3 mRNA/LNP at Day 01
Arm Title
Group 3: H3 mRNA /LNP dose 3
Arm Type
Experimental
Arm Description
Participants will receive one IM dose of H3 mRNA/LNP at Day 01
Arm Title
Group 4: H3 mRNA /LNP dose 4
Arm Type
Experimental
Arm Description
Participants will receive one IM dose of H3 mRNA/LNP at Day 01
Arm Title
Group 5: H3 mRNA /LNP dose 5
Arm Type
Experimental
Arm Description
Participants will receive one IM dose of H3 mRNA/LNP at Day 01
Arm Title
Group 6 (Control Group): RIV4 dose
Arm Type
Active Comparator
Arm Description
Participants will receive one IM dose of RIV4 at Day 01
Intervention Type
Biological
Intervention Name(s)
H3 mRNA / LNP Vaccine
Intervention Description
Pharmaceutical Form: Suspension for injection Route of Administration: Intra-Muscular
Intervention Type
Biological
Intervention Name(s)
Quadrivalent recombinant influenza Vaccine (RIV4)
Other Intervention Name(s)
Flublok Quadravalent®
Intervention Description
Pharmaceutical Form: Solution for injection in a pre-filled syringe Route of Administration: Intra-Muscular
Primary Outcome Measure Information:
Title
Number of participants with immediate adverse events (AEs)
Description
Unsolicited systemic AEs that occur within 30 minutes after vaccination
Time Frame
Within 30 minutes after vaccination
Title
Number of participants with solicited injection site or systemic reaction
Description
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
Title
Number of participants with unsolicited adverse events
Description
Unsolicited (spontaneously reported) adverse events not fulfilling criteria for solicited reactions
Time Frame
Up to 28 days after injection
Title
Presence of out-of-range biological test results
Description
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
Title
Presence of serious adverse events (SAEs)
Description
Number of participants experiencing SAEs
Time Frame
Throughout Study (up to approximately Month 6)
Title
Presence of adverse events of special interest (AESIs)
Description
Number of participants experiencing AESIs
Time Frame
Throughout Study (up to approximately Month 6)
Title
Hemagglutination inhibition (HAI) antibody (Ab) response to homologous strain
Description
Antibody are expressed as geometric mean titers (GMTs) at baseline and post-baseline
Time Frame
Day 29
Title
HAI titers at D01
Description
Antibody titers are expressed as GMTs at baseline and post-baseline
Time Frame
Day 1
Title
HAI titers at D29
Description
Antibody titers are expressed as GMTs at baseline and post-baseline
Time Frame
Day 29
Title
Individual HAI Ab titer ratio
Description
Individual HAI Ab titer ratio will be calculated as: D29/D01
Time Frame
Day 1 through Day 29
Title
Number of Participants with Vaccine Response or Seroconversion
Description
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
Title
2-fold and 4-fold rise in HAI titers from D01 to D29
Description
Expressed as percentage post-baseline
Time Frame
Day 1 to Day 29
Title
Percentage of participants with detectable antibody HAI titers greater than or equal to (≥) 40 [1/dil]
Time Frame
Day 29
Title
Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers at Day 1
Description
Nab titers at Day 1
Time Frame
Day 1
Title
Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers at Day 29
Description
Nab titers at Day 29
Time Frame
Day 29
Title
Individual nab titer ratio
Description
Individual nab titer ratio will be calculated as: D29/D01
Time Frame
Day 1 through Day 29
Title
2-fold and 4-fold increase in neutralizing Ab titers from D01 to D29
Description
Expressed as percentage post-baseline
Time Frame
Day 1 to Day 29

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Aged 18 years and above on the day of inclusion *Aged 18 years to 49 years or 60 years and above on the day of inclusion (substudy 01) 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) at the screening visit. Inclusion Criteria to be Checked at Visit 1 (Day 1) Participants are eligible for the study only if all of the following criteria are met: 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 first dose of study intervention. Exclusion Criteria: Previous vaccination against influenza in the previous 6 months with an investigational or marketed vaccine Any screening laboratory parameter with laboratory abnormalities that are greater than Grade 1 or deemed clinically significant in the opinion of the Investigator OR, any screening Liver Function Test (ALT, AST, Bilirubin) > 1.2x Upper Limit of Normal or any other screening laboratory parameter outside of the range of normal limits for age and gender Positive test for human immunodeficiency virus (HIV) antigen and/or antibodies (Abs), hepatitis B (HB) virus surface antigen (HBsAg), hepatitis B core antibodies (HBcAb), or hepatitis C virus antibodies (HCV Abs) 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 [PEG], 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 COVID-19 vaccine Previous history of myocarditis, pericarditis, and/or myopericarditis Screening electrocardiogram (ECG) or troponin value that is consistent with probable or possible myocarditis, pericarditis, and/or myopericarditis or screening ECG that 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 Alcohol, prescription drug, or substance abuse that, in the opinion of the Investigator, might interfere with the study conduct or completion Receipt of any vaccine in the 4 weeks preceding study enrollment or planned receipt of any vaccine in the 4 weeks following study intervention administration Receipt of any mRNA vaccine/product in the 2 months preceding study enrollment or planned receipt of any mRNA vaccine/product within the 2 months following study intervention administration Receipt of immune globulins, blood or blood-derived products in the past 3 months -Participation at the time of study enrollment (or in the 4 weeks preceding study enrollment or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure Previous vaccination against influenza in the previous 6 months with an investigational or marketed vaccine Exclusion criteria to be checked at Visit 1 Day 1: 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. The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Trial Transparency email recommended (Toll free for US & Canada)
Phone
800-633-1610
Ext
option 6
Email
Contact-US@sanofi.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi Pasteur, a Sanofi Company
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number :0360004
City
Herston
State/Province
Queensland
ZIP/Postal Code
4006
Country
Australia
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :0360001
City
Morayfield
State/Province
Queensland
ZIP/Postal Code
4506
Country
Australia
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :0360002
City
Camberwell
State/Province
Victoria
ZIP/Postal Code
3124
Country
Australia
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :0360003
City
Adelaide
ZIP/Postal Code
5000
Country
Australia
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :8260002
City
Leicester
State/Province
Leicestershire
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :8260001
City
London
State/Province
London, City Of
ZIP/Postal Code
SW10 9NH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :8260004
City
London
State/Province
London, City Of
ZIP/Postal Code
W12 0HS
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :8260003
City
Sheffield
ZIP/Postal Code
S10 2JF
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

Substudy 01 - Safety and Immunogenicity of One Monovalent Modified mRNA Vaccine Encoding Influenza Hemagglutinin With LNP, in Adult Participants Aged 18 to 49 Years and 60 Years and Above

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