Influenza, Human
Conditions
Brief summary
The purpose of this study is to learn if modified RNA (modRNA) vaccines for the prevention of influenza are: * safe; and * how these vaccines produce an immune response in generally healthy adults. Immune response is the way the body protects itself against things it sees as harmful or foreign. RNA (also called ribonucleic acid) is one of two types of nucleic acid made by cells. RNA contains information that has been copied from DNA (the other type of nucleic acid). Cells make several different forms of RNA, and each form has a specific job in the cell. Many forms of RNA have functions related to making proteins. RNA is also the genetic material of some viruses instead of DNA. RNA can be made in the laboratory and used in research studies. Also called ribonucleic acid. Influenza is term used for flu illness. It is an infection caused by a virus that affects your mouth, nose, and throat. The study is seeking for participants who: * are at least 18 years of age * have not received an influenza vaccine within the last 6 months * are generally healthy This study will be divided into three sub-studies: Substudy A (SSA), Substudy B (SSB), and Substudy C (SSC). All participants, regardless of sub-study, will receive 1 dose of either of the following vaccines as an injection into their arm: * 1 of the modRNA influenza vaccines that is being studied; or * an approved influenza vaccine approved for use in their respective age group. Participants will be involved in this study for about 6 months. During this time, participants will have at least 3 clinic visits.
Interventions
BIOLOGICALInfluenza ModRNA Vaccine
Intramuscular injection
BIOLOGICALQuadrivalent Influenza Vaccine (QIV)
Intramuscular injection
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This study will be an observer-blinded and Sponsor-unblinded study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria Applies to all 3 substudies: * participants ≥18 years of age. * generally healthy participants. Substudy C ONLY: \- receipt of licensed influenza vaccination for the 2023-2024 flu season at least 6 months ago. Key
Exclusion criteria
All 3 substudies: * diagnosis of influenza (by clinical testing) in the last 6 months. * immunocompromised individuals with known or suspected immunodeficiency * receipt of any investigational or licensed influenza vaccines within 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SSA: Percentage of Participants With Local Reactions for up to 7 Days Following Vaccination | From Day 1 through Day 7 after study vaccination [Vaccination on Day 1] | Local reactions included pain at the injection site, redness and swelling and were recorded by participants in the electronic dairy (e-diary) or by investigators in case report form (CRF) after vaccination. All local reactions were graded based on center for biologics evaluation and research (CBER) toxicity guidelines as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 (potentially life-threatening). In this outcome measure, data is reported as percentage of participants with any local reaction of any grade. |
| SSB: Percentage of Participants With Local Reactions for up to 7 Days Following Vaccination | From Day 1 through Day 7 after study vaccination [Vaccination on Day 1] | Local reactions included pain at the injection site, redness and swelling and were recorded by participants in the e-diary or by investigators in CRF after vaccination. All local reactions were graded based on CBER toxicity guidelines as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 (potentially life-threatening). In this outcome measure, data is reported as percentage of participants with any local reaction of any grade. |
| SSC: Percentage of Participants With Local Reactions for up to 7 Days Following Vaccination | From Day 1 through Day 7 after study vaccination [Vaccination on Day 1] | Local reactions included pain at the injection site, redness and swelling and were recorded by participants in the e-diary or by investigators in CRF after vaccination. All local reactions were graded based on CBER toxicity guidelines as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 (potentially life-threatening). In this outcome measure, data is reported as percentage of participants with any local reaction of any grade. |
| SSA: Percentage of Participants With Systemic Events for up to 7 Days Following Vaccination | From Day 1 through Day 7 after study vaccination [Vaccination on Day 1] | Systemic events (fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain and joint pain) were recorded by participants in the e-diary or by investigators in CRF after vaccination. All systemic events were graded based on CBER toxicity guidelines as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 (potentially life-threatening). In this outcome measure, data is reported as percentage of participants with any systemic events of any grade. |
| SSB: Percentage of Participants With Systemic Events for up to 7 Days Following Vaccination | From Day 1 through Day 7 after study vaccination [Vaccination on Day 1] | Systemic events (fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain and joint pain) were recorded by participants in the e-diary or by investigators in CRF after vaccination. All systemic events were graded based on CBER toxicity guidelines as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 (potentially life-threatening). In this outcome measure, data is reported as percentage of participants with any systemic events of any grade. |
| SSC: Percentage of Participants With Systemic Events for up to 7 Days Following Vaccination | From Day 1 through Day 7 after study vaccination [Vaccination on Day 1] | Systemic events (fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain and joint pain) were recorded by participants in the e-diary or by investigators in CRF after vaccination. All systemic events were graded based on CBER toxicity guidelines as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 (potentially life-threatening). In this outcome measure, data is reported as percentage of participants with any systemic events of any grade. |
| SSA: Percentage of Participants With Adverse Events (AEs) From Vaccination Through 4 Weeks After Vaccination | From study vaccination on Day 1 through 4 weeks after study vaccination | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Only AEs collected by non-systematic assessment (excluding local reactions and systematic events) were included in this outcome measure. |
| SSB: Percentage of Participants With AEs From Vaccination Through 4 Weeks After Vaccination | From study vaccination on Day 1 through 4 weeks after study vaccination | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Only AEs collected by non-systematic assessment (excluding local reactions and systematic events) were included in this outcome measure. |
| SSC: Percentage of Participants With AEs From Vaccination Through 4 Weeks After Vaccination | From study vaccination on Day 1 through 4 weeks after study vaccination | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Only AEs collected by non-systematic assessment (excluding local reactions and systematic events) were included in this outcome measure. |
| SSA: Percentage of Participants With SAEs From Vaccination Through 6 Months After Vaccination | From study vaccination on Day 1 through 6 months after study vaccination | An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, any other pre-specified criteria in protocol of the study or other important medical event judged by the investigator. |
| SSB: Percentage of Participants With SAEs From Vaccination Through 6 Months After Vaccination | From study vaccination on Day 1 through 6 months after study vaccination | An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, any other pre-specified criteria in protocol of the study or other important medical event judged by the investigator. |
| SSC: Percentage of Participants With SAEs From Vaccination Through 6 Months After Vaccination | From study vaccination on Day 1 through 6 months after study vaccination | An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, any other pre-specified criteria in protocol of the study or other important medical event judged by the investigator. |
| SSA: Percentage of Participants With Medically Attended Adverse Events (MAEs) From Vaccination Through 6 Months After Vaccination | From study vaccination on Day 1 through 6 months after study vaccination | An MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. |
| SSB: Percentage of Participants With MAEs From Vaccination Through 6 Months After Vaccination | From study vaccination on Day 1 through 6 months after study vaccination | An MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. |
| SSC: Percentage of Participants With MAEs From Vaccination Through 6 Months After Vaccination | From study vaccination on Day 1 through 6 months after study vaccination | An MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. |
| SSA: Percentage of Participants With Newly Diagnosed Chronic Medical Conditions (NDCMCs) From Vaccination Through 6 Months After Vaccination | From study vaccination on Day 1 through 6 months after study vaccination | An NDCMC was defined as a disease or medical condition, not previously identified, that was expected to be persistent or otherwise long-lasting in its effects (e.g., asthma). |
| SSB: Percentage of Participants With NDCMCs From Vaccination Through 6 Months After Vaccination | From study vaccination on Day 1 through 6 months after study vaccination | An NDCMC was defined as a disease or medical condition, not previously identified, that was expected to be persistent or otherwise long-lasting in its effects (e.g., asthma). |
| SSC: Percentage of Participants With NDCMCs From Vaccination Through 6 Months After Vaccination | From study vaccination on Day 1 through 6 months after study vaccination | An NDCMC was defined as a disease or medical condition, not previously identified, that was expected to be persistent or otherwise long-lasting in its effects (e.g., asthma). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SSA: Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition Assay (HAI) Titers at Baseline and 4 Weeks After Vaccination | Baseline (before study vaccination on Day 1), 4 weeks after study vaccination | GMTs and the corresponding 2-sided 95% confidence intervals (CIs) were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). |
| SSA: Geometric Mean Fold Rise (GMFR) of Strain-Specific HAI Titers From Before Vaccination to 4 Weeks After Vaccination | From before study vaccination on Day 1 up to 4 weeks after study vaccination | GMFR was defined as the geometric mean of the fold rise in the assay results from before vaccination to a specified time point after vaccination. |
| SSA: Percentage of Participants Achieving HAI Seroconversion for Each Strain at 4 Weeks After Vaccination | 4 weeks after study vaccination | Seroconversion was defined as an HAI titer \<1:10 prior to vaccination and \>=1:40 at the time point of interest, or an HAI titer of \>=1:10 prior to vaccination with at least a 4-fold rise at the time point of interest. |
| SSA: Percentage of Participants With HAI Titers >=1:40 For Each Strain at Baseline and 4 Weeks After Vaccination | Baseline (before study vaccination on Day 1), 4 weeks after study vaccination | This measure is for percentage of participants achieving HAI titers \>=1:40 for each strain. |
| SSB: GMTs of Strain-Specific HAI Titers at Baseline and 4 Weeks After Vaccination | Baseline (before study vaccination on Day 1), 4 weeks after study vaccination | — |
| SSB: GMFRs of Strain-Specific HAI Titers From Before Vaccination to 4 Weeks After Vaccination | From before study vaccination on Day 1 up to 4 weeks after study vaccination | — |
| SSB: Percentage of Participants Achieving HAI Seroconversion for Each Strain at 4 Weeks After Vaccination | 4 weeks after study vaccination | — |
| SSB: Percentage of Participants With HAI Titers >=1:40 For Each Strain at Baseline and 4 Weeks After Vaccination | Baseline (before study vaccination on Day 1), 4 weeks after study vaccination | This measure is for percentage of participants achieving HAI titers \>=1:40 for each strain. |
Countries
United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Participant flow
Recruitment details
This study was conducted across 3 sub studies: Substudy A (SSA), Substudy B (SSB) and Substudy C (SSC). A total of 1202 participants (SSA = 481; SSB = 450; SSC =271) were enrolled. Each participant was enrolled in only one substudy and randomized to a single study group.
Pre-assignment details
Dose levels for nucleoside-modified ribonucleic acid (modRNA) vaccines are in numerical order from lowest to highest total modRNA dose, i.e., dose level 1 represents the lowest total modRNA dose and dose level 7 represents the highest total modRNA dose. Trivalent modRNA vaccines identified as formulation 3 encode for additional influenza strain-specific antigens.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 60.4 Years STANDARD_DEVIATION 15.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 78 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 217 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 905 Participants |
| Sex: Female, Male Female | 62 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 96 | 0 / 96 | 0 / 96 | 0 / 97 | 0 / 94 | 0 / 90 | 0 / 87 | 0 / 90 | 0 / 89 | 0 / 94 | 0 / 30 | 0 / 30 | 0 / 30 | 0 / 30 | 0 / 30 | 0 / 30 | 0 / 31 | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 88 / 96 | 84 / 96 | 86 / 96 | 82 / 97 | 63 / 94 | 76 / 90 | 67 / 87 | 68 / 90 | 47 / 89 | 50 / 94 | 24 / 30 | 19 / 30 | 25 / 30 | 25 / 30 | 26 / 30 | 27 / 30 | 24 / 31 | 17 / 30 | 17 / 30 |
| serious Total, serious adverse events | 2 / 96 | 0 / 96 | 0 / 96 | 0 / 97 | 0 / 94 | 0 / 90 | 4 / 87 | 4 / 90 | 3 / 89 | 2 / 94 | 0 / 30 | 0 / 30 | 0 / 30 | 2 / 30 | 0 / 30 | 1 / 30 | 1 / 31 | 0 / 30 | 0 / 30 |
Outcome results
None listed