A Study to Examine Respiratory Combination Vaccines Against Respiratory Syncytial Virus (RSV) and Flu in Older Adults

Study Overview
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Brief Summary
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Substudy A: The study aims to learn about the safety and effects of two new vaccines for RSV (RSVpreF) and influenza (modRNA qIRV) when given as a single shot compared to when given separately. RSV and influenza lead to infections, mainly in the fall and winter. These vaccines are being developed to help prevent respiratory syncytial virus (RSV) and influenza (Flu) disease. This study is seeking participants who: are 60 years or older are healthy or have well-controlled chronic conditions have not had a flu shot in the last 120 days and agree to be present for all study visits, procedures, and blood draws. The participants will be divided into 2 groups. Group 1 will receive RSVpreF plus qIRV combo shot, after which participants will receive the placebo (a shot which has no medicine). Group 2 will receive shots for qIRV first and then RSVpreF 1 month apart. The investigators will examine the experiences of the participants receiving the study vaccines. This will help the investigators determine if the study vaccines are safe and produce a similar immune response. Participants will be involved in this study for 2 months. During this time, participants will have 3 visits at the study clinic. Substudy B will investigate 2 formulations of RSVpreF + qIRV of different volumes and osmolaities (concentrations). These formulations will be examined for safety, tolerability, and immunogenicity, with the goal of selecting a formulation for further study. This study is seeking participants who: are 50 years or older are healthy or have well-controlled chronic conditions have not had a flu shot in the last 180 days and agree to be present for all study visits, procedures, and blood draws. The participants will be divided into 2 groups. Group 1 will receive RSVpreF plus qIRV in a 1.0-mL formulation while Group 2 will receive RSVpreF plus qIRV in a 0.5-mL formulation. The investigators will examine the experiences of the participants receiving the study vaccines. This will help the investigators determine if the study vaccines are safe, well tolerated and produce a similar immune response. Participants will be involved in this study for 1 month. During this time, participants will have 2 visits at the study clinic.

Detailed Description
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Substudy A: This study is designed to evaluate the safety, tolerability, and immunogenicity of respiratory combination vaccine candidates. This initial study will be conducted as a Phase 1b, parallel-group, randomized, placebo-controlled, observer-blinded substudy of RSVpreF and a nucleoside-modified RNA vaccine (qIRV) against RSV and influenza when administered as a combined vaccine and when administered alone. Healthy adults ≥60 years of age will be randomized 1:1 to either Group 1: combination (RSVpreF + qIRV) followed by placebo; or Group 2: sequential administration of qIRV followed by RSVpreF administered 1 month apart. Substudy B will be conducted as a Phase 1b, parallel-group, randomized, observer-blinded substudy of RSVpreF and a nucleoside-modified RNA vaccine (qIRV) against RSV and influenza administered as a combined vaccine in a 1.0-mL formulation and when administered in a 0.5-mL formulation. Healthy adults ≥50 years of age will be randomized 1:1 to either Group 1: combination (RSVpreF + qIRV) 1.0-mL formulation; or Group 2: combination (RSVpreF + qIRV) 0.5 mL formulation. Approximately 100 participants will be randomized within the 50- through 64-year-old group, and 100 participants ≥65 years of age will be randomized.

Official Title
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A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Respiratory Combination Vaccine Candidates in Older Adults

Conditions
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Healthy

Intervention / Treatment
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* Biological: RSVpreF+qIRV
* Biological: qIRV
* Biological: RSVpreF
* Drug: Placebo
* Biological: RSVpreF + qIRV 1.0 mL formulation
* Biological: RSVpreF + qIRV 0.5 mL formulation


Participation Criteria
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Eligibility Criteria
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Substudy A: Inclusion Criteria: Participants ≥60 years of age at study enrollment. Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures. Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study. Capable of giving and having signed the informed consent as described in the protocol, which includes complying with the requirements and restrictions listed in the ICD and in this protocol. Receipt of licensed influenza vaccination for the 2022-2023 northern hemisphere season or 2022 southern hemisphere season >120 days before study intervention administration. Exclusion Criteria: A confirmed diagnosis of RSV infection or influenza ≤120 days before study intervention administration. History of severe adverse reaction associated with any vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s). Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate IM injection. Serious chronic disorder, including metastatic malignancy, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, or any other disorder that, in the investigator's opinion, excludes the participant from participating in the study. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Receipt of chronic systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids), or radiotherapy, within 60 days before study intervention administration, or planned receipt throughout the study. Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration, or planned receipt throughout the study. Receipt of any licensed RSV vaccine at any time prior to enrollment, or planned receipt throughout the study. Receipt of any licensed influenza vaccine ≤120 days before study enrollment, or planned receipt throughout the study. Participation in other studies involving an investigational RSV or mRNA influenza vaccine at any time prior to enrollment, and thereafter until study completion, regardless of vaccine assignment. Participation in any other interventional studies within 28 days before study enrollment through study completion. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members. Substudy B Inclusion Criteria: Participants ≥50 years of age at study enrollment. Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures. Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study. Capable of giving and having signed the informed consent as described in the protocol, which includes complying with the requirements and restrictions listed in the ICD and in this protocol. Receipt of licensed influenza vaccination for the 2022-2023 northern hemisphere season or 2022 southern hemisphere season >180 days before study intervention administration. Exclusion Criteria: A confirmed diagnosis of RSV infection or influenza ≤120 days before study intervention administration. History of severe adverse reaction associated with any vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s). Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate IM injection. Serious chronic disorder, including metastatic malignancy, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, or any other disorder that, in the investigator's opinion, excludes the participant from participating in the study. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Receipt of chronic systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids), or radiotherapy, within 60 days before study intervention administration, or planned receipt throughout the study. Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration, or planned receipt throughout the study. Receipt of any RSV vaccine at any time prior to enrollment, or planned receipt throughout the study. Receipt of any influenza vaccine ≤180 days before study enrollment, or planned receipt throughout the study. Participation in other studies involving an investigational RSV vaccine or mRNA influenza vaccine at any time prior to enrollment, and thereafter until study completion, regardless of vaccine assignment. Participation in any other interventional studies within 28 days before study enrollment through study completion. Participation in purely observational studies is acceptable. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Substudy A: Approximately 250 healthy adults ≥60 years of age will be randomized 1:1 to either Group 1: combination (RSVpreF + qIRV) (Visit 1) followed by placebo (Visit 2); or Group 2: sequential administration of qIRV (Visit 1) followed by RSVpreF (Visit 2) administered 1 month apart. Randomization will be stratified by 3 age groups (60-64, 65-79, and ≥80 years) within each study site. Substudy B: Approximately 200 healthy adults ≥50 years of age will be randomized 1:1 to either Group 1: combination (RSVpreF + qIRV) 1.0-mL formulation; or Group 2: combination (RSVpreF + qIRV) 0.5 mL formulation. Randomization will be stratified by 6 age/sex groups (female 50-64, female 65-79, and female ≥80 years; male 50-64, male 65-79, and male ≥80 years) within the study site.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SSA Group 1: Combination<br>Combination (RSVpreF + qIRV) (Visit 1) followed by placebo (Visit 2). RSVpreF and qIRV are administered as concomitantly but as individual injections. | Biological: RSVpreF+qIRV<br>* RSVpreF containing 2 stabilized RSV prefusion F antigens, in equal amounts from virus subgroups A and B combined with Quadrivalent influenza modRNA vaccine (qIRV) encoding HA of 4 strains as recommended for the influenza season (2 A strains, 2 B strains)<br>Drug: Placebo<br>* 0.9% saline for injection<br>|
| Experimental: SSA Group 2: Sequential<br>Sequential administration of qIRV (Visit 1) followed by RSVpreF (Visit 2) | Biological: qIRV<br>* Quadrivalent influenza modRNA vaccine (qIRV) encoding HA of 4 strains as recommended for the influenza season (2 A strains, 2 B strains)<br>* Other names: PF-07252220;Biological: RSVpreF<br>* RSVpreF containing 2 stabilized RSV prefusion F antigens, in equal amounts from virus subgroups A and B<br>* Other names: PF-06928316;|
| Experimental: SSB Group 1: Combination (RSVpreF + qIRV) 1.0-mL formulation<br>RSVpreF lyophilized cake reconstituted with water for injection and mixed with qIRV, yielding an injection volume of 1.0 mL | Biological: RSVpreF + qIRV 1.0 mL formulation<br>* RSVpreF containing 2 Stabilized RSV prefusion F antigens, in equal amounts from virus subgroups A and B plus qIRV Encoding HA of 4 strains as recommended for the influenza season (2 A strains and 2 B strains) plus sterile water as diluent for injection<br>* Other names: PF-07941314;|
| Experimental: SSB Group 2: Combination (RSVpreF +qIRV) 0.5-mL formulation<br>RSVpreF lyophilized cake reconstituted with qIRV to yield an injection volume of 0.5 mL | Biological: RSVpreF + qIRV 1.0 mL formulation<br>* RSVpreF containing 2 Stabilized RSV prefusion F antigens, in equal amounts from virus subgroups A and B plus qIRV Encoding HA of 4 strains as recommended for the influenza season (2 A strains and 2 B strains) plus sterile water as diluent for injection<br>* Other names: PF-07941314;Biological: RSVpreF + qIRV 0.5 mL formulation<br>* RSVpreF containing 2 Stabilized RSV prefusion F antigens, in equal amounts from virus subgroups A and B plus qIRV Encoding HA of 4 strains as recommended for the influenza season (2 A strains and 2 B strains)<br>* Other names: PF-07941314;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SSA, SSB: Percentage of participants reporting local reactions | Pain at the injection site, redness, and swelling | For up to 7 days following vaccination | 
| SSA, SSB: Percentage of participants reporting systemic events | Fever, fatigue, headache, vomiting, nausea, diarrhea, chills, new or worsened muscle pain, and new or worsened joint pain | For up to 7 days following vaccination | 
| SSA, SSB: Percentage of participants reporting adverse events | An AE is any untoward medical occurrence in a participant receiving investigational product without regard to possibility of causal relationship. AEs include both serious and non-serious adverse events. | SSA: For 1-month after each vaccination. SSB: Throughout study completion, an average of 1-month following vaccination | 
| SSA, SSB: Percentage of participants reporting serious adverse events | SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | SSA: For 1-month after each vaccination SSB: Through study completion, an average of 1-month following vaccination | 
| SSA: Geometric mean ratio (GMR) of neutralizing titers (NT) for each RSV subgroup (A or B) 1 month after vaccination with combination RSVpreF + qIRV compared to that with RSVpreF alone (sequential administration group, Visit 3) | GMR of NTs at 1 month after vaccination with the combination RSVpreF + qIRV compared to RSVpreF alone for each RSV subfamily (A or B) | 1-month after vaccination | 
| SSA: Geometric Mean Ratio (GMR) of strain-specific hemagglutination inhibition (HAI) titers 1 month after vaccination with combination RSVpreF + qIRV compared to that with qIRV alone (sequential administration group, Visit 2) | GMR of strain-specific HAI titers 1 month after vaccination with combination RSVpreF + qIRV compared to that with qIRV alone. | 1-month after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SSB: Geometric mean titers (GMTs) of neutralizing titers (NTs) at 1 month after vaccination with each combination RSVpreF + qIRV formulation | RSV A and RSV B neutralizing titers measured 1 month after vaccination with the RSVpreF +qIRV 1.0 mL formulation will be compared to the RSV A and RSV B neutralizing titers measured 1 month after vaccination with RSVpreF + qIRV 0.5 mL formulation. | 1-month after vaccination | 
| SSB: Geometric mean titers (GMTs) of strain-specific hemagglutination inhibition (HAI) at 1 month after vaccination with each combination RSVpreF + qIRV formulation | Strain specific GMTs measured 1 month after vaccination with the RSVpreF +qIRV 1.0 mL formulation will be compared to the GMTs measured 1 month after vaccination with the RSVpreF + qIRV 0.5 mL formulation. | 1-month after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Flu, Influenza, Vaccine, RNA vaccine, RSV, Respiratory Syncytial Virus, Combination vaccine, Vaccine osmolality