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

Phase 1

Completed

Conditions: Healthy

Interventions: Biological: qIRV
Biological: RSVpreF+qIRV
Biological: RSVpreF + qIRV 1.0 mL formulation
Drug: Placebo
Biological: RSVpreF
Biological: RSVpreF + qIRV 0.5 mL formulation

Registration Number: NCT05788237

Lead Sponsor: Pfizer

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 508

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SSA Group 2: Sequential	qIRV	Sequential administration of qIRV (Visit 1) followed by RSVpreF (Visit 2)
SSA Group 1: Combination	RSVpreF+qIRV	Combination (RSVpreF + qIRV) (Visit 1) followed by placebo (Visit 2). RSVpreF and qIRV are administered as concomitantly but as individual injections.
SSA Group 1: Combination	Placebo	Combination (RSVpreF + qIRV) (Visit 1) followed by placebo (Visit 2). RSVpreF and qIRV are administered as concomitantly but as individual injections.
SSA Group 2: Sequential	RSVpreF	Sequential administration of qIRV (Visit 1) followed by RSVpreF (Visit 2)
SSB Group 1: Combination (RSVpreF + qIRV) 1.0-mL formulation	RSVpreF + qIRV 1.0 mL formulation	RSVpreF lyophilized cake reconstituted with water for injection and mixed with qIRV, yielding an injection volume of 1.0 mL
SSB Group 2: Combination (RSVpreF +qIRV) 0.5-mL formulation	RSVpreF + qIRV 1.0 mL formulation	RSVpreF lyophilized cake reconstituted with qIRV to yield an injection volume of 0.5 mL
SSB Group 2: Combination (RSVpreF +qIRV) 0.5-mL formulation	RSVpreF + qIRV 0.5 mL formulation	RSVpreF lyophilized cake reconstituted with qIRV to yield an injection volume of 0.5 mL

Primary Outcome Measures

Name	Time	Method
SSA: Percentage of Participants Reporting AEs Within 1 Month After Vaccination 2	SSA: Within 1 Month after Vaccination 2	An AE was defined as any untoward medical occurrence in a 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 (i.e. excluding local reactions and systemic events) were included.
SSA: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 1	SSA: From Day 1 to Day 7 after Vaccination 1	Local reactions included pain, redness and swelling at the injection site, recorded by participants in an electronic diary (e-diary). Pain at injection site was graded as mild: did not interfere with activity; moderate: interfered with activity; severe: prevented daily activity. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 centimeter (cm). Redness and swelling were graded as mild: 2.5 cm to 5.0 cm; moderate: greater than (\>) 5.0 cm to 10.0 cm; severe: \> 10 cm.
SSA: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 2	SSA: From Day 1 to Day 7 after Vaccination 2 (1 Month After Vaccination 1)	Local reactions included pain, redness and swelling at the injection site, recorded by participants in an e-diary. Pain at injection site was graded as mild: did not interfere with activity; moderate: interfered with activity; severe: prevented daily activity. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 cm. Redness and swelling were graded as mild: 2.5 cm to 5.0 cm; moderate: \> 5.0 cm to 10.0 cm; severe: \> 10 cm.
SSB: Percentage of Participants With Local Reactions Within 7 Days After Vaccination	SSB: From Day 1 to Day 7 after Vaccination	Local reactions included pain, redness and swelling at the injection site, recorded by participants in an e-diary. Pain at injection site was graded as mild: did not interfere with activity; moderate: interfered with activity; severe: prevented daily activity. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 cm. Redness and swelling were graded as mild: 2.5 cm to 5.0 cm; moderate: \> 5.0 cm to 10.0 cm; severe: \> 10 cm.
SSA: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 1	SSA: From Day 1 to Day 7 after Vaccination 1	Systemic events included fever, fatigue, headache, vomiting, nausea, diarrhea, chills, new/worsened muscle pain and new/worsened joint pain. These were recorded by participants in an e-diary. Fever defined as oral temperature \>=38.0 degrees Celsius (deg C) and categorized as mild: \>=38.0 to 38.4 deg C, moderate: \>38.4 to 38.9 deg C, severe: \>38.9 to 40.0 deg C. Vomiting categorized as mild: 1-2 times in 24 hours (h); moderate: \>2 times in 24h; severe: required intravenous (IV) hydration. Diarrhea categorized as mild: 2-3 loose stools in 24h; moderate: 4-5 loose stools in 24h; severe: 6 or more loose stools in 24h. Headache, fatigue, chills, new/worsened muscle pain and new/worsened joint pain were categorized as mild: didn't interfere with activity; moderate: some interference with activity; severe: prevented daily routine activity.
SSA: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 2	SSA: From Day 1 to Day 7 after Vaccination 2 (1 Month after Vaccination 1)	Systemic events included fever, fatigue, headache, vomiting, nausea, diarrhea, chills, new/worsened muscle pain and new/worsened joint pain. These were recorded by participants in an e-diary. Fever defined as oral temperature \>=38.0 deg C and categorized as mild: \>=38.0 to 38.4 deg C, moderate: \>38.4 to 38.9 deg C, severe: \>38.9 to 40.0 deg C. Vomiting categorized as mild: 1-2 times in 24h; moderate: \>2 times in 24h; severe: required IV hydration. Diarrhea categorized as mild: 2-3 loose stools in 24h; moderate: 4-5 loose stools in 24h; severe: 6 or more loose stools in 24h. Headache, fatigue, chills, new/worsened muscle pain and new/worsened joint pain were categorized as mild: didn't interfere with activity; moderate: some interference with activity; severe: prevented daily routine activity.
SSB: Percentage of Participants With Systemic Events Within 7 Days After Vaccination	SSB: From Day 1 to Day 7 After Vaccination	Systemic events included fever, fatigue, headache, vomiting, nausea, diarrhea, chills, new/worsened muscle pain and new/worsened joint pain. These were recorded by participants in an e-diary. Fever defined as oral temperature \>=38.0 deg C and categorized as mild: \>=38.0 to 38.4 deg C, moderate: \>38.4 to 38.9 deg C, severe: \>38.9 to 40.0 deg C. Vomiting categorized as mild: 1-2 times in 24h; moderate: \>2 times in 24h; severe: required IV hydration. Diarrhea categorized as mild: 2-3 loose stools in 24h; moderate: 4-5 loose stools in 24h; severe: 6 or more loose stools in 24h. Headache, fatigue, chills, new/worsened muscle pain and new/worsened joint pain were categorized as mild: didn't interfere with activity; moderate: some interference with activity; severe: prevented daily routine activity.
SSA: Percentage of Participants Reporting Adverse Events (AEs) Within 1 Month After Vaccination 1	SSA: Within 1 Month after Vaccination 1	An AE was defined as any untoward medical occurrence in a 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 (i.e. excluding local reactions and systemic events) were included.
SSB: Percentage of Participants Reporting AEs Throughout the Sub Study	SSB: From Day 1 of Vaccination up to 35 days of follow-up post Vaccination	An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were included.
SSA: Percentage of Participants Reporting Serious Adverse Events (SAEs) Throughout the Sub Study	SSA: From Day 1 (Vaccination 1) up to 35 days of follow-up post Vaccination 2 (Maximum up to 70 days)	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 and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event.
SSB: Percentage of Participants Reporting SAEs Throughout the Sub Study	SSB: From Day 1 of Vaccination up to 35 days of follow-up post Vaccination (Maximum up to 36 days)	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 and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event.
SSA: Geometric Mean Titer (GMT) and Geometric Mean Ratio (GMR) of Neutralizing Titers (NT) for Each RSV Subgroup (A or B) 1 Month After Vaccination With Combination RSVpreF + qIRV (Group 1) and RSVpreF Alone (Group 2)	SSA- For Group 1: 1 Month after Vaccination 1 (Day 1); For Group 2: 1 Month after Vaccination 2 (1 Month after Vaccination 1)	GMTs and associated 2-sided 95% CIs are reported as descriptive data. GMRs and associated 2-sided 95% CIs are reported in statistical analysis section of this outcome measure. GMR was the ratio of RSV subgroup A (RSV A) or RSV subgroup B (RSV B) neutralizing GMTs in the combination RSVpreF + qIRV group to that in the sequential-administration RSVpreF group.
SSA: GMT and GMR of Strain-Specific Hemagglutination Inhibition (HAI) Titers For 1 Month After Vaccination With Combination RSVpreF + qIRV (Group 1) and qIRV Alone (Group 2)	SSA- For Group 1: 1 Month after Vaccination 1 (Day 1); For Group 2: 1 Month after Vaccination 2 (1 Month after Vaccination 1)	GMTs and associated 2-sided 95% CIs are reported as descriptive data. GMRs and associated 2-sided 95% CIs are reported in statistical analysis section of this outcome measure. GMR was the ratio of each strain neutralizing GMTs in the combination RSVpreF + qIRV group to that in the sequential-administration RSVpreF group. The analysis was performed on the influenza strains: H1N1 A/Sydney, H3N2 A/Darwin, B/Austria, and B/Phuket.

Secondary Outcome Measures

Name	Time	Method
SSB: GMT and GMR of NT for Each RSV A or RSV B 1 Month After Vaccination	SSB: At 1 Month after Vaccination (Day 1)	GMTs and associated 2-sided 95% CIs are reported as descriptive data. GMRs and associated 2-sided 95% CIs are reported in statistical analysis section of this outcome measure. GMR was the ratio of RSV A or RSV B neutralizing GMTs in the combination of 1 mL RSVpreF + qIRV (group 1) and 0.5 ml of RSVpreF + qIRV (group 2)
SSB: GMTs of Strain-Specific Hemagglutination Inhibition (HAI) at 1 Month After Vaccination	SSB: At 1 Month after Vaccination (Day 1)	GMTs and associated 2-sided 95% CIs are reported as descriptive data. GMRs and associated 2-sided 95% CIs are reported in statistical analysis section of this outcome measure. GMR was the ratio of each strain neutralizing GMTs to the combination of 1 mL RSVpreF + qIRV (Group 1) and 0.5 ml of RSVpreF + qIRV (Group 2). The analysis was performed on the influenza strains: H1N1 A/Sydney, H3N2 A/Darwin, B/Austria, and B/Phuket.