Clinical trial NCT05788237: A Study to Examine Respiratory Combination Vaccines Against Respiratory Syncytial Virus (RSV) and Flu in Older Adults
Official title: A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Respiratory Combination Vaccine Candidates in Older Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Flu
Influenza
Vaccine
RNA vaccine
RSV
Respiratory Syncytial Virus
Combination vaccine
Vaccine osmolality
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2023-03-28
Enrollment: 508
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: PREVENTION

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.

Eligibility criteria: Substudy A:

Inclusion Criteria:

1. Participants ≥60 years of age at study enrollment.
2. Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures.
3. 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.
4. 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.
5. 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:

1. A confirmed diagnosis of RSV infection or influenza ≤120 days before study intervention administration.
2. History of severe adverse reaction associated with any vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
3. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate IM injection.
4. 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.
5. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
6. 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.
7. 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.
8. Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration, or planned receipt throughout the study.
9. Receipt of any licensed RSV vaccine at any time prior to enrollment, or planned receipt throughout the study.
10. Receipt of any licensed influenza vaccine ≤120 days before study enrollment, or planned receipt throughout the study.
11. 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.
12. Participation in any other interventional studies within 28 days before study enrollment through study completion.
13. 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:

1. Participants ≥50 years of age at study enrollment.
2. Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures.
3. 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.
4. 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.
5. 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:

1. A confirmed diagnosis of RSV infection or influenza ≤120 days before study intervention administration.
2. History of severe adverse reaction associated with any vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
3. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate IM injection.
4. 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.
5. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
6. 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.
7. 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.
8. Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration, or planned receipt throughout the study.
9. Receipt of any RSV vaccine at any time prior to enrollment, or planned receipt throughout the study.
10. Receipt of any influenza vaccine ≤180 days before study enrollment, or planned receipt throughout the study.
11. 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.
12. Participation in any other interventional studies within 28 days before study enrollment through study completion. Participation in purely observational studies is acceptable.
13. 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.

Primary outcomes:
measure: SSA: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 1
timeFrame: SSA: From Day 1 to Day 7 after Vaccination 1
measure: SSA: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 2
timeFrame: SSA: From Day 1 to Day 7 after Vaccination 2 (1 Month After Vaccination 1)
measure: SSB: Percentage of Participants With Local Reactions Within 7 Days After Vaccination
timeFrame: SSB: From Day 1 to Day 7 after Vaccination
measure: SSA: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 1
timeFrame: SSA: From Day 1 to Day 7 after Vaccination 1
measure: SSA: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 2
timeFrame: SSA: From Day 1 to Day 7 after Vaccination 2 (1 Month after Vaccination 1)
measure: SSB: Percentage of Participants With Systemic Events Within 7 Days After Vaccination
timeFrame: SSB: From Day 1 to Day 7 After Vaccination
measure: SSA: Percentage of Participants Reporting Adverse Events (AEs) Within 1 Month After Vaccination 1
timeFrame: SSA: Within 1 Month after Vaccination 1
measure: SSA: Percentage of Participants Reporting AEs Within 1 Month After Vaccination 2
timeFrame: SSA: Within 1 Month after Vaccination 2
measure: SSB: Percentage of Participants Reporting AEs Throughout the Sub Study
timeFrame: SSB: From Day 1 of Vaccination up to 35 days of follow-up post Vaccination
measure: SSA: Percentage of Participants Reporting Serious Adverse Events (SAEs) Throughout the Sub Study
timeFrame: SSA: From Day 1 (Vaccination 1) up to 35 days of follow-up post Vaccination 2 (Maximum up to 70 days)
measure: SSB: Percentage of Participants Reporting SAEs Throughout the Sub Study
timeFrame: SSB: From Day 1 of Vaccination up to 35 days of follow-up post Vaccination (Maximum up to 36 days)
measure: 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)
timeFrame: SSA- For Group 1: 1 Month after Vaccination 1 (Day 1); For Group 2: 1 Month after Vaccination 2 (1 Month after Vaccination 1)
measure: 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)
timeFrame: SSA- For Group 1: 1 Month after Vaccination 1 (Day 1); For Group 2: 1 Month after Vaccination 2 (1 Month after Vaccination 1)
Secondary outcomes:
measure: SSB: GMT and GMR of NT for Each RSV A or RSV B 1 Month After Vaccination
timeFrame: SSB: At 1 Month after Vaccination (Day 1)
measure: SSB: GMTs of Strain-Specific Hemagglutination Inhibition (HAI) at 1 Month After Vaccination
timeFrame: SSB: At 1 Month after Vaccination (Day 1)
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: