Safety and Immunogenicity of RSVpreF Coadministered With SIIV in Adults ≥65 Years of Age

Pfizer1,471 enrolled

Overview

The purpose of this study is to assess the safety and immunogenicity of RSVpreF when coadministered with SIIV compared to sequential administration of the vaccines when given 1 month apart (SIIV followed by RSVpreF). Additionally, the study will contribute data supporting the development of RSVpreF as a prophylactic vaccine against RSV disease in infants through maternal immunization and in older adults through active vaccination.

This Phase 3, multicenter, parallel-group, placebo-controlled, randomized, double-blind study will be conducted in Australia and/or another southern hemisphere country. Healthy adults ≥65 years of age will be randomized 1:1 to either the coadministration group (RSVpreF + SIIV)/placebo or the sequential-administration group (placebo + SIIV)/RSVpreF. This study design intends to use a single lot of NIP SIIV that is specifically indicated for use in adults ≥65 years of age. There are 3 scheduled study visits each 1 month apart. To assess immunogenicity, 30 mL blood will be collected prior to vaccination at Visit 1 and Visit 2, and at Visit 3. Local reactions (redness, swelling, and pain at the injection site) occurring at the RSVpreF or placebo injection site (left deltoid) and systemic events (fever, headache, fatigue, nausea, vomiting, diarrhea, muscle pain, and joint pain) occurring within 7 days after each vaccination visit (Visit 1 and Visit 2) will be prompted for and collected daily by the participant in an e-diary device or smartphone app. SIIV injection site reactions will not be routinely collected in the e-diary. AEs and SAEs will be collected from the signing of informed consent through Visit 3.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

1,471

Conditions

Respiratory Syncytial Virus

Interventions

RSVpreF VaccineBIOLOGICAL

RSV Vaccine

PlaceboOTHER

Placebo

Seasonal Inactivated Influenza VaccineBIOLOGICAL

SIIV

Eligibility

Sex: ALLMin age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Male and female participants ≥65 years of age at the time of consent. 2. Participants who are willing and able to comply with scheduled visits, laboratory tests, lifestyle considerations, and other study procedures, including daily completion of the e diary for 7 days after each study vaccination. 3. Healthy participants who are determined by medical history, physical examination and clinical judgment of the investigator to be eligible for inclusion in the study. 4. Capable of giving signed informed consent Exclusion Criteria: 1. Bleeding diathesis or condition associated with prolonged bleeding time that may contraindicate IM injection. 2. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention or any related vaccine. 3. Allergy to egg proteins (egg or egg products) or chicken proteins. 4. History of Guillain-Barré syndrome. 5. 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. 6. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination. 7. 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. 8. Previous vaccination with any licensed or investigational RSV vaccine at any time prior to enrollment, or planned receipt throughout the study of nonstudy RSV vaccine. 9. Previous vaccination with any influenza vaccine within 6 months before study intervention administration, or planned receipt of any nonstudy licensed or investigational influenza vaccine during study participation. 10. Receipt of any blood/plasma products or immunoglobulin, from 60 days before study intervention administration, or planned receipt throughout the study. 11. Individuals who receive chronic treatment with immunosuppressive therapy, including cytotoxic agents, monoclonal antibodies, systemic corticosteroids, or radiotherapy, eg, for cancer or an autoimmune disease, from 60 days before study intervention administration or planned receipt throughout the study. If systemic corticosteroids (\<20 mg/day of prednisone or equivalent) have been administered short term (\<14 days) for treatment of an acute illness, participants should not be enrolled in the study until corticosteroid therapy has been discontinued for at least 28 days before study intervention administration. Inhaled/nebulized, intra articular, intrabursal, or topical (skin or eyes) corticosteroid use is permitted. 12. Current alcohol abuse or illicit drug use. 13. Current use of any prohibited concomitant medication(s) or those unwilling/unable to use a permitted concomitant medication(s) 14. Participation in other studies involving investigational product(s) within 28 days prior to consent and/or during study participation 15. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members

Locations (33)

Outcomes

Primary Outcomes

Percentage of Participants Reporting Local Reactions Within 7 Days After Vaccination With RSVpreF or Placebo

Local reactions were collected at the RSVpreF or placebo injection site after Vaccination 1 and Vaccination 2 and were recorded by participants using electronic diary (e-diary). Local reactions included redness, swelling and pain at injection site. Redness and swelling were measured and recorded in measuring device units where, 1 measuring device unit =0.5 centimeter (cm) and were graded as mild (greater than \[\>\] 2.0 to 5.0 cm), moderate (\>5.0 to 10.0 cm), and severe (\>10.0 cm). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), and severe (prevented daily activity). Percentage of participants reporting local reactions at injection site in Coadministration Group, and Sequential-Administration Group and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented in this outcome measure (OM). Safety population=all enrolled participants who received study intervention (RSVpreF, placebo).

Time frame: Within 7 days after Vaccination 1 or Vaccination 2

Percentage of Participants Reporting Systemic Events Within 7 Days After Vaccination With RSVpreF or Placebo

Systemic events included fever, fatigue, headache, nausea, vomiting, diarrhea, muscle pain and joint pain and were recorded by participants using an e-diary. Fever was defined as an oral temperature \>=38.0 degree Celsius (deg C) and categorized as \>=38.0 to 38.4 deg C (mild), \>38.4 to 38.9 deg C (moderate), \>38.9 to 40.0 deg C (severe) and \>40.0 deg C (grade 4). Fatigue, headache, nausea, muscle pain and joint pain were graded as mild (did not interfere with activity), moderate (some interference with activity) and severe (prevented daily routine activity). Vomiting was graded mild: 1 to 2 times in 24 hours (h), moderate: \>2 times in 24h, and severe: required intravenous hydration. Diarrhea was graded mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h and severe: 6 or more loose stools in 24h. Percentage of participants with systemic events within 7 days after each vaccination and the associated 2-sided 95% CI based on the Clopper and Pearson method was presented.

Time frame: Within 7 days after Vaccination 1 or Vaccination 2

Percentage of Participants Reporting Adverse Events (AEs) Within 1 Month After Vaccination 1

Data from ClinicalTrials.gov

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Secondary Outcomes

Geometric Mean of the Neutralizing Titers for RSV A and RSV B Before Vaccination and at 1 Month and 2 Months After Vaccination With RSVpreF

GMT of neutralizing titers of RSV A and RSV B before vaccination, at 1 month and 2 months after vaccination was reported in this outcome measure. Assay results below the LLOQ were set to 0.5\*LLOQ. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). For Sequential-Administration Group, the time point for 2 months after vaccination was not reported since the participants received RSVpreF at Vaccination 2 and were followed up for 1 month after Vaccination 2.

Time frame: Coadministration Group: before RSVpreF vaccination, and 1 and 2 months after RSVpreF vaccination; Sequential-Administration Group: before RSVpreF vaccination (most recent serology results before RSVpreF) and 1 month after RSVpreF vaccination

Geometric Mean Fold Rise (GMFR) of the NTs for RSV A and RSV B Before Vaccination and at 1 Month and 2 Months After Vaccination With RSVpreF

GMFR of neutralizing titers of RSV A and RSV B before vaccination and at 1 month and 2 months after vaccination was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the Student's t distribution).

Time frame: Coadministration Group: before RSVpreF vaccination, and 1 and 2 months after vaccination; Sequential-Administration Group: before RSVpreF vaccination (most recent serology results before RSVpreF) and 1 month after vaccination

HAI Geometric Mean Titer (GMT) Before Vaccination and 1 Month After Vaccination With SIIV

HAI GMT before vaccination and 1 month after vaccination with SIIV was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).

Time frame: Before SIIV vaccination, and 1 month after vaccination

GMFR of Strain-Specific HAI Titers Before Vaccination and 1 Month After Vaccination With SIIV

GMFR of strain-specific HAI titers before vaccination and 1 month after vaccination with SIIV was reported in this outcome measure. GMFRs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of fold rises (later time point over earlier time point) and the corresponding CIs (based on Student's t distribution).

Time frame: Before SIIV vaccination, and 1 month after vaccination