Safety and Immunogenicity of BNT162b2 Coadministered With SIIV in Adults 18 Through 64 Years of Age

Study Overview
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Brief Summary
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This study will assess the safety and immunogenicity of a fourth dose (booster) of BNT162b2 when coadministered with SIIV compared to separate administration of the vaccines when given 1 month apart (SIIV followed by BNT162b2), in participants who have received 3 prior doses of 30 µg BNT162b2, with the third dose being at least 90 days before Visit 1 (Day 1). Healthy adults 18 through 64 years of age will be randomized 1:1 to either the co-administration group, or the separate administration group The duration of the study for each participant will be approximately 2 months There are 3 scheduled study visits each about 1 month apart The study will be conducted in New Zealand and Australia.

Official Title
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A PHASE 3, RANDOMIZED, OBSERVER-BLIND TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF BNT162b2 WHEN COADMINISTERED WITH SEASONAL INACTIVATED INFLUENZA VACCINE (SIIV) IN ADULTS 18 THROUGH 64 YEARS OF AGE

Conditions
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SARS-CoV-2 Infection, COVID-19

Intervention / Treatment
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* Biological: BNT162b2
* Other: Placebo
* Biological: Seasonal Inactivated Influenza Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants 18 through 64 years of age, inclusive, at the time of consent. Are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. Adults determined by clinical assessment, including medical history and clinical judgment, to be eligible for the study, including adults with preexisting stable disease, defined as disease not requiring significant change in therapy in the previous 6 weeks or hospitalization for worsening disease within 12 weeks before receipt of study intervention. Have received 3 prior doses of 30 µg BNT162b2, with the third dose being at least 90 days before Visit 1 (Day 1). Documented confirmation of prior BNT162b2 receipt must be obtained prior to randomization. Capable of giving personal signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol. Exclusion Criteria: 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. Allergy to egg proteins (egg or egg products) or chicken proteins. History of Guillain-Barré syndrome. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s). A positive SARS-CoV-2 test result (either by NAAT or rapid antigen test) within 28 days of Visit 1 (Day 1). Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection. Women who are pregnant or breastfeeding. Vaccination with any influenza vaccine <6 months before study intervention administration, or planned receipt of any licensed or investigational nonstudy influenza vaccine during study participation. Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids are administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent), eg, for COPD, or planned receipt throughout the study. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted. Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study. Receipt of any passive antibody therapy specific to COVID-19 from 90 days before study intervention administration or planned receipt throughout the study. Prior receipt of any COVID-19 vaccine other than BNT162b2 or receipt of more than 3 prior doses of BNT162b2. Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation. Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Coadministration Group<br>BNT162b2 and SIIV followed by placebo a month later | Biological: BNT162b2<br>* Intramuscular injection<br>Other: Placebo<br>* Saline intramuscular injection<br>Biological: Seasonal Inactivated Influenza Vaccine<br>* SIIV intramuscular injection<br>|
| Experimental: Separate Administration Group<br>Placebo and SIIV followed by BNT162b2 a month later | Biological: BNT162b2<br>* Intramuscular injection<br>Other: Placebo<br>* Saline intramuscular injection<br>Biological: Seasonal Inactivated Influenza Vaccine<br>* SIIV intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Local Reactions Within 7 Days After Vaccination 1 | Local reactions included redness, swelling, and pain at the injection site occurring at the BNT162b2 or placebo injection site. Local reactions were recorded by participants in an electronic diary (e-diary). Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm) and graded as mild: greater than (>) 2.0 to 5.0 cm, moderate: >5.0 to 10.0 cm, severe: >10.0 cm, and potentially life threatening (Grade 4): necrosis or exfoliative dermatitis. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity, and potentially life threatening (Grade 4): emergency room visit or hospitalization for severe pain. Exact 2-sided confidence interval (CI), based on the Clopper and Pearson method was used. | Within 7 Days After Vaccination 1 | 
| Percentage of Participants With Local Reactions Within 7 Days After Vaccination 2 | Local reactions included redness, swelling, and pain at the injection site occurring at the BNT162b2 or placebo injection site. Local reactions were recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm and graded as mild: greater than >2.0 to 5.0 cm, moderate: >5.0 to 10.0 cm, severe: >10.0 cm, and potentially life threatening (Grade 4): necrosis or exfoliative dermatitis. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity, and potentially life threatening (Grade 4): emergency room visit or hospitalization for severe pain. Exact 2-sided CI, based on the Clopper and Pearson method was used. | Within 7 Days After Vaccination 2 | 
| Percentage of Participants With Systemic Events Within 7 Days After Vaccination 1 | Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain recorded by participants in an e-diary. Fever was defined as temperature: >=38.0 degrees (deg) Celsius (C), and categorized as: >=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C, and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, and new or worsened joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity, and severe: prevented daily routine activity. Vomiting graded as mild: 1 to 2 times in 24 hours(h), moderate: >2 times in 24h, severe: required intravenous hydration, and grade 4: emergency room (ER) visit or hospitalization for hypotensive shock. Diarrhea graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h, severe: 6 or more loose stools in 24h, and grade 4: ER visit or hospitalization for severe diarrhea. | Within 7 Days After Vaccination 1 | 
| Percentage of Participants With Systemic Events Within 7 Days After Vaccination 2 | Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain recorded by participants in an e-diary. Fever was defined as temperature: >=38.0 deg C, and categorized as: >=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C, and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, and new or worsened joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity, and severe: prevented daily routine activity. Vomiting graded as mild: 1 to 2 times in 24h, moderate: >2 times in 24h, severe: required intravenous hydration, and grade 4: ER visit or hospitalization for hypotensive shock. Diarrhea graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h, severe: 6 or more loose stools in 24h, and grade 4: ER visit or hospitalization for severe diarrhea. Exact 2-sided CI, based on Clopper and Pearson method used. | Within 7 Days After Vaccination 2 | 
| Percentage of Participants With Adverse Events Within 1 Month After Vaccination 1 | An AE was defined as 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. Exact 2-sided CI was calculated using the Clopper and Pearson method. | Within 1 month after Vaccination 1 | 
| Percentage of Participants With Adverse Events Within 1 Month After Vaccination 2 | An AE was defined as 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. Exact 2-sided CI was calculated using the Clopper and Pearson method. | Within 1 month after Vaccination 2 | 
| Percentage of Participants With Serious Adverse Events Within 1 Month After Vaccination 1 | An AE was defined as 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. Exact 2-sided CI was calculated using the Clopper and Pearson method. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; or that was considered to be an important medical event. | Within 1 Month After Vaccination 1 | 
| Percentage of Participants With Serious Adverse Events Within 1 Month After Vaccination 2 | An AE was defined as 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. Exact 2-sided CI was calculated using the Clopper and Pearson method. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; or that was considered to be an important medical event. | Within 1 Month After Vaccination 2 | 
| Geometric Mean Ratio (GMR) Based on Geometric Mean Concentration (GMC) of Full-Length S-binding Immunoglobulin G (IgG) at 1 Month After BNT162b2 Vaccination | GMCs of full-length S-binding IgG level for the coadministration group and separate administration group were reported in this outcome measure in descriptive data section. GMC and the 2-sided 95% CI were calculated by exponentiating the LSMeans of the concentrations and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of vaccine group, age group, and the corresponding baseline assay results (log scale). Assay results below the LLOQ were set to 0.5*LLOQ. Geometric mean ratio (GMR) was reported in the statistical analysis section and was calculated as ratio of GMCs in the coadministration group to the separate administration group. Here, Number of participants analyzed signifies number of participants evaluable for this outcome measure. | 1 Month After BNT162b2 vaccination | 
| Geometric Mean Ratio (GMR) Based on Geometric Mean Titer (GMT) of Strain-Specific Hemagglutination Inhibition (HAI) at 1 Month After SIIV Vaccination | GMTs of strain-specific HAI titers for the coadministration group and separate administration group were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the LSMeans of the titers and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of vaccine group, age group, and the corresponding baseline assay results (log scale). Assay results below the LLOQ were set to 0.5*LLOQ, and results above the ULOQ were set to ULOQ+1. Geometric mean ratio (GMR) was reported in the statistical analysis section and was calculated as ratio of GMT in the coadministration group to the separate administration group. Here, Number of participants analyzed signifies number of participants evaluable for this outcome measure. | 1 Month After SIIV vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Concentration (GMC) of Full-Length S-binding IgG Levels Before Vaccination and 1 Month After BNT162b2 Vaccination | GMCs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student's t-distribution). Assay results below the lower limit of quantitation (LLOQ) were set to 0.5*LLOQ. Here, Number of participants analyzed signifies number of participants evaluable for this outcome measure''. | Before BNT162b2 vaccination, and 1 month After BNT162b2 vaccination | 
| Geometric Mean Fold Rise (GMFR) of Full-Length S-binding IgG Levels From Before Vaccination to 1 Month After BNT162b2 Vaccination | GMFR was defined as ratio of the geometric mean concentration of IgG at 1 month after BNT162b2 vaccination to the geometric mean concentration of IgG before BNT162b2 vaccination. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student's t-distribution). Assay results below the LLOQ were set to 0.5*LLOQ. Here, Number of participants analyzed signifies number of participants evaluable for this outcome measure''. | From before BNT162b2 vaccination to 1 month After BNT162b2 vaccination | 
| Geometric Mean Titer (GMT) of SARS-CoV-2 Neutralizing Titers Before Vaccination and 1 Month After BNT162b2 Vaccination |  | Before BNT162b2 vaccination, and 1 month after BNT162b2 vaccination | 
| Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Titers From Before Vaccination to 1 Month After BNT162b2 Vaccination | SARS-CoV-2 neutralization assay (reference strain) (for a subset of approximately 200 participants). | From before BNT162b2 vaccination to 1 month after BNT162b2 vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronavirus, COVID-19, Vaccine, SARS-CoV-2, RNA Vaccine