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

• Sponsor: BioNTech SE (Industry)
• Overall Status: Completed
• CT.gov ID: NCT05310084
• Collaborator: Pfizer (Industry)
• Enrollment: 1,134
• Locations: 26
• Arms: 2
• Actual Duration (Months): 5.5
• Patients Per Site: 43.6
• Patients Per Site Per Month: 7.9

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
SARS-CoV-2 Infection; COVID-19	Biological: BNT162b2; Other: Placebo; Biological: Seasonal Inactivated Influenza Vaccine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1134 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: This is an Observer-Blind Study. The vaccines and placebo will be administered by an unblinded third-party site staff member.
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: Apr 20, 2022
• Actual Primary Completion Date: Oct 5, 2022
• Actual Study Completion Date: Oct 5, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Coadministration Group BNT162b2 and SIIV followed by placebo a month later	Biological: BNT162b2; Intramuscular injection; Other: Placebo; Saline intramuscular injection; Biological: Seasonal Inactivated Influenza Vaccine; SIIV intramuscular injection
Experimental: Separate Administration Group Placebo and SIIV followed by BNT162b2 a month later	Biological: BNT162b2; Intramuscular injection; Other: Placebo; Saline intramuscular injection; Biological: Seasonal Inactivated Influenza Vaccine; SIIV intramuscular injection

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Local Reactions Within 7 Days After Vaccination 1 [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.

2. Percentage of Participants With Local Reactions Within 7 Days After Vaccination 2 [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.

3. Percentage of Participants With Systemic Events Within 7 Days After Vaccination 1 [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.

4. Percentage of Participants With Systemic Events Within 7 Days After Vaccination 2 [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.

5. Percentage of Participants With Adverse Events Within 1 Month After Vaccination 1 [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.

6. Percentage of Participants With Adverse Events Within 1 Month After Vaccination 2 [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.

7. Percentage of Participants With Serious Adverse Events Within 1 Month After Vaccination 1 [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.

8. Percentage of Participants With Serious Adverse Events Within 1 Month After Vaccination 2 [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.

9. Geometric Mean Ratio (GMR) Based on Geometric Mean Concentration (GMC) of Full-Length S-binding Immunoglobulin G (IgG) at 1 Month After BNT162b2 Vaccination [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.

10. Geometric Mean Ratio (GMR) Based on Geometric Mean Titer (GMT) of Strain-Specific Hemagglutination Inhibition (HAI) at 1 Month After SIIV Vaccination [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.

Secondary Outcome Measures

1. Geometric Mean Concentration (GMC) of Full-Length S-binding IgG Levels Before Vaccination and 1 Month After BNT162b2 Vaccination [Before BNT162b2 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''.

2. Geometric Mean Fold Rise (GMFR) of Full-Length S-binding IgG Levels From Before Vaccination to 1 Month After BNT162b2 Vaccination [From before BNT162b2 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''.

3. 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]

4. Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Titers From Before Vaccination to 1 Month After BNT162b2 Vaccination [From before BNT162b2 vaccination to 1 month after BNT162b2 vaccination]

   SARS-CoV-2 neutralization assay (reference strain) (for a subset of approximately 200 participants).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Participants 18 through 64 years of age, inclusive, at the time of consent.

2. Are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

3. 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.

4. 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.

5. 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:

1. 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.

2. Allergy to egg proteins (egg or egg products) or chicken proteins.

3. History of Guillain-Barré syndrome.

4. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).

5. A positive SARS-CoV-2 test result (either by NAAT or rapid antigen test) within 28 days of Visit 1 (Day 1).

6. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.

7. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.

8. Women who are pregnant or breastfeeding.

9. 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.

10. 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.

11. Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study.

12. Receipt of any passive antibody therapy specific to COVID-19 from 90 days before study intervention administration or planned receipt throughout the study.

13. Prior receipt of any COVID-19 vaccine other than BNT162b2 or receipt of more than 3 prior doses of BNT162b2.

14. Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.

15. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northern Beaches Clinical Research	Brookvale	New South Wales	Australia	2100
2	Australian Clinical Research Network	Sydney	New South Wales	Australia	NSW 2035
3	Westmead Hospital	Westmead	New South Wales	Australia	2145
4	Paratus Clinical Research Brisbane	Albion	Queensland	Australia	4010
5	AusTrials - Wellers Hill	Wellers Hill	Queensland	Australia	4121
6	Emeritus Research	Camberwell	Victoria	Australia	3124
7	Barwon Health	Geelong	Victoria	Australia	3220
8	New Zealand Clinical Research (Auckland)	Grafton	Auckland	New Zealand	1010
9	Optimal Clinical Trials	Grafton	Auckland	New Zealand	1010
10	Southern Clinical Trials Totara	New Lynn	Auckland	New Zealand	0600
11	Lakeland Clinical Trials Culloden	Papamoa Beach	BAY OF Plenty	New Zealand	3118
12	Pacific Clinical Research Network - Rotorua	Rotorua	BAY OF Plenty	New Zealand	3010
13	P3 Research - Tauranga	Tauranga	BAY OF Plenty	New Zealand	3110
14	New Zealand Clinical Research (Christchurch)	Christchurch	Canterbury	New Zealand	8011
15	Pacific Clinical Research Network - Forte	Christchurch	Canterbury	New Zealand	8013
16	P3 Research - Hawke's Bay	Havelock North	Hawke's BAY	New Zealand	4130
17	P3 Research - Palmerston North	Palmerston North	Manawatu-wanganui	New Zealand	4414
18	Lakeland Clinical Trials Waikato	Hamilton	Waikato	New Zealand	3200
19	Lakeland Clinical Trials Wellington	Ebdentown. Upper Hutt	Wellington	New Zealand	5018
20	P3 Research - Kapiti	Paraparaumu	Wellington	New Zealand	5032
21	Southern Clinical Trials Waitemata Ltd	Auckland		New Zealand	0626
22	Aotearoa Clinical Trials	Auckland		New Zealand	2025
23	Middlemore Clinical Trials	Auckland		New Zealand	2025
24	Southern Clinical Trials Tasman	Nelson		New Zealand	7011
25	Capital, Coast and Hutt Valley District - Wellington Regional Hospital	Wellington		New Zealand	6021
26	P3 Research - Wellington	Wellington		New Zealand	6021

Sponsors and Collaborators

• BioNTech SE
• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

• Study Protocol - Mar 9, 2022
• Statistical Analysis Plan - Oct 20, 2022

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: BioNTech SE
• ClinicalTrials.gov Identifier: NCT05310084
• Other Study ID Numbers: C4591030; NCT06137001
• First Posted: Apr 4, 2022
• Last Update Posted: Nov 24, 2023
• Last Verified: Nov 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by BioNTech SE: COVID-19; Coronavirus; Vaccine; SARS-CoV-2; RNA Vaccine
• Additional relevant MeSH terms: COVID-19

Study Results

Participant Flow

Recruitment Details	A total of 1165 participants were screened, out of which 31 were screen failures and 1134 were randomized into the study.

Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Period Title: Overall Study
STARTED	568	566
Vaccinated	564	564
COMPLETED	560	555
NOT COMPLETED	8	11

Baseline Characteristics

Arm/Group Title	Coadministration Group	Separate Administration Group	Total
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).	Total of all reporting groups
Overall Participants	564	564	1128
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	39.7 (13.20)	39.8 (13.52)	39.7 (13.35)
Sex: Female, Male (Count of Participants)
Female	356 63.1%	361 64%	717 63.6%
Male	208 36.9%	203 36%	411 36.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 0.9%	9 1.6%	14 1.2%
Not Hispanic or Latino	539 95.6%	537 95.2%	1076 95.4%
Unknown or Not Reported	20 3.5%	18 3.2%	38 3.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	73 12.9%	66 11.7%	139 12.3%
Native Hawaiian or Other Pacific Islander	26 4.6%	36 6.4%	62 5.5%
Black or African American	1 0.2%	2 0.4%	3 0.3%
White	446 79.1%	439 77.8%	885 78.5%
More than one race	1 0.2%	10 1.8%	11 1%
Unknown or Not Reported	17 3%	11 2%	28 2.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Local Reactions Within 7 Days After Vaccination 1
Description	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.
Time Frame	Within 7 Days After Vaccination 1

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any of the study intervention. Here, ''Number of participants analyzed'' signifies number of participants evaluable and "Number Analyzed" (n) signifies number of participants evaluable for specified rows for this outcome measure.

Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Measure Participants	564	563
Redness: Any	7.6 1.3%	0.5 0.1%
Redness: Mild	6.2 1.1%	0.5 0.1%
Redness: Moderate	1.2 0.2%	0 0%
Redness: Severe	0.2 0%	0 0%
Redness: Grade 4	0 0%	0 0%
Swelling: Any	9.2 1.6%	1.1 0.2%
Swelling: Mild	6.2 1.1%	0.4 0.1%
Swelling: Moderate	3.0 0.5%	0.7 0.1%
Swelling: Severe	0 0%	0 0%
Swelling: Grade 4	0 0%	0 0%
Pain at the injection site: Any	86.2 15.3%	13.9 2.5%
Pain at the injection site: Mild	66.3 11.8%	13.5 2.4%
Pain at the injection site: Moderate	19.9 3.5%	0.4 0.1%
Pain at the injection site: Severe	0 0%	0 0%
Pain at the injection site: Grade 4	0 0%	0 0%

2. Primary Outcome

Title	Percentage of Participants With Local Reactions Within 7 Days After Vaccination 2
Description	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.
Time Frame	Within 7 Days After Vaccination 2

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any of the study intervention. Here, "Number of participants analyzed" included participants who received Vaccination 2 and signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Measure Participants	557	553
Redness: Any	0.2 0%	4.7 0.8%
Redness: Mild	0.2 0%	4.3 0.8%
Redness: Moderate	0 0%	0.4 0.1%
Redness: Severe	0 0%	0 0%
Redness: Grade 4	0 0%	0 0%
Swelling: Any	0.4 0.1%	8.9 1.6%
Swelling: Mild	0.4 0.1%	5.8 1%
Swelling: Moderate	0 0%	3.1 0.5%
Swelling: Severe	0 0%	0 0%
Swelling: Grade 4	0 0%	0 0%
Pain at the injection site: Any	6.6 1.2%	84.4 15%
Pain at the injection site: Mild	6.3 1.1%	61.7 10.9%
Pain at the injection site: Moderate	0.4 0.1%	22.4 4%
Pain at the injection site: Severe	0 0%	0.4 0.1%
Pain at the injection site: Grade 4	0 0%	0 0%

3. Primary Outcome

Title	Percentage of Participants With Systemic Events Within 7 Days After Vaccination 1
Description	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.
Time Frame	Within 7 Days After Vaccination 1

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any of the study intervention. Here, "Number of participants analyzed" signifies number of participants evaluable and "Number Analyzed" (n) signifies number of participants evaluable for specified rows for this outcome measure.

Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Measure Participants	564	563
Fever: >=38.0 deg C	2.0 0.4%	1.1 0.2%
Fever: >=38.0 deg C to 38.4 deg C	1.2 0.2%	0.4 0.1%
Fever: >38.4 deg C to 38.9 deg C	0.4 0.1%	0.4 0.1%
Fever: >38.9 deg C to 40.0 deg C	0.4 0.1%	0.4 0.1%
Fever: >40.0 deg C	0.0 0%	0.0 0%
Fatigue: Any	64.0 11.3%	42.1 7.5%
Fatigue: Mild	31.9 5.7%	24.7 4.4%
Fatigue: Moderate	30.9 5.5%	16.3 2.9%
Fatigue: Severe	1.2 0.2%	1.1 0.2%
Fatigue: Grade 4	0 0%	0 0%
Headache: Any	47.2 8.4%	34.3 6.1%
Headache: Mild	28.2 5%	23.3 4.1%
Headache: Moderate	17.9 3.2%	10.3 1.8%
Headache: Severe	1.1 0.2%	0.7 0.1%
Headache: Grade 4	0 0%	0 0%
Chills: Any	19.9 3.5%	6.2 1.1%
Chills: Mild	12.9 2.3%	4.3 0.8%
Chills: Moderate	6.0 1.1%	1.6 0.3%
Chills: Severe	0.9 0.2%	0.4 0.1%
Chills: Grade 4	0 0%	0 0%
Vomiting: Any	2.7 0.5%	0.9 0.2%
Vomiting: Mild	2.3 0.4%	0.7 0.1%
Vomiting: Moderate	0.4 0.1%	0.2 0%
Vomiting: Severe	0 0%	0 0%
Vomiting: Grade 4	0 0%	0 0%
Diarrhea: Any	11.5 2%	10.1 1.8%
Diarrhea: Mild	9.9 1.8%	8.9 1.6%
Diarrhea: Moderate	1.4 0.2%	1.2 0.2%
Diarrhea: Severe	0.2 0%	0 0%
Diarrhea: Grade 4	0 0%	0 0%
New or worsened muscle pain: Any	27.7 4.9%	11.4 2%
New or worsened muscle pain: Mild	15.8 2.8%	6.2 1.1%
New or worsened muscle pain: Moderate	11.3 2%	5.0 0.9%
New or worsened muscle pain: Severe	0.5 0.1%	0.2 0%
New or worsened muscle pain: Grade 4	0 0%	0 0%
New or worsened joint pain: Any	15.1 2.7%	5.3 0.9%
New or worsened joint pain: Mild	10.3 1.8%	2.7 0.5%
New or worsened joint pain: Moderate	4.8 0.9%	2.7 0.5%
New or worsened joint pain: Severe	0 0%	0 0%
New or worsened joint pain: Grade 4	0 0%	0 0%

4. Primary Outcome

Title	Percentage of Participants With Systemic Events Within 7 Days After Vaccination 2
Description	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.
Time Frame	Within 7 Days After Vaccination 2

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any of the study intervention. Here, "Number of participants analyzed" included participants who received Vaccination 2 and signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Measure Participants	557	553
Fever: >=38.0 deg C	1.1 0.2%	1.6 0.3%
Fever: >=38.0 deg C to 38.4 deg C	0.5 0.1%	1.1 0.2%
Fever: >38.4 deg C to 38.9 deg C	0.5 0.1%	0.5 0.1%
Fever: >38.9 deg C to 40.0 deg C	0 0%	0 0%
Fever: >40.0 deg C	0. 0%	0 0%
Fatigue: Any	21.7 3.8%	50.8 9%
Fatigue: Mild	12.4 2.2%	27.3 4.8%
Fatigue: Moderate	8.6 1.5%	22.1 3.9%
Fatigue: Severe	0.7 0.1%	1.4 0.2%
Fatigue: Grade 4	0 0%	0 0%
Headache: Any	20.8 3.7%	37.8 6.7%
Headache: Mild	13.1 2.3%	25.0 4.4%
Headache: Moderate	7.5 1.3%	12.1 2.1%
Headache: Severe	0.2 0%	0.7 0.1%
Headache: Grade 4	0 0%	0 0%
Chills: Any	3.4 0.6%	13.4 2.4%
Chills: Mild	2.3 0.4%	8.5 1.5%
Chills: Moderate	1.1 0.2%	4.7 0.8%
Chills: Severe	0 0%	0.2 0%
Chills: Grade 4	0 0%	0 0%
Vomiting: Any	1.1 0.2%	2.4 0.4%
Vomiting: Mild	0.7 0.1%	1.8 0.3%
Vomiting: Moderate	0.4 0.1%	0.5 0.1%
Vomiting: Severe	0 0%	0 0%
Vomiting: Grade 4	0 0%	0 0%
Diarrhea: Any	4.5 0.8%	6.5 1.2%
Diarrhea: Mild	3.8 0.7%	5.2 0.9%
Diarrhea: Moderate	0.7 0.1%	0.9 0.2%
Diarrhea: Severe	0 0%	0.4 0.1%
Diarrhea: Grade 4	0 0%	0 0%
New or worsened muscle pain: Any	5.2 0.9%	23.5 4.2%
New or worsened muscle pain: Mild	2.7 0.5%	12.8 2.3%
New or worsened muscle pain: Moderate	2.5 0.4%	10.5 1.9%
New or worsened muscle pain: Severe	0 0%	0.2 0%
New or worsened muscle pain: Grade 4	0 0%	0 0%
New or worsened joint pain: Any	3.4 0.6%	9.8 1.7%
New or worsened joint pain: Mild	2.0 0.4%	5.6 1%
New or worsened joint pain: Moderate	1.4 0.2%	4.2 0.7%
New or worsened joint pain: Severe	0 0%	0 0%
New or worsened joint pain: Grade 4	0 0%	0 0%

5. Primary Outcome

Title	Percentage of Participants With Adverse Events Within 1 Month After Vaccination 1
Description	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.
Time Frame	Within 1 month after Vaccination 1

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any of the study intervention.

Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Measure Participants	564	564
Number (95% Confidence Interval) [Percentage of participants]	31.6 5.6%	30.5 5.4%

6. Primary Outcome

Title	Percentage of Participants With Adverse Events Within 1 Month After Vaccination 2
Description	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.
Time Frame	Within 1 month after Vaccination 2

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any of the study intervention. Here, "Number of participants analyzed" signifies number of participants evaluable for this outcome measure''.

Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Measure Participants	562	557
Number (95% Confidence Interval) [Percentage of participants]	29.0 5.1%	25.1 4.5%

7. Primary Outcome

Title	Percentage of Participants With Serious Adverse Events Within 1 Month After Vaccination 1
Description	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.
Time Frame	Within 1 Month After Vaccination 1

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any of the study intervention.

Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Measure Participants	564	564
Number (95% Confidence Interval) [Percentage of participants]	0.4 0.1%	0.2 0%

8. Primary Outcome

Title	Percentage of Participants With Serious Adverse Events Within 1 Month After Vaccination 2
Description	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.
Time Frame	Within 1 Month After Vaccination 2

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any of the study intervention. Here, "Number of participants analyzed" signifies number of participants evaluable for this outcome measure''.

Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Measure Participants	562	557
Number (95% Confidence Interval) [Percentage of participants]	0.5 0.1%	0.7 0.1%

9. Primary Outcome

Title	Geometric Mean Ratio (GMR) Based on Geometric Mean Concentration (GMC) of Full-Length S-binding Immunoglobulin G (IgG) at 1 Month After BNT162b2 Vaccination
Description	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.
Time Frame	1 Month After BNT162b2 vaccination

Outcome Measure Data

Analysis Population Description

Evaluable BNT162b2 immunogenicity population: Eligible participants who received all vaccinations(Vax) at Visit1(V1) (coadministration group) or all Vax at V1 and V2 (separate administration group) as randomized, had at least 1 valid full-length S-binding IgG result from blood sample collected 28 to 42 days after BNT162b2 vax, had no reported COVID-19/new SARS-CoV-2 infection after V1 through 1 month after BNT162b2 vax, and had no other important protocol deviations as determined by clinician.

Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Measure Participants	499	413
Geometric Mean (95% Confidence Interval) [Units per millilitre (U/mL)]	13767.8	16644.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Coadministration Group, Separate Administration Group
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (coadministration group to separate-administration group) was greater than 0.67.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMR
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.77 to 0.89
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMRs and 95% CIs were calculated by exponentiating LSmeans difference of logarithms of concentrations (coadmin group-separate admin group), corresponding CIs based on analysis of log transformed assay results using a linear regression model.

10. Primary Outcome

Title	Geometric Mean Ratio (GMR) Based on Geometric Mean Titer (GMT) of Strain-Specific Hemagglutination Inhibition (HAI) at 1 Month After SIIV Vaccination
Description	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.
Time Frame	1 Month After SIIV vaccination

Outcome Measure Data

Analysis Population Description

Evaluable SIIV immunogenicity population: participants who received all vaccinations at Visit 1 as randomized, had at least 1 valid and determinate HAI titer result from the blood sample collected 28 to 42 days after SIIV, and had no other important protocol deviations as determined by the clinician. Here, "Number of participants analyzed" signifies number of participants evaluable and "Number Analyzed" (n) signifies number of participants evaluable for specified rows for this outcome measure.

Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Measure Participants	515	484
B/Austria	80.1	89.7
B/Phuket	81.3	81.3
H1N1 A/Victoria	301.7	316.5
H3N2 A/Darwin	226.8	235.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Coadministration Group, Separate Administration Group
	Comments	B/Austria
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority was declared for an influenza strain if the lower bound of the 2-sided 95% CI for the GMR (coadministration group to separate administration group) was greater than 0.67
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMRs and 95% CIs were calculated by exponentiating LSmeans difference of logarithms of titers (coadministration group-separate administration group), corresponding CIs based on analysis of log transformed assay results using a linear regression model

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Coadministration Group, Separate Administration Group
	Comments	B/Phuket
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority was declared for an influenza strain if the lower bound of the 2-sided 95% CI for the GMR (coadministration group to separate administration group) was greater than 0.67.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMR
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMRs and 95% CIs were calculated by exponentiating LSmeans difference of logarithms of titers (coadministration group-separate administration group), corresponding CIs based on analysis of log transformed assay results using a linear regression model

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Coadministration Group, Separate Administration Group
	Comments	H1N1 A/Victoria
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority was declared for an influenza strain if the lower bound of the 2-sided 95% CI for the GMR (coadministration group to separate administration group) was greater than 0.67.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMR
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMRs and 95% CIs were calculated by exponentiating LSmeans difference of logarithms of titers (coadministration group-separate administration group), corresponding CIs based on analysis of log transformed assay results using a linear regression model

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Coadministration Group, Separate Administration Group
	Comments	H3N2 A/Darwin
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority was declared for an influenza strain if the lower bound of the 2-sided 95% CI for the GMR (coadministration group to separate administration group) was greater than 0.67.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMR
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMRs and 95% CIs were calculated by exponentiating LSmeans difference of logarithms of titers (coadministration group-separate administration group), corresponding CIs based on analysis of log transformed assay results using a linear regression model

11. Secondary Outcome

Title	Geometric Mean Concentration (GMC) of Full-Length S-binding IgG Levels Before Vaccination and 1 Month After BNT162b2 Vaccination
Description	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''.
Time Frame	Before BNT162b2 vaccination, and 1 month After BNT162b2 vaccination

Outcome Measure Data

Analysis Population Description

Evaluable BNT162b2 immunogenicity population: Eligible participants who received all vaccinations(Vax) at Visit1(V1) (coadministration group) or all Vax at V1 and V2 (separate administration group) as randomized, had at least 1 valid full-length S-binding IgG result from blood sample collected 28 to 42 days after BNT162b2 vax, had no reported COVID-19/new SARS-CoV-2 infection after V1 through 1 month after BNT162b2 vax, and had no other important protocol deviations as determined by clinician.

Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Measure Participants	499	413
Before BNT162b2 Vaccination	5520.3	5272.3
1 Month After BNT162b2 Vaccination	13806.5	16254.6

12. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) of Full-Length S-binding IgG Levels From Before Vaccination to 1 Month After BNT162b2 Vaccination
Description	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''.
Time Frame	From before BNT162b2 vaccination to 1 month After BNT162b2 vaccination

Outcome Measure Data

Analysis Population Description

Evaluable BNT162b2 immunogenicity population: Eligible participants who received all vaccinations(Vax) at Visit1(V1) (coadministration group) or all Vax at V1 and V2 (separate administration group) as randomized, had at least 1 valid full-length S-binding IgG result from blood sample collected 28 to 42 days after BNT162b2 vax, had no reported COVID-19/new SARS-CoV-2 infection after V1 through 1 month after BNT162b2 vax, and had no other important protocol deviations as determined by clinician.

Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Measure Participants	499	413
Geometric Mean (95% Confidence Interval) [Fold rise]	2.5	3.1

13. Secondary Outcome

Title	Geometric Mean Titer (GMT) of SARS-CoV-2 Neutralizing Titers Before Vaccination and 1 Month After BNT162b2 Vaccination
Time Frame	Before BNT162b2 vaccination, and 1 month after BNT162b2 vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Titers From Before Vaccination to 1 Month After BNT162b2 Vaccination
Description	SARS-CoV-2 neutralization assay (reference strain) (for a subset of approximately 200 participants).
Time Frame	From before BNT162b2 vaccination to 1 month after BNT162b2 vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	AEs and SAEs: From Day 1 (Visit 1) to 1 month after last dose of study vaccine (approximately 2 months after Visit 1 [Day1]); Local reactions (at the BNT162b2/placebo injection site) and systemic events: Within 7 days after each vaccination
Adverse Event Reporting Description	An AE may be categorized as serious in 1 participant and non-serious in another participant, or 1 participant may experience both serious and non-serious AE during the study. Safety population included all participants who received any of the study intervention. AEs included events collected in electronic diary (local and systemic reactions; systematic assessment) and events collected on case report form at each visit (non-systematic assessment).
Arm/Group Title	Coadministration Group (Visit 1)		Coadministration Group (Visit 2)		Separate Administration Group (Visit 1)		Separate Administration Group (Visit 2)
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).		Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).		Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).		Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
All Cause Mortality
	Coadministration Group (Visit 1)		Coadministration Group (Visit 2)		Separate Administration Group (Visit 1)		Separate Administration Group (Visit 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/564 (0%)		0/562 (0%)		0/564 (0%)		0/557 (0%)
Serious Adverse Events
	Coadministration Group (Visit 1)		Coadministration Group (Visit 2)		Separate Administration Group (Visit 1)		Separate Administration Group (Visit 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/564 (0.4%)		3/562 (0.5%)		1/564 (0.2%)		4/557 (0.7%)
Cardiac disorders
Atrial fibrillation	0/564 (0%)		0/562 (0%)		0/564 (0%)		1/557 (0.2%)
Gastrointestinal disorders
Intestinal perforation	0/564 (0%)		1/562 (0.2%)		0/564 (0%)		0/557 (0%)
Infections and infestations
Abscess limb	0/564 (0%)		0/562 (0%)		1/564 (0.2%)		0/557 (0%)
Wound infection	1/564 (0.2%)		0/562 (0%)		0/564 (0%)		0/557 (0%)
Injury, poisoning and procedural complications
Concussion	0/564 (0%)		0/562 (0%)		0/564 (0%)		1/557 (0.2%)
Ligament sprain	0/564 (0%)		0/562 (0%)		0/564 (0%)		1/557 (0.2%)
Pneumocephalus	0/564 (0%)		0/562 (0%)		0/564 (0%)		1/557 (0.2%)
Skull fracture	0/564 (0%)		0/562 (0%)		0/564 (0%)		1/557 (0.2%)
Musculoskeletal and connective tissue disorders
Costochondritis	0/564 (0%)		1/562 (0.2%)		0/564 (0%)		0/557 (0%)
Musculoskeletal chest pain	1/564 (0.2%)		0/562 (0%)		0/564 (0%)		1/557 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma stage II	0/564 (0%)		1/562 (0.2%)		0/564 (0%)		0/557 (0%)
Other (Not Including Serious) Adverse Events
	Coadministration Group (Visit 1)		Coadministration Group (Visit 2)		Separate Administration Group (Visit 1)		Separate Administration Group (Visit 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	532/564 (94.3%)		261/562 (46.4%)		364/564 (64.5%)		502/557 (90.1%)
Gastrointestinal disorders
Diarrhoea	65/564 (11.5%)		25/562 (4.4%)		57/564 (10.1%)		36/557 (6.5%)
Vomiting	15/564 (2.7%)		6/562 (1.1%)		5/564 (0.9%)		13/557 (2.3%)
General disorders
Chills	112/564 (19.9%)		19/562 (3.4%)		35/564 (6.2%)		74/557 (13.3%)
Fatigue	361/564 (64%)		121/562 (21.5%)		237/564 (42%)		281/557 (50.4%)
Influenza like illness	9/564 (1.6%)		9/562 (1.6%)		12/564 (2.1%)		7/557 (1.3%)
Injection site erythema	43/564 (7.6%)		1/562 (0.2%)		3/564 (0.5%)		26/557 (4.7%)
Injection site pain	486/564 (86.2%)		37/562 (6.6%)		78/564 (13.8%)		467/557 (83.8%)
Injection site pain	16/564 (2.8%)		1/562 (0.2%)		14/564 (2.5%)		1/557 (0.2%)
Injection site swelling	52/564 (9.2%)		2/562 (0.4%)		6/564 (1.1%)		49/557 (8.8%)
Pyrexia	11/564 (2%)		6/562 (1.1%)		6/564 (1.1%)		9/557 (1.6%)
Infections and infestations
COVID-19	46/564 (8.2%)		63/562 (11.2%)		56/564 (9.9%)		48/557 (8.6%)
Gastroenteritis	8/564 (1.4%)		6/562 (1.1%)		7/564 (1.2%)		5/557 (0.9%)
Upper respiratory tract infection	27/564 (4.8%)		31/562 (5.5%)		24/564 (4.3%)		22/557 (3.9%)
Viral upper respiratory tract infection	4/564 (0.7%)		6/562 (1.1%)		6/564 (1.1%)		7/557 (1.3%)
Nervous system disorders
Headache	266/564 (47.2%)		116/562 (20.6%)		193/564 (34.2%)		209/557 (37.5%)

Limitations/Caveats

The evolving nature of the pandemic has required serology work to be focused on newly emerging strains as a matter of urgent priority, which has delayed serology work on earlier trials. Hence data is not yet available for all serology outcome measures.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.