Clinical trial NCT05596734: A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Combined Modified RNA Vaccine Candidates Against COVID-19 and Influenza
Official title: A PHASE 1/2 STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF COMBINED MODIFIED RNA VACCINE CANDIDATES AGAINST COVID-19 AND INFLUENZA IN HEALTHY INDIVIDUALS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Influenza, Human
COVID-19
Keywords: SARS-Cov-2
COVID-19
Influenza
Grippe
Flu
Vaccine
RNA vaccine
Lead sponsor: BioNTech SE
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2022-10-27
Enrollment: 1019
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Substudy A: This is a Phase 1 randomized, open-label study to describe the safety and immunogenicity of up to 3 dose- level combinations of modRNA quadrivalent influenza vaccine (qIRV (22/23)) and bivalent BNT162b2 (original/Omi BA.4/BA.5). Participants will receive either:

* qIRV (22/23)/bivalent BNT162b2 (original/Omi BA.4/BA.5), at 1 of the 3 dose-level combinations
* qIRV (22/23) at dose level 1,
* qIRV (22/23) at dose level 2, or
* bivalent BNT162b2 (original/Omi BA.4/BA.5) at dose level 1 administered concurrently in the opposite arm to commercially licensed quadrivalent influenza vaccine (QIV).

Substudy B: This Phase 1/2 study will describe the safety, tolerability, and immunogenicity of quadrivalent influenza vaccine (qIRV)/bivalent BNT162b2 (original/Omi BA.4/BA.5), trivalent influenza vaccine (tIRV)/bivalent BNT162b2 (original/Omi BA.4/BA.5), and bivalent influenza vaccine (bIRV)/bivalent BNT162b2 (original/Omi BA.4/BA.5) when given concurrently with licensed quadrivalent influenza vaccine (QIV).


Eligibility criteria: SSA: Inclusion Criteria:

* Male or female participants 18 years of age and older
* Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures.
* Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
* Capable of giving signed informed consent as described in the protocol.
* For participants 18 through 64 years of age: participants who have received 3 prior doses of 30 µg BNT162b2, with the last dose being 150 to 365 days before Visit 1 (Day 1).
* For participants 65 years of age and older: participants who have received 4 or 5 prior doses of a modRNA SARS-CoV-2 vaccine, with the last dose being a bivalent vaccine, 120 days to 365 days before Visit 1 (Day 1).
* For Participants 65 years of age and older: receipt of licensed influenza vaccination for the 2022-2023 northern hemisphere season 120 days or more before study intervention administration.

SSA: Exclusion Criteria:

* History of severe adverse reaction associated with any vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
* Immunocompromised individuals with known or suspected immunodeficiency.
* Bleeding diathesis or condition associated with prolonged bleeding.
* Women who are pregnant or breastfeeding.
* Allergy to egg proteins (egg or egg products) or chicken proteins.
* Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
* Receipt of chronic systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids), or radiotherapy, within 60 days before enrollment through conclusion of the study.
* Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or planned receipt throughout the study.
* For participants 18 through 64 years of age: vaccination with any investigational or licensed influenza vaccine within 6 months (175 days) before study intervention administration.
* Participation in other studies involving a study intervention within 28 days before randomization. Anticipated participation in other studies within 28 days after receipt of study intervention in this study.
* 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.
* Participation in strenuous or endurance exercise through Visit 3 of the study.
* Prior history of heart disease.
* Any abnormal screening troponin I laboratory value.
* Screening 12-lead ECG that, as judged by the investigator, is consistent with probable or possible myocarditis or pericarditis, or demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.

SSB: Inclusion Criteria

* Male or female participants 18 years of age and older
* Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures.
* Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
* Capable of giving signed informed consent as described in the protocol.
* Participants who have received at least 3 prior US-authorized mRNA COVID-19 vaccines, with the last dose being an updated (bivalent) vaccine given at least 150 days before Day 1.

SSB: Exclusion Criteria

* 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.
* History of severe adverse reaction associated with any vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
* 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
* Receipt of chronic systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids), or radiotherapy, within 60 days before enrollment through conclusion of the study.
* Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or planned receipt throughout the study.
* Vaccination with any investigational or licensed influenza vaccine within 6 months (175 days) before study intervention administration, or ongoing receipt of chronic antiviral therapy with activity against influenza
* Participation in other studies involving administration of a study intervention within 28 days prior to, and/or during, participation in this study.
* 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.
* Initial enrollment only: Participation in strenuous or endurance exercise through Visit 3 (initial enrollment phase).
* Initial enrollment only: Prior history of heart disease of concern
* Initial enrollment only: Screening 12-lead ECG that, as judged by the investigator, is consistent with probable or possible myocarditis or pericarditis, or demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.

Primary outcomes:
measure: SSA: Percentage of participants reporting local reactions
timeFrame: For 7 days after vaccination
measure: SSA: Percentage of participants reporting systemic events
timeFrame: For 7 days after vaccination
measure: SSA: Percentage of participants reporting adverse events
timeFrame: For 4 weeks after vaccination
measure: SSA: Percentage of participants reporting serious adverse events
timeFrame: For 6 months after vaccination
measure: SSA: Percentage of participants with abnormal troponin I laboratory values
timeFrame: 2 days after vaccination
measure: SSA: Percentage of participants with abnormal troponin I laboratory values
timeFrame: 1 week after vaccination
measure: SSA: Percentage of participants with new electrocardiogram (ECG) abnormalities
timeFrame: 2 days after vaccination
measure: SSA: Percentage of participants with new ECG abnormalities
timeFrame: 1 week after vaccination
measure: SSB Initial Enrollment: Percentage of participants with abnormal troponin I laboratory values
timeFrame: 2 days after vaccination
measure: SSB Initial Enrollment: Percentage of participants with abnormal troponin I laboratory values
timeFrame: 1 week after vaccination
measure: SSB Initial Enrollment: Percentage of participants with new electrocardiogram (ECG) abnormalities
timeFrame: 2 days after vaccination
measure: SSB Initial Enrollment: Percentage of participants with new electrocardiogram (ECG) abnormalities
timeFrame: 1 week after vaccination
measure: SSB: Percentage of participants reporting local reactions
timeFrame: For 7 days after vaccination
measure: SSB: Percentage of participants reporting systemic events
timeFrame: For 7 days after vaccination
measure: SSB: Percentage of participants reporting adverse events
timeFrame: For 4 weeks after vaccination
measure: SSB: Percentage of participants reporting serious adverse events
timeFrame: For 6 months after vaccination
Secondary outcomes:
measure: SSA: Geometric Mean Titers (GMTs) of hemagglutination inhibition (HAI) titers
timeFrame: At baseline, and 1-, 4-, and 8-weeks after vaccination
measure: SSA: Geometric Mean Fold Rise (GMFRs) of HAI titers
timeFrame: At baseline, and 1-, 4-, and 8-weeks after vaccination
measure: SSA: Proportion of participants achieving HAI seroconversion for each strain
timeFrame: At 1-, 4-, and 8-weeks after vaccination
measure: SSA: Percentage of participants with HAI titers ≥ 1:40 for each strain
timeFrame: Before vaccination and at 1-, 4-, 8-weeks after vaccination
measure: SSA: Percentage of participants achieving HAI seroconversion for all strains
timeFrame: At 1-, 4-, 8-weeks after vaccination
measure: SSA: Percentage of participants with HAI ≥1:40 for all strains
timeFrame: At 1-, 4-, 8-weeks after vaccination
measure: SSA: GMTs of SARS-CoV-2 Omicron (BA.4/BA.5)-neutralizing titers and SARS-CoV-2 reference-strain-neutralizing titers
timeFrame: At 1-, 4-, and 8 weeks after vaccination
measure: SSA: GMFRs of SARS-CoV-2 Omicron (BA.4/BA.5)-neutralizing titers and SARS-CoV-2 reference-strain-neutralizing titers
timeFrame: At 1-, 4-, and 8 weeks after vaccination
measure: SSA: Percentage of participants with seroresponse based on SARS-CoV-2 Omicron (BA.4/BA.5)-neutralizing titers and SARS-CoV-2 reference-strain-neutralizing titers
timeFrame: At 1-, 4-, and 8 weeks after vaccination.
measure: SSB: Geometric Mean Titers (GMTs) of hemagglutination inhibition (HAI) titers
timeFrame: Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination
measure: SSB: Geometric Mean Fold Rise (GMFRs) of HAI titers
timeFrame: Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination
measure: SSB: Proportion of participants achieving HAI seroconversion for each strain
timeFrame: Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination
measure: SSB: Percentage of participants with HAI titers ≥ 1:40 for each strain
timeFrame: Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination
measure: SSB: Percentage of participants achieving HAI seroconversion for all strains
timeFrame: Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination
measure: SSB: Percentage of participants with HAI ≥1:40 for all strains
timeFrame: Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination
measure: SSB: GMTs of SARS-CoV-2 Omicron (BA.4/BA.5)-neutralizing titers and SARS-CoV-2 reference-strain-neutralizing titers
timeFrame: Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination
measure: SSB: GMFRs of SARS-CoV-2 Omicron (BA.4/BA.5)-neutralizing titers and SARS-CoV-2 reference-strain-neutralizing titers
timeFrame: Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination
measure: SSB: Percentage of participants with seroresponse based on SARS-CoV-2 Omicron (BA.4/BA.5)-neutralizing titers and SARS-CoV-2 reference-strain-neutralizing titers
timeFrame: Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination
Other outcomes:
Locations:
city: Athens
country: United States
facility: North Alabama Research Center
state: Alabama
city: Athens
country: United States
facility: The Heart Center
state: Alabama
city: Phoenix
country: United States
facility: HOPE Research Institute
state: Arizona
city: Phoenix
country: United States
facility: The Pain Center of Arizona
state: Arizona
city: Lake Forest
country: United States
facility: Orange County Research Center
state: California
city: Orange
country: United States
facility: Orange County Heart Institute
state: California
city: San Diego
country: United States
facility: California Research Foundation
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Fort Lauderdale
country: United States
facility: Proactive Clinical Research,LLC
state: Florida
city: Greenacres City
country: United States
facility: Finlay Medical Research
state: Florida
city: Hialeah
country: United States
facility: Indago Research & Health Center, Inc
state: Florida
city: Hollywood
country: United States
facility: Research Centers of America ( Hollywood )
state: Florida
city: Miami Lakes
country: United States
facility: Palm Springs Community Health Center
state: Florida
city: Miami Lakes
country: United States
facility: Panax Clinical Research
state: Florida
city: Miami Lakes
country: United States
facility: Palm Springs Community Health Center
state: Florida
city: Miami
country: United States
facility: Angels Clinical Research Institute
state: Florida
city: Miami
country: United States
facility: Miami Clinical Research
state: Florida
city: Miami
country: United States
facility: Gerardo Polanco, MD
state: Florida
city: Miami
country: United States
facility: Research Institute of South Florida
state: Florida
city: Miami
country: United States
facility: Entrust Clinical Research
state: Florida
city: Miami
country: United States
facility: Jackson Medical Group Cardiac Care
state: Florida
city: Miami
country: United States
facility: Miami Dade Medical Research Institute, LLC
state: Florida
city: Palmetto Bay
country: United States
facility: Innovation Medical Research Center
state: Florida
city: Pembroke Pines
country: United States
facility: DBC Research USA
state: Florida
city: Port Orange
country: United States
facility: United Medical Research
state: Florida
city: Savannah
country: United States
facility: Velocity Clinical Research, Savannah
state: Georgia
city: Savannah
country: United States
facility: Savannah Medical Group
state: Georgia
city: Stockbridge
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Chicago
country: United States
facility: Great Lakes Clinical Trials - Ravenswood
state: Illinois
city: Elmhurst
country: United States
facility: Retina Associates
state: Illinois
city: Oak Brook
country: United States
facility: Affinity Health
state: Illinois
city: Oak Brook
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Illinois
city: Wichita
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Kansas
city: Silver Spring
country: United States
facility: Jadestone Clinical Research
state: Maryland
city: Farmington Hills
country: United States
facility: Michigan Center of Medical Research (MICHMER)
state: Michigan
city: Bridgeton
country: United States
facility: Pradeep Chandra, DO, FACC
state: Missouri
city: Chesterfield
country: United States
facility: Clinical Research Professionals
state: Missouri
city: Saint Louis
country: United States
facility: Sundance Clinical Research
state: Missouri
city: Lincoln
country: United States
facility: Pioneer Heart Institute
state: Nebraska
city: Omaha
country: United States
facility: Quality Clinical Research
state: Nebraska
city: Omaha
country: United States
facility: Velocity Clinical Research, Omaha
state: Nebraska
city: Portsmouth
country: United States
facility: ActivMed Practices & Research, LLC.
state: New Hampshire
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Institute for Global Health
state: New York
city: Monroe
country: United States
facility: Monroe Biomedical Research
state: North Carolina
city: Raleigh
country: United States
facility: M3 Wake Research, Inc.
state: North Carolina
city: Cincinnati
country: United States
facility: CTI Clinical Research Center
state: Ohio
city: Columbus
country: United States
facility: Centricity Research Columbus Ohio Multispecialty
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: East Greenwich
country: United States
facility: Velocity Clinical Research, Providence
state: Rhode Island
city: Little River
country: United States
facility: Main Street Physician's Care
state: South Carolina
city: Little River
country: United States
facility: McLeod Cardiology Associates - Little River
state: South Carolina
city: Knoxville
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Tennessee
city: Knoxville
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Tennessee
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: Prolato Clinical Research Center
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research
state: Texas
city: Charlottesville
country: United States
facility: Charlottesville Medical Research
state: Virginia
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: