A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Combined Modified RNA Vaccine Candidates Against COVID-19 and Influenza

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05596734
• Other study ID #: C5261001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 28, 2022
• Est. completion date: December 28, 2023

Study information

• Verified date: June 2024
• Source: BioNTech SE
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1019
• Est. completion date: December 28, 2023
• Est. primary completion date: December 28, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Influenza, Human

Intervention

Biological:
• bivalent BNT162b2 (original/Omi BA.4/BA.5)
Intramuscular injection
• qIRV (22/23)
Intramuscular injection
• QIV
Intramuscular injection
• bIRV
Intramuscular injection
• tIRV
Intramuscular injection

Locations

Country	Name	City	State
United States	North Alabama Research Center	Athens	Alabama
United States	The Heart Center	Athens	Alabama
United States	Pradeep Chandra, DO, FACC	Bridgeton	Missouri
United States	Charlottesville Medical Research	Charlottesville	Virginia
United States	Clinical Research Professionals	Chesterfield	Missouri
United States	Great Lakes Clinical Trials - Ravenswood	Chicago	Illinois
United States	CTI Clinical Research Center	Cincinnati	Ohio
United States	Centricity Research Columbus Ohio Multispecialty	Columbus	Ohio
United States	Velocity Clinical Research, Providence	East Greenwich	Rhode Island
United States	Retina Associates	Elmhurst	Illinois
United States	Michigan Center of Medical Research (MICHMER)	Farmington Hills	Michigan
United States	Proactive Clinical Research,LLC	Fort Lauderdale	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	Finlay Medical Research	Greenacres City	Florida
United States	Indago Research & Health Center, Inc	Hialeah	Florida
United States	Research Centers of America ( Hollywood )	Hollywood	Florida
United States	East-West Medical Research Institute	Honolulu	Hawaii
United States	Prolato Clinical Research Center	Houston	Texas
United States	Alliance for Multispecialty Research, LLC	Knoxville	Tennessee
United States	Alliance for Multispecialty Research, LLC	Knoxville	Tennessee
United States	Orange County Research Center	Lake Forest	California
United States	Pioneer Heart Institute	Lincoln	Nebraska
United States	Main Street Physician's Care	Little River	South Carolina
United States	McLeod Cardiology Associates - Little River	Little River	South Carolina
United States	Angels Clinical Research Institute	Miami	Florida
United States	Entrust Clinical Research	Miami	Florida
United States	Gerardo Polanco, MD	Miami	Florida
United States	Jackson Medical Group Cardiac Care	Miami	Florida
United States	Miami Clinical Research	Miami	Florida
United States	Miami Dade Medical Research Institute, LLC	Miami	Florida
United States	Research Institute of South Florida	Miami	Florida
United States	Palm Springs Community Health Center	Miami Lakes	Florida
United States	Palm Springs Community Health Center	Miami Lakes	Florida
United States	Panax Clinical Research	Miami Lakes	Florida
United States	Monroe Biomedical Research	Monroe	North Carolina
United States	Affinity Health	Oak Brook	Illinois
United States	Alliance for Multispecialty Research, LLC	Oak Brook	Illinois
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Quality Clinical Research	Omaha	Nebraska
United States	Velocity Clinical Research, Omaha	Omaha	Nebraska
United States	Orange County Heart Institute	Orange	California
United States	Innovation Medical Research Center	Palmetto Bay	Florida
United States	DBC Research USA	Pembroke Pines	Florida
United States	HOPE Research Institute	Phoenix	Arizona
United States	The Pain Center of Arizona	Phoenix	Arizona
United States	United Medical Research	Port Orange	Florida
United States	ActivMed Practices & Research, LLC.	Portsmouth	New Hampshire
United States	M3 Wake Research, Inc.	Raleigh	North Carolina
United States	Sundance Clinical Research	Saint Louis	Missouri
United States	California Research Foundation	San Diego	California
United States	Savannah Medical Group	Savannah	Georgia
United States	Velocity Clinical Research, Savannah	Savannah	Georgia
United States	Jadestone Clinical Research	Silver Spring	Maryland
United States	Clinical Research Atlanta	Stockbridge	Georgia
United States	SUNY Upstate Medical University Institute for Global Health	Syracuse	New York
United States	DM Clinical Research	Tomball	Texas
United States	Orange County Research Center	Tustin	California
United States	Alliance for Multispecialty Research, LLC	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
BioNTech SE	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SSA: Percentage of participants reporting local reactions	Pain at the injection site, redness, and swelling, as self-reported in electronic diaries.	For 7 days after vaccination
Primary	SSA: Percentage of participants reporting systemic events	Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain, as self-reported in electronic diaries.	For 7 days after vaccination
Primary	SSA: Percentage of participants reporting adverse events	As elicited by investigational site staff.	For 4 weeks after vaccination
Primary	SSA: Percentage of participants reporting serious adverse events	As elicited by investigational site staff.	For 6 months after vaccination
Primary	SSA: Percentage of participants with abnormal troponin I laboratory values	As measured at the central laboratory	2 days after vaccination
Primary	SSA: Percentage of participants with abnormal troponin I laboratory values	As measured at the central laboratory	1 week after vaccination
Primary	SSA: Percentage of participants with new electrocardiogram (ECG) abnormalities	ECG abnormalities consistent with probable or possible myocarditis or pericarditis, as judged by a cardiologist	2 days after vaccination
Primary	SSA: Percentage of participants with new ECG abnormalities	ECG abnormalities consistent with probable or possible myocarditis or pericarditis, as judged by a cardiologist	1 week after vaccination
Primary	SSB Initial Enrollment: Percentage of participants with abnormal troponin I laboratory values	Measured at the central laboratory	2 days after vaccination
Primary	SSB Initial Enrollment: Percentage of participants with abnormal troponin I laboratory values	As measured at the central laboratory	1 week after vaccination
Primary	SSB Initial Enrollment: Percentage of participants with new electrocardiogram (ECG) abnormalities	ECG abnormalities consistent with probably or possible myocarditis or pericarditis as judged by a cardiologist	2 days after vaccination
Primary	SSB Initial Enrollment: Percentage of participants with new electrocardiogram (ECG) abnormalities	ECG abnormalities consistent with probably or possible myocarditis or pericarditis as judged by a cardiologist	1 week after vaccination
Primary	SSB: Percentage of participants reporting local reactions	Pain at the injection site, redness, and swelling, as self-reported in electronic diaries.	For 7 days after vaccination
Primary	SSB: Percentage of participants reporting systemic events	Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain, as self-reported in electronic diaries.	For 7 days after vaccination
Primary	SSB: Percentage of participants reporting adverse events	As elicited by investigational site staff.	For 4 weeks after vaccination
Primary	SSB: Percentage of participants reporting serious adverse events	As elicited by investigational site staff.	For 6 months after vaccination
Secondary	SSA: Geometric Mean Titers (GMTs) of hemagglutination inhibition (HAI) titers	As measured at the central laboratory	At baseline, and 1-, 4-, and 8-weeks after vaccination
Secondary	SSA: Geometric Mean Fold Rise (GMFRs) of HAI titers	As measured at the central laboratory	At baseline, and 1-, 4-, and 8-weeks after vaccination
Secondary	SSA: Proportion of participants achieving HAI seroconversion for each strain	As measured at the central laboratory	At 1-, 4-, and 8-weeks after vaccination
Secondary	SSA: Percentage of participants with HAI titers = 1:40 for each strain	As measured at the central laboratory	Before vaccination and at 1-, 4-, 8-weeks after vaccination
Secondary	SSA: Percentage of participants achieving HAI seroconversion for all strains	As measured at the central laboratory	At 1-, 4-, 8-weeks after vaccination
Secondary	SSA: Percentage of participants with HAI =1:40 for all strains	As measured at the central laboratory	At 1-, 4-, 8-weeks after vaccination
Secondary	SSA: GMTs of SARS-CoV-2 Omicron (BA.4/BA.5)-neutralizing titers and SARS-CoV-2 reference-strain-neutralizing titers	As measured at the central laboratory	At 1-, 4-, and 8 weeks after vaccination
Secondary	SSA: GMFRs of SARS-CoV-2 Omicron (BA.4/BA.5)-neutralizing titers and SARS-CoV-2 reference-strain-neutralizing titers	As measured at the central laboratory	At 1-, 4-, and 8 weeks after vaccination
Secondary	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	As measured at the central laboratory	At 1-, 4-, and 8 weeks after vaccination.
Secondary	SSB: Geometric Mean Titers (GMTs) of hemagglutination inhibition (HAI) titers	As measured at the central laboratory	Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination
Secondary	SSB: Geometric Mean Fold Rise (GMFRs) of HAI titers	As measured at the central laboratory	Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination
Secondary	SSB: Proportion of participants achieving HAI seroconversion for each strain	As measured at the central laboratory	Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination
Secondary	SSB: Percentage of participants with HAI titers = 1:40 for each strain	As measured at the central laboratory	Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination
Secondary	SSB: Percentage of participants achieving HAI seroconversion for all strains	As measured at the central laboratory	Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination
Secondary	SSB: Percentage of participants with HAI =1:40 for all strains	As measured at the central laboratory	Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination
Secondary	SSB: GMTs of SARS-CoV-2 Omicron (BA.4/BA.5)-neutralizing titers and SARS-CoV-2 reference-strain-neutralizing titers	As measured at the central laboratory	Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination
Secondary	SSB: GMFRs of SARS-CoV-2 Omicron (BA.4/BA.5)-neutralizing titers and SARS-CoV-2 reference-strain-neutralizing titers	As measured at the central laboratory	Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination
Secondary	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	As measured at the central laboratory	Initial: At baseline and 4 weeks after vaccination. Expanded: At baseline, 4 weeks and 6 months after vaccination

External Links

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