A Study of Ad26.COV2.S and Influenza Vaccines in Healthy Adults

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the non-inferiority (NI) of the humoral immune response of the 4 influenza vaccine strains after concomitant administration of the Ad26.COV2.S vaccine and a seasonal quadrivalent standard-dose influenza vaccine versus the administration of a seasonal quadrivalent standard-dose influenza vaccine administered alone; and to demonstrate the NI of the binding antibody response after concomitant administration of Ad26.COV2.S vaccine and a seasonal quadrivalent standard-dose influenza vaccine versus the administration of Ad26.COV2.S vaccine administered alone.

Detailed Description
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Severe acute respiratory syndrome coronavirus(-2) (SARS CoV-2) is a highly transmissible and pathogenic coronavirus that has spread rapidly and globally and Influenza is a worldwide public health problem, responsible for significant morbidity and mortality. Ad26.COV2.S (also known as VAC31518, JNJ-78436735) is a monovalent vaccine composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector, constructed to encode SARS-CoV-2 spike (S) protein, stabilized in its prefusion conformation. The seasonal influenza vaccines to be used in this study are quadrivalent (standard dose) and quadrivalent (high-dose) or equivalent formulated. The aim is to demonstrate the concomitant administration of the Ad26.COV2.S vaccine and a seasonal quadrivalent influenza vaccine (standard-dose) is non-inferior than the administration of either seasonal quadrivalent influenza vaccine (standard-dose) alone as measured by HI titers against each of the 4 influenza vaccine strains at 28 days after the administration of a quadrivalent seasonal influenza vaccine or Ad26.COV2.S vaccine alone as measured by Spiked-Enzyme-linked Immunosorbent Assay (S-ELISA) antibody titers at 28 days after the administration of the Ad26.COV2.S vaccine. This study consists of 3 phases: screening phase (Day -28 to 1), treatment phase (vaccination visits on Days 1 and 29), and a follow-up phase (28 days after each vaccination). Some of safety assessments will include physical examination, vital signs, clinical safety laboratory assessments, pregnancy testing, monitoring of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESI). The total duration of the study is up to 7-8 months. Note: The Informed Consent Form dated 25-Mar-2022 is final version of the study MASTER ICF, used by local countries to prepare the local language version of the ICF, which have been approved by the Ethics Committees. And the highlighted text in the ICF document are the guidance for country specific adaptation.

Official Title
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A Randomized, Double-blind, Phase 3 Study to Evaluate Safety, Reactogenicity, and Immunogenicity of Co-administration of Ad26.COV2.S and Influenza Vaccines in Healthy Adults 18 Years of Age and Older

Conditions
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COVID-19 Prevention

Intervention / Treatment
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* Biological: Ad26.COV2.S
* Other: Placebo
* Biological: Influenza Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be healthy, in the investigator's clinical judgment, as confirmed by medical history, physical examination, and vital signs performed at screening. Participants may have underlying illnesses, as long as the symptoms and signs are medically controlled Participant either received complete primary vaccination with an authorized/licensed coronavirus disease-2019 (COVID-19) vaccine (completed greater than or equal to [>=] 6 months prior to the last vaccination received against COVID-19) or is COVID-19 vaccine-naive All participants who were born female and are of childbearing potential must: a. Have a negative highly sensitive urine pregnancy test at screening, b. Have a negative highly sensitive urine pregnancy test on the day of vaccination prior to each study vaccine administration Participant agrees to not donate or receive bone marrow, blood, and blood products from the administration of the study vaccine until 3 months after receiving the study vaccines Participant must be willing to provide verifiable identification to be contacted and to contact the investigator during the study Exclusion Criteria: Participant has a history of malignancy within 1 year before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancies considered cured with minimal risk of recurrence per investigator's clinical judgment) Participant has a clinically significant acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature >= 38.0 degrees celsius (ºC) (100.4 degrees fahrenheit [°F]) within 24 hours prior to the planned dose of study vaccine; randomization at a later date is permitted at the discretion of the investigator Participant has history of thrombosis with thrombocytopenia syndrome (TTS) or heparin-induced thrombocytopenia and thrombosis (HITT) Participant has history of capillary leak syndrome Participant received a licensed/registered severe acute respiratory syndrome coronavirus(-2) (SARS-CoV-2) vaccine less than 6 months prior to first study vaccination (other than study vaccination) Participant has a history of any neurological disorders or seizures including Guillain-Barre syndrome, with the exception of febrile seizures during childhood

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Ad26.COV2.S + Quadrivalent (Q) Standard-dose (SD) Influenza Vaccine and Placebo<br>Participants aged greater than or equal to (>=) 18 years will receive a single intramuscular (IM) injection of Ad26.COV2.S and a seasonal Q SD influenza vaccine on Day 1 and placebo on Day 29. | Biological: Ad26.COV2.S<br>* Ad26.COV2.S will be administered as an IM injection.<br>* Other names: JNJ-78436735;Other: Placebo<br>* Placebo will be administered as an IM injection.<br>Biological: Influenza Vaccine<br>* Influenza vaccine high and standard dose will be administered as IM injection.<br>|
| Placebo Comparator: Group 2: Placebo + Q SD Influenza Vaccine and Ad26.COV2.S<br>Participants aged >=18 years will receive a single IM injection of placebo and a seasonal Q SD influenza vaccine on Day 1 followed by Ad26.COV2.S on Day 29. | Biological: Ad26.COV2.S<br>* Ad26.COV2.S will be administered as an IM injection.<br>* Other names: JNJ-78436735;Other: Placebo<br>* Placebo will be administered as an IM injection.<br>Biological: Influenza Vaccine<br>* Influenza vaccine high and standard dose will be administered as IM injection.<br>|
| Experimental: Group 3: Ad26.COV2.S + Q High-dose (HD) Influenza Vaccine and Placebo<br>Participants aged >=65 years will receive a single IM injection of Ad26.COV2.S and a seasonal Q HD influenza vaccine on Day 1 followed by placebo on Day 29. | Biological: Ad26.COV2.S<br>* Ad26.COV2.S will be administered as an IM injection.<br>* Other names: JNJ-78436735;Other: Placebo<br>* Placebo will be administered as an IM injection.<br>Biological: Influenza Vaccine<br>* Influenza vaccine high and standard dose will be administered as IM injection.<br>|
| Placebo Comparator: Group 4: Placebo + Q HD Influenza Vaccine and Ad26.COV2.S<br>Participants aged >=65 years will receive a single IM injection of placebo and a seasonal Q HD influenza vaccine on Day 1 followed by Ad26.COV2.S on Day 29. | Biological: Ad26.COV2.S<br>* Ad26.COV2.S will be administered as an IM injection.<br>* Other names: JNJ-78436735;Other: Placebo<br>* Placebo will be administered as an IM injection.<br>Biological: Influenza Vaccine<br>* Influenza vaccine high and standard dose will be administered as IM injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Groups 1 and 2: Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibodies Against Each of the Four Influenza Vaccine Strains 28 Days After the Administration of a Seasonal Quadrivalent Standard-dose Influenza Vaccine | GMTs of HI antibodies were measured using hemagglutination inhibition (HAI) assay against each of four influenza vaccine strains (A/Victoria [H1N1], A/Cambodia [H3N2], B/Victoria [B/Victoria] and B/Phuket [B/Yamagata]). This outcome measure was planned to be analyzed for specified arms only. PPII=Per-protocol influenza immunogenicity. | 28 days after vaccination with seasonal quadrivalent standard-dose influenza vaccine (Day 29) | 
| Groups 1 and 2: Geometric Mean Concentrations (GMCs) of Antibodies Measured by Spiked-Enzyme-linked Immunosorbent Assay (S-ELISA) 28 Days After Administration of Ad26.COV2.S Vaccine | GMCs of antibody titers measured by S-ELISA at 28 days after administration of Ad26.COV2.S vaccine was reported. This outcome measure was planned to be analyzed for specified arms only. Seronegative participants (at Day 1) who became serology positive during the study, participants with positive molecular test for severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) and major protocol deviation were excluded from PPSI analysis. | 28 days after vaccination with Ad26.COV2.S vaccine (Group 1: Day 29, Group 2: Day 57) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Solicited Local Adverse Events (AEs) up to 7 Days After Each Vaccination | An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Solicited local AEs were defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs included erythema, swelling/induration, and pain/tenderness. | 7 days after first vaccination on Day 1 (up to Day 8); 7 days after second vaccination on Day 29 (up to Day 36) | 
| Number of Participants With Solicited Systemic AEs up to 7 Days After Each Vaccination | An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Solicited systemic AEs included fever (defined as body temperature of 38.0-degree celsius or higher), headache, fatigue, myalgia, nausea, vomiting were collected within 7 days after each vaccination. | 7 days after first vaccination on Day 1 (up to Day 8); 7 days after second vaccination on Day 29 (up to Day 36) | 
| Number of Participants With Unsolicited AEs up to 28 Days After Each Vaccination | An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Unsolicited AEs were all AEs for which the participant is not specifically questioned in the participant diary. | 28 days after first vaccination on Day 1 (up to Day 29); 28 days after second vaccination on Day 29 (up to Day 57) | 
| Number of Participants With Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. SAE was any untoward medical occurrence that at any dose results in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important. | From Day 1 (post-vaccination) to end of the study (up to 12.5 months) | 
| Number of Participants With Medically-attended Adverse Events (MAAEs) | Number of participants with MAAEs was reported. MAAEs were defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. New onset of chronic diseases was collected as part of the MAAEs. | From Day 1 (post-vaccination) to end of the study (up to 12.5 months) | 
| Number of Participants With Adverse Events of Special Interest (AESIs) | Number of participants with AESIs was reported. AESIs were significant AEs that were judged to be of special interest because of clinical importance, known or suspected class effects, or based on nonclinical signals. Thrombosis with Thrombocytopenia Syndrome (TTS), a syndrome characterized by a combination of both a thrombotic event and thrombocytopenia, was considered to be an AESI in this study. A suspected TTS case was defined as: Thrombotic events: suspected deep vessel venous or arterial thrombotic events; Thrombocytopenia, defined as platelet count below 150,000/microliter. | From Day 1 (post-vaccination) to end of the study (up to 12.5 months) | 
| Number of Participants With AEs Leading to Withdrawal From the Study | Number of participants with AE leading to withdrawal from the study was reported. | From Day 1 (post-vaccination) to end of the study (up to 12.5 months) | 
| Groups 3 and 4: GMTs of HI Antibodies Against Each of the Four Influenza Vaccine Strains 28 Days After the Administration of a Seasonal Quadrivalent High-dose Influenza Vaccine | GMTs of HI antibodies were measured using hemagglutination inhibition (HAI) assay against each of four influenza vaccine strains (A/Victoria [H1N1], A/Tasmania[H3N2], B/Washington [B/Victoria] and B/Phuket [B/Yamagata]). This outcome measure was planned to be analyzed for specified arms only. | 28 days after vaccination with seasonal quadrivalent high-dose influenza vaccine (Day 29) | 
| Group 3 and 4: GMCs of Antibodies Measured by S-ELISA 28 Days After Administration of Ad26.COV2.S Vaccine | GMCs of antibody titers measured by S-ELISA at 28 days after administration of Ad26.COV2.S vaccine was reported. This outcome measure was planned to be analyzed for specified arms only. Seronegative participants (at Day 1) who became serology positive during the study, participants with positive molecular test for SARSCoV-2 and major protocol deviation were excluded from PPSI analysis. | 28 days after vaccination with Ad26.COV2.S vaccine (Group 3: Day 29, Group 4: Day 57) | 
| GMCs of Antibodies Measured by S-ELISA 28 Days After Administration of Ad26.COV2.S Vaccine in COVID-19 Vaccine Naive Participants | GMCs of antibodies measured by S-ELISA 28 days after administration of Ad26.COV.S vaccine in Covid-19 vaccine naive participants was reported. In the below data table, '0' in the number analyzed field signifies that none of the participants were evaluable at the specified timepoint. | 28 days after the administration of Ad26.COV2.S vaccine (that is, for Groups 1 and 3: Day 29; for Groups 2 and 4: Day 57) | 
| Percentage of Participants With Seroconversion for Each of the 4 Influenza Vaccine Strains at 28 Days After the Administration of a Seasonal Quadrivalent (High-dose and Standard-dose) Influenza Vaccine | Seroconversion was defined for each of the 4 influenza vaccine strains (For group 1 and 2: A/Victoria [H1N1], A/Cambodia [H3N2], B/Victoria [B/Victoria], B/Phuket [B/Yamagata]; For group 3 and 4: A/Victoria [H1N1], B/Phuket (B/Yamagata), A/Tasmania [H3N2], B/Washington [B/Victoria]) at 28 days after the administration of a seasonal quadrivalent (high-dose and standard-dose) influenza vaccine: HI titer greater than or equal to (>=) 1:40 in participants with a pre-vaccination HI titer of less than (<) 1:10, or a >=4-fold HI titer increase in participants with a pre-vaccination HI titer of >= 1:10. In the below data table, '0' in the number analyzed field signifies that none of the participants were evaluable at the specified timepoint. | 28 days after the administration of a seasonal quadrivalent influenza vaccine (Day 29) | 
| Percentage of Participants With Seroprotection for Each of the 4 Influenza Vaccine Strains as HI Titer >= 1:40 at 28 Days After the Administration of a Seasonal Quadrivalent (High-dose and Standard-dose) Influenza Vaccine | Seroprotection was defined for each of the 4 influenza vaccine strains (For group 1 and 2: A/Victoria [H1N1], A/Cambodia [H3N2], B/Victoria [B/Victoria], B/Phuket [B/Yamagata]; For group 3 and 4: A/Victoria [H1N1], B/Phuket (B/Yamagata), A/Tasmania [H3N2], B/Washington [B/Victoria]) as HI titer >=1:40 at 28 days after the administration of a seasonal quadrivalent (high-dose and standard-dose) influenza vaccine. In the below data table, '0' in the number analyzed field signifies that none of the participants were evaluable at the specified timepoint. | 28 days after the administration of a seasonal quadrivalent influenza vaccine (Day 29) |