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

COVID-19 Prevention Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05091307
• Other study ID #: CR109083
• Secondary ID: 2021-003953-43VA
• Status: Completed
• Phase: Phase 3
• Start date: November 2, 2021
• Est. completion date: November 15, 2022

Study information

• Verified date: January 2024
• Source: Janssen Vaccines & Prevention B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 861
• Est. completion date: November 15, 2022
• Est. primary completion date: June 17, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19 Prevention

Intervention

Biological:
• Ad26.COV2.S
Ad26.COV2.S will be administered as an IM injection.

Other:
• Placebo
Placebo will be administered as an IM injection.

Biological:
• Influenza Vaccine
Influenza vaccine high and standard dose will be administered as IM injection.

Locations

Country	Name	City	State
Belgium	Anima	Alken
Belgium	Institute of Tropical Medicine Antwerp	Antwerpen
Belgium	Clinical Pharmacology Unit	Merksem
Belgium	Private Practice RESPISOM Namur	Namur
Poland	Synexus Polska Sp. z o.o. Oddzial w Czestochowie	Czestochowa
Poland	Gdanskie Centrum Zdrowia	Gdansk
Poland	Synexus Polska Sp. z o.o. Oddzial w Gdansku	Gdansk
Poland	Synexus Polska Sp. z o.o. Oddzial w Gdynia	Gdynia
Poland	Synexus Polska Sp. z o.o. Oddzial w Katowicach	Katowice
Poland	Synexus Polska Sp. z o.o. Oddzial w Lodzi	Lodz
Poland	Synexus Polska Sp. z.o.o. Oddzial w Poznaniu	Poznan
Poland	Centrum Medyczne Pratia Poznan	Skorzewo
Poland	Synexus Polska Sp. z o.o. Oddzial w Warszawie	Warszawa
Poland	Synexus Polska Sp. z o.o. Oddzial we Wroclawiu	Wroclaw
United States	Clinical Research of South Florida, an AMR Company	Coral Gables	Florida
United States	Medisphere Medical Research Center, Llc	Evansville	Indiana
United States	Carolina Institute for Clinical Research	Fayetteville	North Carolina
United States	AMR Fort Myers Clinical Physiology Associates, an AMR company	Fort Myers	Florida
United States	I.D. Care, Inc.	Hillsborough	New Jersey
United States	Ventavia Research Group, LLC	Keller	Texas
United States	Clinical Research Consortium, an AMR company	Las Vegas	Nevada
United States	Office of Emilio Mantero-Atienza, MD	Miami	Florida
United States	Premier Research Associate, Inc	Miami	Florida
United States	University of Miami Health System	Miami	Florida
United States	Meridian Clinical Research, LLC	Norfolk	Nebraska
United States	Coastal Carolina Research Center	North Charleston	South Carolina
United States	Research Your Health	Plano	Texas
United States	Clinical Research Partners, LLC	Richmond	Virginia
United States	Rochester Clinical Research, Inc	Rochester	New York
United States	Wr-McCr, Llc	San Diego	California
United States	Fiel Family and Sports Medicine Clinical Research Advantage	Tempe	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Vaccines & Prevention B.V.

Countries where clinical trial is conducted

United States,  Belgium,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)