Evaluation of Immunogenicity, Safety, and Reactogenicity of JNJ-78901563 and High-Dose Quadrivalent Influenza Vaccine in Adults Aged 65 Years or Older
- Trial ID
- 2023-504168-40-00
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 3 randomized double-blind controlled study is to demonstrate the **non-inferiority** of the humoral immune response to the four influenza vaccine strains following the concomitant administration of ExPEC9V and a high-dose quadrivalent seasonal influenza vaccine, compared to the administration of the high-dose quadrivalent seasonal influenza vaccine alone. This is clinically relevant as it evaluates the potential for co-administration of vaccines in adults aged 65 years or older, which could enhance vaccination strategies and improve protection against both influenza and invasive extraintestinal pathogenic **Escherichia coli** (ExPEC) disease in this vulnerable population.
Participants
The clinical trial involves a total of **532 participants** who are being studied for the **prevention of invasive extraintestinal pathogenic Escherichia coli (ExPEC) disease**. The study population includes both male and female subjects, aged **65 years and older**, who are medically stable at the time of vaccination. Participants were selected based on their ability to work with smartphones, tablets, or computers, and their willingness to adhere to lifestyle restrictions specified in the protocol. The trial does not include a vulnerable population. Participants are required to be postmenopausal or surgically sterile, and they must not intend to conceive. They must also agree not to donate blood from the time of vaccination until three months after receiving the last dose of the study vaccine. The selection criteria ensure that participants are capable of reading, understanding, and completing an electronic diary, and they must provide verifiable identification and have the means to contact the investigator during the study.
Plans and Procedures
The clinical trial is a **Phase 3 randomized, double-blind, controlled study** designed to evaluate the immunogenicity, safety, and reactogenicity of ExPEC9V and a high-dose quadrivalent influenza vaccine, with and without co-administration, in adults aged 65 years or older. The primary objective is to demonstrate the non-inferiority of the humoral immune response to the four influenza vaccine strains after concomitant administration of ExPEC9V and a high-dose quadrivalent seasonal influenza vaccine compared to the administration of the high-dose quadrivalent seasonal influenza vaccine alone. The trial is expected to conclude by December 23, 2024, with recruitment starting on October 16, 2023.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, medical stability, and ability to adhere to study requirements. Following successful screening, participants will be randomized to receive either the investigational products or control. The study involves intramuscular administration of the vaccines, with a maximum treatment period of one day. Follow-up visits will occur to monitor safety and collect data on immunogenicity, with the primary endpoint being the measurement of antibody hemagglutination inhibition titers 29 days post-vaccination. The end-of-study visit will finalize data collection and ensure participant safety.
Participant involvement is expected to last until the end of the follow-up period, approximately 29 days post-vaccination. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or any situation where continued participation is deemed unsafe by the investigator. The study is conducted under strict adherence to ethical guidelines and regulatory requirements, ensuring the safety and well-being of all participants throughout the trial duration.
Treatment
The clinical trial involves the administration of three distinct treatments. The first treatment is **Isotone Natriumchloridlösung 0.9% Braun Injektionslösung**, a **solution for injection** containing **sodium chloride** as the active substance. This product is manufactured by B.BRAUN MELSUNGEN AG and is classified under the ATC code V07AB, which denotes solvents and diluting agents, including irrigating solutions. The solution is administered via **intramuscular use** with a maximum daily dose of 4.5 mg. The treatment period is limited to one day, ensuring that the total dose does not exceed the daily maximum. This product serves as a non-experimental treatment in the study, likely functioning as a placebo or comparator treatment.
The second treatment is **EFLUELDA**, a quadrivalent influenza vaccine provided as a **suspension for injection** in a pre-filled syringe. This vaccine, produced by SANOFI PASTEUR, contains multiple active substances, including B/Phuket/3073/2013-like virus, A/Victoria/2570/2019 (H1N1)pdm09-like strain, Influenza virus B/Michigan/01/2021, and Influenza virus A/Darwin/9/2021 IVR-228 (H3N2). The vaccine is administered intramuscularly with a maximum daily dose of 240 µg, and the treatment period is also restricted to one day. This vaccine is used as a standard-of-care therapy in the study, serving as a comparator to evaluate the immunogenicity and safety of the experimental vaccine.
The third treatment is the experimental vaccine **JNJ-78901563**, a **solution for injection** developed by JANSSEN VACCINES & PREVENTION B.V. This vaccine comprises multiple structurally diverse substances, including ECOO1A, ECOO2, ECOO4, ECOO6A, ECOO15, ECOO16, ECOO18A, ECOO25B, and ECOO75. The vaccine is administered via intramuscular injection with a maximum daily dose of 88 µg, and the treatment period is limited to one day. The primary objective of the trial is to assess the non-inferiority of the humoral immune response to the influenza vaccine strains when co-administered with JNJ-78901563 compared to the administration of the high-dose quadrivalent influenza vaccine alone. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the **antibody hemagglutination inhibition (HI) titers** against each of the four influenza vaccine strains. These titers will be measured using the HI assay 29 days after the administration of a high-dose (HD) quadrivalent seasonal influenza vaccine. Additionally, antibody titers to vaccine O-serotype antigens will be determined by a multiplex ECL-based immunoassay 29 days following the administration of ExPEC9V. These primary endpoints are designed to demonstrate the non-inferiority of the humoral immune response when ExPEC9V is co-administered with the HD quadrivalent influenza vaccine compared to the administration of the HD quadrivalent influenza vaccine alone.
Inclusion and Exclusion Criteria
Inclusion Criteria
- ≥65 years ofage, inclusive, on the day of signing the ICF
- must be medically stable at the time ofvaccination such that, according to the judgment of the investigator, hospitalization within the study period is not anticipated and the participant appears likely to be able to remain on study through the end of protocol- specified follow-up. A stable medical condition is defined as disease not requiring significant change in therapy during the 6 weeks before enrollment and when hospitalization for worsening of the disease is not anticipated. Participants will be included on the basis of physical examination, medical history, and vital signs performed between ICF signature and vaccination.
- Male or female
- before randomization, a participant must be: a.postmenopausal (postmenopausal state is defined as no menses for 12 months without an alternative medical cause); and b.not intending to conceive by any methods. Note: Surgically sterile participants are also eligible for the study.
- must sign an ICF indicating that the participant understands the purpose, procedures and potential risks and benefits ofthe study, and is willing to participate in the study.
- willing and able to adhere to the lifestyle restrictions specified in this protocol.
- agrees to not donate blood from the time of vaccination until 3 months after receiving the last dose of study vaccine.
- must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study.
- must be able to read, understand, and complete the eDiary.
- must be able to work with smartphones/tablets/computers.
Exclusion Criteria
- history of an underlying clinically significant acute or uncontrolled chronic medical condition or significant cognitive impairment or physical examination findings for which, in the opinion ofthe investigator, participation would not be in the best interest ofthe participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
- abnormal function of the immune system resulting from: a. clinical conditions or their treatments expected to have an impact on the immune response elicited by the study vaccine. Participants with clinical conditions that are stable under treatment without the use of prohibited therapies may be enrolled at the discretion of the investigator. b. chronic or recurrent use of systemic corticosteroids within 3 months before administration of study vaccine and during the study. A substantially immunosuppressive steroid dose is considered to be ≥2 weeks of daily receipt of 20 mg of prednisone or equivalent. Note: Ocular, topical or inhaled steroids are allowed. c. administration of antineoplastic and immunomodulating agents (eg, cancer chemotherapeutic agents) or radiotherapy expected to have an impact on the immune response elicited by the study vaccine within 6 months before administration of study vaccine and during the study.
- history of malignancy within 5 years before screening not in the following categories: a. participants with squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix may be enrolled at the discretion ofthe investigator. b. participants with a history of malignancy within 5 years before screening, with minimal risk of recurrence per investigator’s judgement, can be enrolled. c. participants with a diagnosis of localized prostate cancer may be enrolled at the discretion ofthe investigator ifthey completed treatment (continuation of androgen deprivation therapy is allowed) or if they remain under observation or active surveillance. Participants who underwent radical prostatectomy or radiotherapy may be enrolled at the discretion ofthe investigator if treatment has been completed 6 months prior to the planned administration of the study vaccine.
- known or suspected allergy or history of severe allergic reaction, anaphylaxis, or other serious adverse reactions to vaccines or vaccine excipients (specifically the excipients ofthe study vaccine) (refer to Investigator's Brochure).
- history of severe allergic reactions (eg, anaphylaxis) to any component of the HD quadrivalent seasonal influenza vaccine, including egg protein, or following a previous dose ofany influenza vaccine.
- has had major surgery (per the investigator’s judgment) within 4 weeks before administration of the first study vaccine or will not have recovered from surgery per the investigator’s judgment at time ofvaccination.
- history of acute polyneuropathy (eg. Guillain-Barré syndrome) or chronic inflammatory demyelinating polyneuropathy.
- has had major psychiatric illness or drug or alcohol abuse which in the investigator’s opinion would compromise the participant’s safety or compliance with the study procedures.
- contraindication to IM injections and blood draws (eg, bleeding disorders).
- received hematopoietic stem cell transplant based on medical history, treatment with immunoglobulins in the 2 months, apheresis therapies in the 4 months, or blood products in the 3 months before the planned administration of the first dose of study vaccine or has any plans to receive such treatment during the study. Note: Given that not all immunoglobulins/monoclonal antibodies are expected to impact the vaccine-induced immune response, the investigator should contact the sponsor to discuss eligibility ofparticipants on immunoglobulin treatment.
- received or plans to receive: a. licensed live attenuated vaccines - within 28 days before or after planned administration ofthe first or subsequent study vaccinations. b. other licensed (not live) vaccines - within 14 days before or after planned administration of the first or subsequent study vaccinations. c. vaccination with a vaccine authorized for emergency use (eg, EUA, CMA, or a similar program) is permitted when given at least 28 days before or after planned administration of the first or subsequent study vaccinations.
- received vaccination with seasonal influenza vaccine for the current influenza season in the Northern Hemisphere.
- received any E. coli1 or ExPEC vaccine.
- received an investigational drug or used an invasive investigational medical device within 90 days, or received an investigational vaccine within 90 days before the planned administration of the first dose of study vaccine, or is currently enrolled or plans to participate in another investigational study during the course of this study and before 6 months after administration of the study vaccine.
- has uncontrolled HIV type 1 or type 2 infection. Note: a participant with a stable/well-controlled HIVinfection is allowed.
- has a diagnosis ofchronic active hepatitis B or hepatitis C infection that is not medically stable, based on judgement of the investigator. Note: a participant with a stable and virologically suppressed hepatitis B or hepatitis C infection is allowed.
- employee ofthe investigator or study site with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members ofthe employees or the investigator, or an employee ofthe sponsor or CRO.
- cannot communicate reliably with the investigator.
- who, in the opinion of the investigator, is unlikely to adhere to the requirements ofthe study, or is unlikely to complete the full course of vaccination and observation.
- who has significant scarring, tattoos, abrasions, cuts, or infections over the deltoid region of both arms that, in the investigator’s opinion, could interfere with evaluation of injection site local reactions.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 16 Oct 2023 | 150 |
 Poland | Not Recruiting | 16 Oct 2023 | 250 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Isotone Natriumchloridlösung 0,9 % Braun Injektionslösung | Placebo | INJEKTIONSLÖSUNG | INTRAMUSCULAR USE | 4.5 | 1 | PRD567881 |
EFLUELDA, suspension injectable en seringue préremplie
Vaccin grippal quadrivalent (virion fragmenté, inactivé), 60 microgrammes HA /souche | Test | SUSPENSION INJECTABLE EN SERINGUE PRÉREMPLIE | INTRAMUSCULAR USE | 240 | 1 | PRD8927350 |
JNJ-78901563 | Test | SOLUTION FOR INJECTION | INTRAMUSCULAR USE | 88 | 1 | PRD10295690 |