A Phase 3 Randomized Double-blind Controlled Study to Evaluate the Immunogenicity, Safety, and Reactogenicity of ExPEC9V and High-dose Quadrivalent Influenza Vaccine, With and Without Co-administration, in Adults Aged 65 Years or Older

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen Vaccines & Prevention B.V.

Participant type

Healthy volunteers

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

6 Nov 2023 → 27 Jul 2024

Decision date (initial)

2023-09-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others

To demonstrate the non-inferiority ofthe humoral immune response to the 4 influenza vaccine strains after concomitant administration ofExPEC9V and a high-dose (HD) quadrivalent seasonal influenza vaccine versus the administration ofa HD quadrivalent seasonal influenza vaccine administered alone.

Conditions and MedDRA coding

Prevention of invasive extraintestinal pathogenic Escherichia coli (ExPEC) disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. ≥65 years ofage, inclusive, on the day of signing the ICF
2. 2. 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.
3. 3. Male or female
4. 4. 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.
5. 5. 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.
6. 6. willing and able to adhere to the lifestyle restrictions specified in this protocol.
7. 7. agrees to not donate blood from the time of vaccination until 3 months after receiving the last dose of study vaccine.
8. 8. must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study.
9. 9. must be able to read, understand, and complete the eDiary.
10. 10. must be able to work with smartphones/tablets/computers.

Exclusion criteria 20

1. 1. 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
2. 2. 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.
3. 3. 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.
4. 4. 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).
5. 5. 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.
6. 6. 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.
7. 7. history of acute polyneuropathy (eg. Guillain-Barré syndrome) or chronic inflammatory demyelinating polyneuropathy.
8. 8. 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.
9. 9. contraindication to IM injections and blood draws (eg, bleeding disorders).
10. 10. 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.
11. 11. 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.
12. 12. received vaccination with seasonal influenza vaccine for the current influenza season in the Northern Hemisphere.
13. 13. received any E. coli1 or ExPEC vaccine.
14. 14. 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.
15. 15. has uncontrolled HIV type 1 or type 2 infection. Note: a participant with a stable/well-controlled HIVinfection is allowed.
16. 16. 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.
17. 17. 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.
18. 18. cannot communicate reliably with the investigator.
19. 19. 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.
20. 20. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Antibody hemagglutination inhibition (HI) titers as measured by HI assay against each of the 4 influenza vaccine strains, 29 days after the administration of a HD quadrivalent seasonal influenza vaccine. Antibody titers to vaccine O-serotype antigens, as determined by multiplex ECL-based immunoassay 29 days after administration of ExPEC9V.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen Vaccines & Prevention B.V.

Sponsor organisation

Janssen Vaccines & Prevention B.V.

Address

Archimedesweg 4-6

City

Leiden

Postcode

2333 CN

Country

Netherlands

Scientific contact point

Organisation

Janssen Vaccines & Prevention B.V.

Contact name

CTIS Point of Contact

Public contact point

Organisation

Janssen Vaccines & Prevention B.V.

Contact name

CTIS Point of Contact

Third parties 9

Locations

2 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications