A study to evaluate ExPEC9V vaccine for the prevention of Invasive E. coli Disease in adults aged 60 years and older with a history of urinary tract infection in the past two years.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen Vaccines & Prevention B.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

9 Feb 2022 → 28 Aug 2025

Decision date (initial)

2024-06-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Janssen Vaccines & Prevention B.V.

External identifiers

EU CT number

2023-506589-30-00

EudraCT number

2020-005273-27

ClinicalTrials.gov

NCT04899336

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Safety, Efficacy

To demonstrate the efficacy of ExPEC9V compared to placebo in the prevention of the first IED event with microbiological confirmation from blood or other sterile sites caused by ExPEC9V O-serotypes O1, O2, O4, O6, O15, O16, O18, O25, and O75

Secondary objectives 16

1. 2. To demonstrate the efficacy of ExPEC9V compared to placebo in the prevention of: •all IEDs caused by ExPEC9V O-serotypes
2. 3. To demonstrate the efficacy of ExPEC9V compared to placebo in the prevention of: •the first hospitalized IED event caused by ExPEC9V O-serotypes
3. 4. To demonstrate the efficacy of ExPEC9V compared to placebo in the prevention of: •the first IED event meeting criteria for sepsis caused by ExPEC9V O-serotypes
4. 5. To demonstrate the efficacy of ExPEC9V compared to placebo in the prevention of: •the first bacteremic IED event caused by ExPEC9V O-serotypes
5. 6. To demonstrate the efficacy of ExPEC9V compared to placebo in the prevention of: •the first pyelonephritis event caused by ExPEC9V O-serotypes
6. 7. To demonstrate the efficacy of ExPEC9V compared to placebo in the prevention of: •the first UTI event caused by ExPEC9V O-serotypes
7. 8. To demonstrate the efficacy of ExPEC9V compared to placebo in the prevention of: •all UTIs caused by ExPEC9V O-serotypes
8. 9. To demonstrate the efficacy of ExPEC9V compared to placebo in the prevention of: •the first IED event caused by E. coli
9. 10. To demonstrate the efficacy of ExPEC9V compared to placebo in the prevention of: •the first pyelonephritis event caused by E. coli
10. 11.To demonstrate the efficacy of ExPEC9V compared to placebo in the prevention of: •the first UTI event caused by E. coli
11. 12. To evaluate: •the immunogenicity of ExPEC9V in the Immunogenicity Subset
12. 13. To evaluate: •the safety and reactogenicity of ExPEC9V
13. 14. To evaluate: •the preservation of health status and health-related quality of life (HRQoL) of ExPEC9V compared to placebo
14. 15. To evaluate: •the impact of IED and UTI, caused by ExPEC9V O-serotypes, on physical and mental health, and overall HRQoL
15. 16. To evaluate the impact of pyelonephritis, caused by ExPEC9V O-serotypes, on physical and mental health, and overall HRQoL as measured by the SF-36 and the EQ-5D-5L
16. 1. To demonstrate the efficacy of ExPEC9V compared to placebo in the prevention of the first IED event, with microbiological confirmation from blood, other sterile sites, or urine, caused by ExPEC9V O-serotypes

Conditions and MedDRA coding

Invasive Extraintestinal Pathogenic Escherichia coli Disease

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinicaltrials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Participant must be ≥60 years of age on the day of signing the ICF and is expected to be available for the duration of the study, with no current intention of moving away from a study site area or travelling for periods longer than 30 consecutive days during the course of the study.
2. Participant must have a history of UTI in the past 2 years for which evidence of diagnosis was verified by the investigator. In case of a recent history of UTI or ABP (acute bacterial prostatitis), the condition must have resolved >14 days prior to randomization.
3. Participant must be medically stable at the time of vaccination 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.
4. Before randomization, participants who were born female must be either (as defined in Section 10.4, Appendix 4, Contraceptive Guidance and Collection of Pregnancy Information): a. postmenopausal or permanently sterile, and b. not intending to conceive by any methods.
5. Participant must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study.
6. Participant and his/her designated caregiver (if applicable) must be able to read, understand, and complete questionnaires in the electronic clinical outcome assessment system (eCOA, ie, the electronic patient-reported outcomes [ePROs] and the eDiary). If the participant and caregiver are unable/unwilling to work with the eCOA system to complete the ePROs, participant or caregiver must agree to be available to be contacted by the site to complete all eCOA activities (ePROs) via site-assisted interview at the timepoints specified in the protocol. Participants in the Safety Subset must be willing and able to work with the eCOA system to complete the eDiary.
7. Participant must have at least one additional risk factor for invasive extraintestinal pathogenic Escherichia coli disease (IED), beyond a history of urinary tract infection (UTI) in the past 2 years. Additional risk factors for IED are defined as one or more of the following: a. a history of urosepsis and/or E. coli bacteremia at any time prior to randomization, and/or b. a history of inpatient hospitalization (for a medical/surgical cause) in the two years prior to randomization, and/or c. presence at baseline of at least one risk factor for complicated UTI of any toxicity grade and / or d. a history of pyelonephritis of any toxicity grade that has resolved > 14 days prior to randomization, and/or e. current or prior prostatic adenocarcinoma and/or tumors of the urinary tract of any toxicity grade

Exclusion criteria 12

1. Participant has a serious chronic disorder or significant cognitive impairment for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise well-being) or that could prevent, limit, or confound the protocol-specified assessments.
2. Participant has end-stage renal disease for which dialysis is required.
3. Participant has a history of malignancy within 5 years before screening that does not include the following categories:(a) Participants with curatively treated squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix may be enrolled at the discretion of the investigator; (b) Participants with a diagnosis of localized prostate cancer may be enrolled at the discretion of the investigator if they completed treatment, or, if they remain under observation or active surveillance; Participants who underwent radical prostatectomy or radiotherapy may be enrolled at the discretion of the investigator if treatment has been completed 6 months prior to the planned administration of the study vaccine (c) Participants with a history of other malignancy within 5 years, which is considered adequately treated with minimal risk of recurrence per the investigator's judgment, may be enrolled.
4. Participant has a known history of severe allergic reaction, anaphylaxis or other serious adverse reactions to vaccines or vaccine excipients (including specifically the excipients of the study vaccine; refer to IB).
5. 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. 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 or more of prednisone or equivalent. c. Administration of antineoplastic and immunomodulating 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.
6. Participant has a history of acute polyneuropathy (eg, Guillain-Barré syndrome) or chronic inflammatory demyelinating polyneuropathy
7. Participant has received any E. coli or ExPEC vaccine.
8. Participant has received a hematopoietic stem cell transplant based on medical history, treatment with immunoglobulins within 2 months, apheresis therapies within 4 months, or blood products within 3 months prior to the planned administration of the study vaccine or has any plans to receive such treatment during the study.
9. Participant has received or plans to receive: (a)licensed live attenuated vaccines - within 28 days before or after planned administration of the study vaccination; (b)other licensed (not live) vaccines - within 14 days before or after planned administration of the study vaccination; (c)vaccination with a vaccine authorized for Emergency Use Authorization, conditional Marketing Authorisation or a similar program is permitted when given at least 28 days before or after planned administration of the study vaccination.
10. Participant has had major surgery (per the investigator's judgment) within 4 weeks before dosing or will not have recovered from surgery per the investigator's judgment at time of vaccination.
11. Participant has chronic active hepatitis B or hepatitis C infection based on medical history. Note: participant may have stable HBV or HCV infection.
12. Participant has evidence of HIV type 1 or type 2 infection by medical history. Note: participant may have stable/well-controlled HIV.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. First IED event, with microbiological confirmation from blood or other sterile sites, excluding IED cases with microbiological confirmation from urine only, caused by ExPEC9V O-serotypes O1, O2, O4, O6, O15, O16, O18, O25, and O75

Secondary endpoints 21

1. 2. All IEDs (including multiple IEDs per participant) caused by ExPEC9V O serotypes
2. 3. First hospitalized IED event caused by ExPEC9V O serotypes
3. 4. First IED event meeting criteria for sepsis caused by ExPEC9V O serotypes
4. 5. First bacteremic IED event caused by ExPEC9V O serotypes
5. 6. First pyelonephritis event caused by ExPEC9V O serotypes
6. 7. First UTI event caused by ExPEC9V O serotypes
7. 8. All UTIs (including multiple UTIs per participant) caused by ExPEC9V O serotypes
8. 9. First IED event caused by E. coli
9. 10. First pyelonephritis event caused by E. coli
10. 11. First UTI event caused by E. coli
11. 12. Antibody titers to vaccine O-serotype antigens and EPA in the Immunogenicity Subset, as determined by multiplex ECL-based immunoassay and antibody titers to vaccine O-serotype antigens, as determined by multiplex opsonophagocytic killing assay (MOPA) on Day 1 (pre-vaccination), Day 30, Day 181, Year 1, Year 2, Year 3 and Year 4
12. 13. Solicited local and systemic AEs (collected until 14 days postvaccination [from Day 1 to Day 15] in the Safety Subset)
13. 14. Unsolicited AEs (collected until 29 days post-vaccination [from Day 1 to Day 30] in all participants)
14. 15. Serious adverse events (SAEs) in all participants
15. 16. SF-36 and EQ-5D-5L responses at scheduled timepoints
16. 17. Frailty index as a measure of frailty at baseline, Year 1, Year 2, Year 3, Year 4 and at the time of an IED
17. 18. Medical resource utilization for IED events caused by ExPEC9V O-serotypes
18. 19. Medical resource utilization for UTI events (Immunogenicity Subset only) and ABP events (Immunogenicity Subset only) caused by ExPEC9V O-serotypes
19. 20. Hospitalization and length of stay in the hospital, including intensive care unit (ICU) hospitalization and ICU length of stay, for IED, UTI or ABP events caused by ExPEC9V O-serotypes
20. 21. IED-related and all-cause mortality
21. 1. First IED event, with microbiological confirmation from blood, other sterile sites, or urine, caused by ExPEC9V O-serotypes

Investigational products

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

Test 1

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 10

Locations

7 EU/EEA countries · 52 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

Documents 166 files

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

Application history

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