Study to Evaluate the Safety, Tolerability and Immunogenicity of a Potential Enteric Fever Vaccine

NCT ID: NCT04349553

Last Updated: 2025-08-17

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

46 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-12-16

Study Completion Date

2021-02-15

Brief Summary

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A Phase 1, randomised, double-blind, placebo-controlled, parallel group study in 45 healthy participants aged 18 to 45 years inclusive.

Detailed Description

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This is a Phase I, randomised, double-blind, placebo-controlled, parallel group, single-centre study involving 45 healthy participants. The aim is to evaluate the safety and immunogenicity of Entervax, a combination vaccine against enteric fever comprising Typhi ZH9 (hereafter ZH9) plus an engineered derivative that will provide an immune response to the key antigens (LPS 0:2 and H:a flagella) from S. Paratyphi A (hereafter ZH9PA). ZH9PA has not previously been tested in humans therefore the first two cohorts comprise a dose escalation of ZH9PA and the final cohort comprises a single dose level of the combination of ZH9PA and ZH9.

Conditions

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Enteric Fever

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Cohort 1 will consist of 9 participants, who will receive 3 doses of 1x10\^9 Colony Forming Units (CFU) of ZH9PA (6 participants) or placebo (3 participants).

Cohort 2 will consist of 18 participants, who will receive 3 doses of 1x10\^10 CFU of ZH9PA (12 participants) or placebo (6 participants).

Cohort 3 will consist of 18 participants, who will receive 3 doses of 1x10\^10 CFU of ZH9PA and 1x10\^10 CFU of ZH9 (12 participants) or placebo (6 participants).
Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators
Placebo

Study Groups

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ZH9PA 1x10^9 CFU

1mL ZH9PA 1x10\^9 CFU suspension in normal saline will be mixed with sodium bicarbonate 2%w/v to produce 150mL for oral administration

Group Type EXPERIMENTAL

Placebo

Intervention Type BIOLOGICAL

150mL vaccine for oral administration

ZH9PA

Intervention Type BIOLOGICAL

150mL vaccine for oral administration

ZH9PA 1x10^10 CFU

1mL ZH9PA 1x10\^10 CFU suspension in normal saline will be mixed with sodium bicarbonate 2%w/v to produce 150mL for oral administration

Group Type EXPERIMENTAL

Placebo

Intervention Type BIOLOGICAL

150mL vaccine for oral administration

ZH9PA

Intervention Type BIOLOGICAL

150mL vaccine for oral administration

ZH9PA 1x10^10 CFU plus ZH9 1x10^10 CFU

1mL ZH9PA 1x10\^10 CFU suspension in normal saline and 1mL ZH9 1x10\^10 CFU suspension in normal saline will be mixed with sodium bicarbonate 2%w/v to produce 150mL for oral administration

Group Type EXPERIMENTAL

ZH9PA and ZH9

Intervention Type BIOLOGICAL

150mL vaccine for oral administration

Placebo

Intervention Type BIOLOGICAL

150mL vaccine for oral administration

Placebo

1mL (Cohorts 1 and 2) or 2mL (Cohort 3) normal saline will be mixed with sodium bicarbonate 2%w/v to produce 150mL for oral administration

Group Type PLACEBO_COMPARATOR

ZH9PA and ZH9

Intervention Type BIOLOGICAL

150mL vaccine for oral administration

Placebo

Intervention Type BIOLOGICAL

150mL vaccine for oral administration

ZH9PA

Intervention Type BIOLOGICAL

150mL vaccine for oral administration

Interventions

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ZH9PA and ZH9

150mL vaccine for oral administration

Intervention Type BIOLOGICAL

Placebo

150mL vaccine for oral administration

Intervention Type BIOLOGICAL

ZH9PA

150mL vaccine for oral administration

Intervention Type BIOLOGICAL

Other Intervention Names

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Entervax

Eligibility Criteria

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Inclusion Criteria

To be confirmed at Screening

1. Healthy male and female participants 18 to 45 years of age, inclusive.
2. Female participant of childbearing potential willing to use 2 effective methods of contraception, i.e., established method of contraception + condom, if applicable (unless of non-childbearing potential or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the participant) from the first dose until 2 months after the last dose of Investigational Medicinal Product (IMP).
3. Female participant of non-childbearing potential. For the purposes of this study, this is defined as the participant being amenorrhoeic for at least 12 consecutive months or at least 4 months post-surgical sterilisation (including bilateral fallopian tube ligation or bilateral oophorectomy with or without hysterectomy).
4. Female participant of childbearing potential or non-childbearing potential with a negative pregnancy test at Screening.
5. Female participant of post-menopausal status confirmed by demonstrating at Screening that the serum level of the follicle stimulating hormone (FSH) falls within the respective pathology reference range. In the event a participant's menopausal status has been clearly established (for example, the participant indicates she has been amenorrhoeic for 10 years, confirmed by medical history, etc), but serum FSH levels are not consistent with a postmenopausal status, determination of the participant's eligibility to be included in the study will be at the Investigator's discretion following consultation with the Sponsor.
6. Male participant willing to use an effective method of contraception or 2 effective methods of contraception, i.e., established method of contraception + condom, if applicable (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the participant) from first dose until a stool sample tested for presence of the vaccine strains is negative.
7. Participant with a body mass index (BMI) of ≥ 19 or ≤34 kg/m\^2 (BMI = body weight (kg) / \[height (m)\]\^2).
8. No clinically significant history of liver or active gall bladder disease.
9. No clinically significant history of ongoing gastro-intestinal disease or abnormality.
10. No clinically significant history of previous allergy / sensitivity to ZH9/ZH9PA or sodium bicarbonate.
11. No clinically significant history of anaphylactic shock following vaccination.
12. No clinically significant history of hypersensitivity (e.g., hives/rash/swollen lips/difficulty with breathing) to azithromycin, ampicillin, trimethoprim-sulfamethoxazole or ciprofloxacin.
13. No clinically significant abnormal laboratory test results (in the opinion of the investigator) for serum biochemistry, haematology and/or urine analyses within 28 days before receiving the first dose administration of the IMP.
14. Participant with a negative urinary drugs of abuse (DOA) screen (including alcohol and cotinine) test results, determined within 28 days before the first dose administration of the IMP unless there is a documented medical explanation for the positive result other than drugs of abuse (e.g., the participant has been prescribed opioids for pain). (N.B.: A positive test result may be repeated at the Investigator's discretion).
15. Participant with negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg)) and hepatitis C virus antibody (HCV Ab) test results at Screening.
16. No clinically significant abnormalities in 12-lead electrocardiogram (ECG) or vital signs determined within 28 days before first dose of IMP.
17. Participant must be available to complete the study (including all follow up visits).
18. Participant must be willing to consent to have data entered into The Over Volunteering Prevention System (TOPS).
19. Participant must provide written informed consent to participate in the study.

To be re-confirmed on Day 0 / prior to each dosing visit

2. Participant with a negative urinary drugs of abuse screen (including alcohol and cotinine) prior to dosing unless there is a documented medical explanation for the positive result other than drugs of abuse (e.g., the participant has been prescribed opioids for pain). (N.B.: A positive test result may be repeated at the Investigator's discretion).
3. Female participant of childbearing potential or non-childbearing potential with a negative pregnancy test on admission.

Exclusion Criteria

To be confirmed at Screening:

1. Participant with any clinically significant medical (cardiovascular disease, pulmonary, hepatic, gallbladder or biliary tract, renal, haematological, gastrointestinal, endocrine, immunologic, dermatological, neurological, autoimmune disease or current infection) or psychiatric condition (see also exclusion criterion number 21) that, in the opinion of the Investigator, precludes participation in the study. This will include any clinically significant abnormal serum biochemistry results and/or haematological results and/or urine analytical results.
2. Participant with a history of heart disease or of rheumatic fever.
3. Participant with a significant acute febrile illness (including fever of 38.0\^0C or greater within 14 days) of each dose of IMP (Days 0, 21 and 42).
4. Participant who has chronic diseases: Chronic diseases will include all autoimmune and immunocompromising conditions and any other chronic condition, which at the judgment of the Investigator, may put the participant at higher risk of side effects from the study vaccine. Conditions in the latter category might include unexplained anaemia, hepato-biliary disease, uncontrolled hypertension, participant with prosthetic joints or heart valves, etc.
5. Participant with sickle cell anaemia.
6. Participant who has undertaken a course of antibiotics/antibacterials within 28 days prior to each dose of IMP (Days 0, 21 and 42).
7. Use of prescription or non-prescription drugs within 28 days or 5 half-lives (whichever is longer) prior to receiving the first dose of IMP, unless in the opinion of the Investigator and Sponsor's Responsible Physician the medication will not interfere with the study procedures or compromise participant safety.
8. Participant who uses antacids, proton pump inhibitors or H2 blockers on a regular basis or has consumed proton pump inhibitors or H2 blockers within 24 hours prior to each dose of IMP.
9. Participant who has received investigational or licensed vaccines in the 28 days prior to dosing or anticipates receiving a vaccine other than study medication up to Day 84 of the study.
10. Participant with symptoms consistent with Typhoid fever concurrent with travel to countries where typhoid infection is endemic (most of the developing world) within 2 years prior to first dose of IMP.
11. Vaccination against Typhoid within 3 years prior to first dose of IMP.
12. Ingestion of Typhoid bacteria in a challenge study within 3 years prior to dosing.
13. Participant who works as a commercial food handler.
14. Participant who is a health care worker in direct contact with patients.
15. Participant who is a childcare worker.
16. Participant who has household contact with immuno-compromised individuals, pregnant women, children \< 2 years of age or individuals \> 70 years of age.
17. Participant who has person(s) living with him/her who, in the opinion of the Investigator, may be at risk of disease if exposed to the vaccine strain.
18. Participant with a known impairment of immune function or receiving (or has received in the 6 months prior to study entry) cytotoxic drugs or immunosuppressive therapy (including systemic corticosteroids).
19. Participant who is a current smoker (cigarettes, tobacco and/or e-cigarettes) or has stopped smoking in the last 3 months prior to Screening.
20. A clinically significant history of drug or alcohol abuse \[defined as the consumption of more than 14 units of alcohol a week\] within the past two years prior to Screening.
21. Inability to communicate well with the Investigators (i.e., language problem, poor mental development or impaired cerebral function).
22. Participation in a New Chemical Entity (NCE) clinical study within the previous 3 months or a marketed drug clinical study within the 30 days before the first dose of IMP. (Washout period between studies is defined as the period of time elapsed between receiving the last dose of the previous study and receiving the first dose of the next study).
23. Donation of 450 millilitres (mL) or more blood within the 3 months before the first dose of IMP.
24. Participant who, in the opinion of the Investigator, is unsuitable for participation in the study.

To be re-confirmed at Day 0 / prior to each dosing visit:

2. Use of prescription or non-prescription drugs since Screening, unless in the opinion of the Investigator and Sponsor's Responsible Physician, the medication will not interfere with the study procedures or compromise participant safety.
3. Participation in a clinical study since Screening.
4. Donation of 450 mL or more blood since Screening.
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Simbec Research

INDUSTRY

Sponsor Role collaborator

Prokarium Ltd

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Simbec Research

Merthyr Tydfil, Wales, United Kingdom

Site Status

Countries

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United Kingdom

References

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Soulier A, Prevosto C, Chol M, Deban L, Cranenburgh RM. Engineering a Novel Bivalent Oral Vaccine against Enteric Fever. Int J Mol Sci. 2021 Mar 23;22(6):3287. doi: 10.3390/ijms22063287.

Reference Type DERIVED
PMID: 33807097 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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PRK-ENT-001

Identifier Type: -

Identifier Source: org_study_id

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