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

NCT04349553 | Completed Phase 1 Results

• 1 other identifier: PRK-ENT-001
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Enteric Fever

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment Emergent Adverse Events

  Number of adverse events as assessed by adverse events, laboratory safety tests (biochemistry, haematology, urinalysis), vital signs and physical examination.

  From Day 0 to Day 84

• Number of Participants With Abnormal Clinically or Non-clinically Significant or Out of Expected Range Tests

  Tests include blood pressure, heart rate, physical examination, laboratory biochemistry, haematology and urinalysis tests

  From Day 0 to Day 84

Secondary Outcomes (6)

• Number of Participants With Serious Adverse Events

  From Day 85 to Day 224

• Number of Participants With Abnormal Clinically or Non-clinically Significant or Out of Expected Range Tests

  From Day 85 to Day 224

• Fold-Increase Serum IgG Antibody Concentration of Specific Serum Immunoglobulin (Ig)G Antibodies to the Antigen H:a

  Day 0, Day 21, Day 42, and Day 84

• Fold-Increase Serum IgG Antibody Concentration of Specific Serum Immunoglobulin (Ig)G Antibodies to the Antigen H:d

  Day 0, Day 21, Day 42, and Day 84

• Fold-Increase Serum IgG Antibody Concentration of Specific Serum Immunoglobulin (Ig)G Antibodies to the Antigen LPSO:2

  Day 0, Day 21, Day 42, and Day 84

Study Arms (4)

ZH9PA 1x10^9 CFU

EXPERIMENTAL

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

Biological: Placebo; Biological: ZH9PA

ZH9PA 1x10^10 CFU

EXPERIMENTAL

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

Biological: Placebo; Biological: ZH9PA

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

EXPERIMENTAL

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

Biological: ZH9PA and ZH9; Biological: Placebo

Placebo

PLACEBO COMPARATOR

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

Biological: ZH9PA and ZH9; Biological: Placebo; Biological: ZH9PA

Interventions

ZH9PA and ZH9 BIOLOGICAL

150mL vaccine for oral administration

Also known as: Entervax

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

Placebo BIOLOGICAL

150mL vaccine for oral administration

Placebo; ZH9PA 1x10^10 CFU; ZH9PA 1x10^10 CFU plus ZH9 1x10^10 CFU; ZH9PA 1x10^9 CFU

ZH9PA BIOLOGICAL

150mL vaccine for oral administration

Placebo; ZH9PA 1x10^10 CFU; ZH9PA 1x10^9 CFU

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• To be confirmed at Screening
• Healthy male and female participants 18 to 45 years of age, inclusive.
• 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).
• 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).
• Female participant of childbearing potential or non-childbearing potential with a negative pregnancy test at Screening.
• 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.
• 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.
• Participant with a body mass index (BMI) of ≥ 19 or ≤34 kg/m\^2 (BMI = body weight (kg) / \[height (m)\]\^2).
• No clinically significant history of liver or active gall bladder disease.
• No clinically significant history of ongoing gastro-intestinal disease or abnormality.
• No clinically significant history of previous allergy / sensitivity to ZH9/ZH9PA or sodium bicarbonate.
• No clinically significant history of anaphylactic shock following vaccination.
• No clinically significant history of hypersensitivity (e.g., hives/rash/swollen lips/difficulty with breathing) to azithromycin, ampicillin, trimethoprim-sulfamethoxazole or ciprofloxacin.
• 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.
• 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).

You may not qualify if:

• To be confirmed at Screening:
• Participant with a history of heart disease or of rheumatic fever.
• 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).
• 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.
• Participant with sickle cell anaemia.
• Participant who has undertaken a course of antibiotics/antibacterials within 28 days prior to each dose of IMP (Days 0, 21 and 42).
• 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.
• 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.
• 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.
• 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.
• Vaccination against Typhoid within 3 years prior to first dose of IMP.
• Ingestion of Typhoid bacteria in a challenge study within 3 years prior to dosing.
• Participant who works as a commercial food handler.
• Participant who is a health care worker in direct contact with patients.
• Participant who is a childcare worker.

Sponsors & Collaborators

• Prokarium Ltd: lead
• Simbec Research: collaborator

Study Sites (1)

Simbec Research

Merthyr Tydfil, Wales, CF48 4DR, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33807097 DERIVED

MeSH Terms

Conditions

Typhoid Fever

Condition Hierarchy (Ancestors)

Salmonella Infections; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Kristen Albright
• Organization: Prokarium

kristen.albright@prokarium.com

+44 (0) 7375 124 275

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Placebo
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: January 11, 2020
• First Posted: April 16, 2020
• Study Start: December 16, 2019
• Primary Completion: September 28, 2020
• Study Completion: February 15, 2021
• Last Updated: August 17, 2025
• Results First Posted: August 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)