E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active immunisation for the prevention of typhoid infection in healthy adults. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10045275 |
E.1.2 | Term | Typhoid fever |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045272 |
E.1.2 | Term | Typhoid |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Using an established model of human typhoid infection, whereby healthy adults are deliberately infected with typhoid-causing bacteria, we will determine how effective a new oral typhoid vaccine (M01ZH09) is in preventing infection. A previously licensed oral typhoid vaccine (Ty21a) will be used to make sure the challenge model used works properly. |
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E.2.2 | Secondary objectives of the trial |
1) To compare the clinical and laboratory features of the response to typhoid infection in participants who have previously been vaccinated with M01ZH09, vaccine-placebo or Ty21a. These features will include the course of the illness, the point at which participants may develop typhoid bloodstream infection, and the level of inflammation produced in response to infection. 2) To compare the response of the immune systems to typhoid infection in participants who have previously been vaccinated with M01ZH09, vaccine-placebo or Ty21a. 3)To assess the safety and side-effects of the novel vaccine (M01ZH09) and to compare these with the other two groups (those receiving vaccine-placebo and those receiving the Ty21a vaccine). 4) To develop new methods for diagnosing typhoid infection, which are currently poor. 5) To explore how the genetic response (which protein encoding-genes within the participants DNA are switched on and off) to vaccination in the three groups varies. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participant is willing and able to give informed consent for participation after the nature of the study has been explained. 2. Male or female, aged 18-60 years inclusive. 3. In good health as determined by medical history, history-directed physical examination and the clinical judgment of the investigators. 4. Female participants of child bearing potential must be willing to ensure that they or their partner use effective contraception for one month prior to challenge and continue to do so until a negative stool sample has been obtained at least 3 months after completion of antibiotic treatment. 5. Able and willing (in the Investigator’s opinion) to comply with all study requirements, including the capacity for good personal hygiene. 6. Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study. 7. Willing to allow the Health Protection Unit to be informed of participation in the study. 8. For those involved in provision of health or social care to vulnerable groups only – willing to allow his or her employer to be notified of participation in the study. 9. Willing to give his or her contacts (defined as someone who is likely to have been exposed to the excreta of a challenged participant, usually a household or sexual contact) letters informing them of the participants involvement in the study and offering the contact screening for Salmonella Typhi carriage. 10. Agree to refrain from future blood donation. 11. Be willing to have 24-hr contact with study staff during the four weeks post-challenge. |
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E.4 | Principal exclusion criteria |
1. Are unwilling or unable to give written informed consent to participate in the study. 2. Have previously received any typhoid vaccine or been diagnosed with laboratory confirmed typhoid. 4. Have known/suspected autoimmune disease or impairment/alteration of immune function resulting from (for example): a) Congenital or acquired immunodeficiency (including IgA deficiency) b) Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months or long-term systemic corticosteroid therapy. c) HIV infection. 5. History of significant cardiovascular disease, respiratory disease, endocrine disorder, renal or bladder disease, biliary tract disease, gastrointestinal disease (including hepatitis B or C), neurological disease, metabolic disease, haematological diagnosis, psychiatric illness (requiring hospitalisation), current known or suspected drug abuse or alcohol abuse, history of moderate or severe depression or anxiety, infectious disease, cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). 6. Have implants or prostheses in situ. 7. Have any clinically significant abnormal finding on biochemistry or haematology blood tests or urine analysis. 8. Contra-indication to taking ciprofloxacin, β-lactam antibiotics, or trimethoprim/sulfamethoxazole. 9. Female participant who is pregnant, lactating or who is unwilling to ensure that they or their partner use effective contraception for one month prior to challenge and continue to do so until a negative stool sample, a minimum of 3 months after completion of antibiotic treatment, has been obtained. 10. Current occupation involving clinical or social work involving direct contact with: a)young children (those attending pre-school groups, nursery or under the age of 2 years) b)highly susceptible patients or persons in whom typhoid infectious would have particularly serious consequences, including the elderly (unless willing not to work until demonstrated to not be infected with Salmonella Typhi in accordance with guidance from the Health Protection Agency). 11. Current occupation as a commercial food handler (involving preparing or serving unwrapped foods not subjected to further heating). 12. Household contact under 2 years of age or who is immunocompromised by treatment or disease. 13. Have elective surgery or other procedures requiring general anaesthesia scheduled during the vaccine/challenge period, at time of enrollment. 14. Have participated in another research study involving an IMP that might affect risk of typhoid infection or compromise the integrity of the study within the 30 days prior to enrolment (e.g. significant volumes of blood already taken in previous study) as assessed by both participant questioning and the TOPS Over Volunteering Prevention System database. 15. Have donated blood in the preceeding 3 months (temporary exclusion only). 16. Have received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 3 months. 17. Have any other significant disease or disorder which, in the opinion of the investigators, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant’s ability to participate in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine the relative protective effect of M01ZH09 vaccine compared to placebo using a healthy adult typhoid challenge model, with Ty21a vaccine as a positive control. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end trial will be when the last assay has been completed on the last cellular participant sample. This has been chosen as some assays may be performed in North America and there may be delays due to transportation problems etc. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |