E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Salmonella enterica serovar Typhi (S. Typhi) disease |
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MedDRA Classification |
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 |
The goal is to evaluate the safety profile of three different dose levels of Vi-CRM197 in adults compared to that of the licensed Vi polysaccharide vaccine (Typherix, GSK), by measuring rates of post immunization reactions and adverse events. The goal is also to evaluate the immunogenicity profile of three different dose levels of Vi-CRM197 in adults compared to that of the licensed Vi polysaccharide vaccine (Typherix, GSK), by measuring enzyme-linked immunosorbent assay (ELISA), at 28 days post-immunization.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males and females of age ≥18 to ≤40 years. 2. Individuals who, after the nature of the study have been explained to them, have given written consent according to local regulatory requirements. 3. Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator. 4. Individuals with negative screening tests for drug addition as follows: opiate, cocaine, amphetamine/metamphetamine and cannabinoides. 5. If women, use of birth control one month before study start, a negative pregnancy test and willingness to use birth control measures for the entire study duration. |
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E.4 | Principal exclusion criteria |
1. Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study. 2. Individuals with any progressive or severe neurological disorder, seizure disorder or Guillain-Barré syndrome. 3. Individuals who are not able to understand and to follow all required study procedures for the whole period of the study. 4. Individuals with history of any illness that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study. 5. Individuals with known or suspected HIV infection or HIV related disease, with history of an autoimmune disorder or any other known or suspected impairment /alteration of the immune system, or under immunosuppressive therapy including use of systemic corticosteroids or chronic use of inhaled high-potency corticosteroids within the previous 30 days, or were in chemotherapy treatment within the past 6 months. 6. Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. 7. Individuals with any serious chronic or progressive disease according to judgment of the investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease). 8. Individuals who have any malignancy or lymphoproliferative disorder. 9. Individuals with history of allergy to vaccine components. 10. Individuals participating in any clinical trial with another investigational product 30 days prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study. 11. Individuals who have previously received any vaccines against typhoid fever (either oral live attenuated or injectable vaccines) 12. Individuals who received any other vaccines within 4 weeks prior to enrolment in this study or who are planning to receive any vaccine within 4 weeks from the study vaccine 13. Individuals who have received blood, blood products and/or plasma derivatives including parenteral immunoglobulin preparations in the past 12 weeks. 14. Individuals who are part of study personnel or close family members to the personnel conducting this study. 15. Individuals with body temperature > 38.0 degrees Celsius within 3 days of intended study immunization. 16. BMI > 35 kg/m2. 17. Individuals with history of substance or alcohol abuse within the past 2 years. 18. Women who are pregnant or breast-feeding or of childbearing age who have not used any birth control measure one month prior to study start or do not plan to use acceptable birth control measures, for the duration of the study. 19. Females with history of stillbirth, neonatal loss, or previous infant with anomaly. 20. Individuals who have a previously ascertained or suspected disease caused by S. Typhi. 21. Individuals who have had household contact with/and or intimate exposure to an individual with laboratory confirmed S. Typhi. 22. Any condition which, in the opinion of the investigator may interfere with the evaluation of the study objectives.
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E.5 End points |
E.5.1 | Primary end point(s) |
Immunogenicity Endpoints The measures of immunogenicity, against the Vi antigen of S. Typhi, will include: - Geometric mean concentrations (GMCs), pre- and post-vaccination, as determined by ELISA, and applicable geometric mean ratios between post- and pre-vaccination samples. - Seroconversion rate: percentage of subjects achieving at least a four-fold rise in ELISA antibody concentration in the post-vaccination blood sample
Safety Endpoints (criteria for assessing safety endpoints) The measures of safety will include: - Numbers and percentage of subjects with solicited local and systemic adverse reactions as well as numbers and percentage of subjects with reported unsolicited adverse events and serious adverse events. Solicited local reactions include erythema, induration and pain at injection site; solicited systemic reactions include headache, arthralgia, chills, fatigue, malaise, myalgia, and fever as measured by axillary temperature for Day 1 through 7 of the study. All local and systemic reactions will be collected for 7 days after immunization (i.e., days 1 to 7). All AEs will be collected throughout the study duration (28 days).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
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 | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 trail ends when the last subject last visit has been performed |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
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 |