Typhoid Fever
Conditions
Keywords
Typhoid fever, Glycoconjugate vaccine, Vi polysaccharide, Immunogenicity
Brief summary
This trial is aimed to evaluate the safety and immunogenicity profiles of three formulations of Vi-CRM197 conjugate vaccine against S. Typhi in healthy human adults in comparison with the currently licensed Vi polysaccharide vaccine
Interventions
BIOLOGICALNVGH Vi-CRM197 12.5 mcg
1 dose of 0.5 mL
BIOLOGICALNVGH Vi-CRM197 5.0 mcg
1 dose of 0.5 mL
BIOLOGICALNVGH Vi-CRM197 1.25 mcg
1 dose of 0.5 mL
BIOLOGICALVi-polysaccharide vaccine
1 dose of 0.5 mL containing 25 mcg of Vi polysaccharide
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
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 urine screening tests for drug addition (Opiate, Cocaine, Amph/Metamphetamine, 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.
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Any Post Immunization Reactions | During the 7-day period after vaccination | Solicited reactions collected during the 7-day period after vaccination are pain, erythema, induration, chills, malaise, myalgia, headache, arthralgia and fatigue |
| Number of Subjects Reporting Adverse Events | During the 28-day period after vaccination | — |
| Anti-Vi ELISA (Enzyme Linked Immunosorbent Assay) Geometric Mean Concentration (GMC) | At 28 days after vaccination | — |
| Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer | At 28 days after vaccination | — |
Countries
Belgium
Participant flow
Recruitment details
Date of first enrollment: 04 OCT 10 Date of last visit: 18 NOV 10
Participants by arm
| Arm | Count |
|---|---|
| NVGH Vi-CRM197 12.5 Mcg 1 dose of 0.5 mL containing 12.5 mcg of Vi-CRM | 22 |
| NVGH Vi-CRM197 5.0 Mcg 1 dose of 0.5 mL containing 5.0 mcg of Vi-CRM | 22 |
| NVGH Vi-CRM197 1.25 Mcg 1 dose of 0.5 mL containing 1.25 mcg of Vi-CRM | 22 |
| Typherix 1 dose of 0.5 mL containing 25 mcg of Vi-PS | 22 |
| Total | 88 |
Baseline characteristics
| Characteristic | NVGH Vi-CRM197 5.0 Mcg | NVGH Vi-CRM197 1.25 Mcg | NVGH Vi-CRM197 12.5 Mcg | Typherix | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 22 Participants | 22 Participants | 22 Participants | 88 Participants |
| Age, Continuous | 24.3 years STANDARD_DEVIATION 5.4 | 24.0 years STANDARD_DEVIATION 5.7 | 24.3 years STANDARD_DEVIATION 4.9 | 23.8 years STANDARD_DEVIATION 5.5 | 24.1 years STANDARD_DEVIATION 5.3 |
| Region of Enrollment Belgium | 22 participants | 22 participants | 22 participants | 22 participants | 88 participants |
| Sex: Female, Male Female | 15 Participants | 17 Participants | 14 Participants | 15 Participants | 61 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 8 Participants | 7 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 21 | 19 / 22 | 22 / 22 | 19 / 22 |
| serious Total, serious adverse events | 0 / 21 | 0 / 22 | 0 / 22 | 0 / 22 |
Outcome results
Primary
Anti-Vi ELISA (Enzyme Linked Immunosorbent Assay) Geometric Mean Concentration (GMC)
Time frame: At 28 days after vaccination
| Arm | Measure | Value (MEAN) |
|---|---|---|
| NVGH Vi-CRM197 12.5 Mcg | Anti-Vi ELISA (Enzyme Linked Immunosorbent Assay) Geometric Mean Concentration (GMC) | 192 GMC |
| NVGH Vi-CRM197 5.0 Mcg | Anti-Vi ELISA (Enzyme Linked Immunosorbent Assay) Geometric Mean Concentration (GMC) | 111 GMC |
| NVGH Vi-CRM197 1.25 Mcg | Anti-Vi ELISA (Enzyme Linked Immunosorbent Assay) Geometric Mean Concentration (GMC) | 63 GMC |
| Typherix | Anti-Vi ELISA (Enzyme Linked Immunosorbent Assay) Geometric Mean Concentration (GMC) | 37 GMC |
Primary
Number of Subjects Reporting Adverse Events
Time frame: During the 28-day period after vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVGH Vi-CRM197 12.5 Mcg | Number of Subjects Reporting Adverse Events | 11 participants |
| NVGH Vi-CRM197 5.0 Mcg | Number of Subjects Reporting Adverse Events | 16 participants |
| NVGH Vi-CRM197 1.25 Mcg | Number of Subjects Reporting Adverse Events | 18 participants |
| Typherix | Number of Subjects Reporting Adverse Events | 15 participants |
Primary
Number of Subjects Reporting Any Post Immunization Reactions
Solicited reactions collected during the 7-day period after vaccination are pain, erythema, induration, chills, malaise, myalgia, headache, arthralgia and fatigue
Time frame: During the 7-day period after vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVGH Vi-CRM197 12.5 Mcg | Number of Subjects Reporting Any Post Immunization Reactions | 18 participants |
| NVGH Vi-CRM197 5.0 Mcg | Number of Subjects Reporting Any Post Immunization Reactions | 19 participants |
| NVGH Vi-CRM197 1.25 Mcg | Number of Subjects Reporting Any Post Immunization Reactions | 22 participants |
| Typherix | Number of Subjects Reporting Any Post Immunization Reactions | 16 participants |
Primary
Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer
Time frame: At 28 days after vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVGH Vi-CRM197 12.5 Mcg | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer | 100 percentage of subjects |
| NVGH Vi-CRM197 5.0 Mcg | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer | 100 percentage of subjects |
| NVGH Vi-CRM197 1.25 Mcg | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer | 95 percentage of subjects |
| Typherix | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer | 95 percentage of subjects |