Typhoid Fever
Conditions
Keywords
Typhoid fever, Glycoconjugate vaccine, Vi polysaccharide, Immunogenicity
Brief summary
The purpose of this study is to evaluate the immunogenicity and the kinetics of the anti-Vi antibody response following secondary vaccination with the Novartis Vaccines Institute for Global Health (NVGH) Vi-CRM197 vaccine in healthy adults previously vaccinated with either the NVGH Vi-CRM197 or Vi-polysaccharide (Typherix) in the H01\_04TP study (NCT01193907) and the immunogenicity and the kinetics of the anti-Vi antibody response following primary vaccination with the NVGH Vi-CRM197 vaccine in naïve healthy adults.
Interventions
BIOLOGICALNVGH Vi-CRM197
Vi-CRM197 glycoconjugated vaccine
Sponsors
Novartis
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 42 Years
Healthy volunteers
Yes
Inclusion criteria
All Subjects: 1. Males and females of age ≥18 to ≤42 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. 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. H01\_04TP subjects only: 5. Individuals who previously participated in the H01\_04TP study and were vaccinated with either NVGH Vi-CRM197 (5μg) or with the licensed Vi-PS. 6. Individuals who have received no Vi vaccination subsequent to the one received in the H01\_04TP study. Inclusion criteria All subjects: 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, 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 received any 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 12. Individuals who have received blood, blood products and/or plasma derivatives including parenteral immunoglobulin preparations in the past 12 weeks. 13. Individuals who are part of study personnel or close family members to the personnel conducting this study. 14. Individuals with body temperature \> 38.0 degrees Celsius within 3 days of intended study immunization. 15. BMI \> 35 kg/m2. 16. Individuals with history of substance or alcohol abuse within the past 2 years. 17. 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. 18. Females with history of stillbirth, neonatal loss, or previous infant with anomaly. 19. Individuals who have a previously ascertained or suspected disease caused by S. Typhi. 20. Individuals who have had household contact with/and or intimate exposure to an individual with laboratory confirmed S. Typhi. 21. Any condition which, in the opinion of the investigator may interfere with the evaluation of the study objectives. Naïve subjects only: 22. Individuals who have previously received any vaccine against typhoid fever (either oral live attenuated or injectable vaccines)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti-Vi ELISA Geometric Mean Concentration (GMC) | At 3 days after vaccination | To evaluate the immunogenicity and the kinetics of the immune response induced by one dose of NVGH Vi-CRM197 at study day 3 after vaccination as as measured by enzyme-linked immunosorbent assay (ELISA) |
| Anti-Vi ELISA GMC | At 7 days after vaccination | To evaluate the immunogenicity and the kinetics of the immune response induced by one dose of NVGH Vi-CRM197 at study day 7 after vaccination as as measured by ELISA |
| Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titers | At 3 days after vaccination as compared to baseline | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Any (Local, Systemic and Other) Post Vaccination Reaction | 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, fatigue and fever. |
| Number of Subjects Reporting AE | During the 28-day period after vaccination | AE during 28 days after vaccination(including solicited reactions during 7 days after vaccination) |
| Number of Subjects Reporting Serious Adverse Events (SAEs) | During the 28-day period after vaccination | — |
Countries
Belgium
Participant flow
Recruitment details
First subject enrolled: 17 OCT 11, Last subject completed: 13 DEC 11.
Participants by arm
| Arm | Count |
|---|---|
| NVGH Vi-CRM/NVGH Vi-CRM One 0.5 mL dose of NVGH Vi-CRM197 5.0 mcg in adults who received 1 dose of NVGH Vi-CRM197 5.0 mcg in H01\_04TP study | 18 |
| Vi-PS/NVGH Vi-CRM One 0.5 mL dose of NVGH Vi-CRM197 5.0 mcg in adults who received 1 dose of Vi-polysaccharide (PS) in H01\_04TP study | 13 |
| NVGH Vi-CRM One 0.5 mL dose of NVGH Vi-CRM197 5.0 mcg in naive adults | 20 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Not meeting Inclusion Criteria | 4 | 1 | 0 |
Baseline characteristics
| Characteristic | Vi-PS/NVGH Vi-CRM | NVGH Vi-CRM | NVGH Vi-CRM/NVGH Vi-CRM | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 20 Participants | 18 Participants | 51 Participants |
| Age, Continuous | 26.3 years STANDARD_DEVIATION 6.6 | 26.0 years STANDARD_DEVIATION 6.2 | 25.3 years STANDARD_DEVIATION 5.8 | 25.8 years STANDARD_DEVIATION 6 |
| Region of Enrollment Belgium | 13 participants | 20 participants | 18 participants | 51 participants |
| Sex: Female, Male Female | 2 Participants | 10 Participants | 5 Participants | 17 Participants |
| Sex: Female, Male Male | 11 Participants | 10 Participants | 13 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 14 | 12 / 12 | 20 / 20 |
| serious Total, serious adverse events | 0 / 14 | 0 / 12 | 0 / 20 |
Outcome results
Primary
Anti-Vi ELISA Geometric Mean Concentration (GMC)
To evaluate the immunogenicity and the kinetics of the immune response induced by one dose of NVGH Vi-CRM197 at study day 3 after vaccination as as measured by enzyme-linked immunosorbent assay (ELISA)
Time frame: At 3 days after vaccination
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| NVGH Vi-CRM/NVGH Vi-CRM | Anti-Vi ELISA Geometric Mean Concentration (GMC) | 35 ELISA Units/mL |
| Vi-PS/NVGH Vi-CRM | Anti-Vi ELISA Geometric Mean Concentration (GMC) | 31 ELISA Units/mL |
| NVGH Vi-CRM | Anti-Vi ELISA Geometric Mean Concentration (GMC) | 3.22 ELISA Units/mL |
Primary
Anti-Vi ELISA GMC
To evaluate the immunogenicity and the kinetics of the immune response induced by one dose of NVGH Vi-CRM197 at study day 7 after vaccination as as measured by ELISA
Time frame: At 7 days after vaccination
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| NVGH Vi-CRM/NVGH Vi-CRM | Anti-Vi ELISA GMC | 65 ELISA Units/mL |
| Vi-PS/NVGH Vi-CRM | Anti-Vi ELISA GMC | 40 ELISA Units/mL |
| NVGH Vi-CRM | Anti-Vi ELISA GMC | 20 ELISA Units/mL |
Primary
Anti-Vi ELISA GMC
To evaluate the immunogenicity and the kinetics of the immune response induced by one dose of NVGH Vi-CRM197 at study day 28 after vaccination as as measured by ELISA
Time frame: At 28 days after vaccination
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| NVGH Vi-CRM/NVGH Vi-CRM | Anti-Vi ELISA GMC | 44 ELISA Units/mL |
| Vi-PS/NVGH Vi-CRM | Anti-Vi ELISA GMC | 50 ELISA Units/mL |
| NVGH Vi-CRM | Anti-Vi ELISA GMC | 111 ELISA Units/mL |
Primary
Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titers
Time frame: At 7 days after vaccination as compared to baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVGH Vi-CRM/NVGH Vi-CRM | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titers | 7 percentage of subjects |
| Vi-PS/NVGH Vi-CRM | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titers | 0 percentage of subjects |
| NVGH Vi-CRM | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titers | 60 percentage of subjects |
Primary
Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titers
Time frame: At 3 days after vaccination as compared to baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVGH Vi-CRM/NVGH Vi-CRM | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titers | 0 percentage of subjects |
| Vi-PS/NVGH Vi-CRM | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titers | 0 percentage of subjects |
| NVGH Vi-CRM | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titers | 0 percentage of subjects |
Primary
Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titers
Time frame: At 28 days after vaccination as compared to baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVGH Vi-CRM/NVGH Vi-CRM | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titers | 0 percentage of subjects |
| Vi-PS/NVGH Vi-CRM | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titers | 17 percentage of subjects |
| NVGH Vi-CRM | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titers | 100 percentage of subjects |
Secondary
Number of Subjects Reporting AE
AE during 28 days after vaccination(including solicited reactions during 7 days after vaccination)
Time frame: During the 28-day period after vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVGH Vi-CRM/NVGH Vi-CRM | Number of Subjects Reporting AE | 14 participants |
| Vi-PS/NVGH Vi-CRM | Number of Subjects Reporting AE | 12 participants |
| NVGH Vi-CRM | Number of Subjects Reporting AE | 20 participants |
Secondary
Number of Subjects Reporting Any (Local, Systemic and Other) Post Vaccination Reaction
Solicited reactions collected during the 7-day period after vaccination are pain, erythema, induration, chills, malaise, myalgia, headache, arthralgia, fatigue and fever.
Time frame: During the 7-day period after vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVGH Vi-CRM/NVGH Vi-CRM | Number of Subjects Reporting Any (Local, Systemic and Other) Post Vaccination Reaction | 14 participants |
| Vi-PS/NVGH Vi-CRM | Number of Subjects Reporting Any (Local, Systemic and Other) Post Vaccination Reaction | 12 participants |
| NVGH Vi-CRM | Number of Subjects Reporting Any (Local, Systemic and Other) Post Vaccination Reaction | 18 participants |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs)
Time frame: During the 28-day period after vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVGH Vi-CRM/NVGH Vi-CRM | Number of Subjects Reporting Serious Adverse Events (SAEs) | 0 participants |
| Vi-PS/NVGH Vi-CRM | Number of Subjects Reporting Serious Adverse Events (SAEs) | 0 participants |
| NVGH Vi-CRM | Number of Subjects Reporting Serious Adverse Events (SAEs) | 0 participants |