Typhoid Fever
Conditions
Brief summary
This phase 2 trial is aimed to obtain information on the safety and immunogenicity of the Vi-CRM197 in subjects from various age groups in India and Pakistan where Typhoid Fever is highly endemic and an efficacious vaccine against this disease is very much needed.
Interventions
BIOLOGICALVi-CRM197 vaccine
BIOLOGICALVi Polysaccharide (PS) vaccine
BIOLOGICALPneumococcal conjugate vaccine
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Main eligibility criteria: * Subjects belonging to 4 age groups will be enrolled into the trial: adults (18 to 45 years of age), children (24 to 59 months of age), older infants (9 to 12 months of age at enrollment) and infants (6 weeks of age at enrolment). * Written informed consent will be obtained by the all subjects or their parents/ guardians (depending on the age group) before enrollment into the trial. * Only females with a negative pregnancy test and willing to participate in family planning consultations (organized by the site study team) will be allowed to participate to the trial. * Infants who have been vaccinated with 1 dose of BCG, HBV and OPV at birth can be enrolled into the trial, while infants who have received DTwP+HBV+Hib or OPV due at 6 weeks of age as per local EPI schedule cannot be enrolled into the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Subjects With at Least 4-fold Increase in Anti-Vi Enzyme-linked Immunosorbent Assay (ELISA) Titer | At 28 days after last vaccination as compared to baseline |
| Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer | At 6 months after last vaccination as compared to baseline |
| Anti-Vi ELISA Geometric Mean Concentration (GMC) | At 28 days after last vaccination |
| Anti-Vi ELISA GMC | At 6 months after last vaccination |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Solicited Local and Systemic Reaction, After Any Vaccination | During the 7-day follow-up period after vaccination | Solicited local reactions were: Adults, children, older infants, infants: erythema, induration and pain/tenderness at the injection site. Solicited systemic reactions were: Adults: chills, malaise, myalgia, arthralgia, headache, fatigue, rash and fever. Children, older infants and infants: lethargy, irritability, vomiting, diarrhoea, loss of appetite, rash and fever (and persistent crying in infants). |
Countries
India, Pakistan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vi-CRM, Adults Adults (18 to 45 years) receiving 1 dose of NVGH Vi-CRM197 vaccine | 40 |
| Vi-PS, Adults Adults (18 to 45 years) receiving 1 dose of licensed Vi Polysaccharide vaccine | 40 |
| Vi-CRM, Children Children (24 to 59 months) receiving 2 doses of NVGH Vi-CRM197 vaccine | 20 |
| Vi-PS, Children Children (24 to 59 months) receiving 1 dose of licensed Vi Polysaccharide vaccine and 1 dose of Pneumococcal conjugate vaccine | 20 |
| Vi-CRM, Older Infants Older Infants (9 to 12 months) receiving 2 doses of NVGH Vi-CRM197 vaccine | 20 |
| PNC13, Older Infants Older Infants (9 to 12 months) receiving 2 doses of Pneumococcal conjugate vaccine | 20 |
| Vi-CRM, Infants Infants (6 to 8 weeks) receiving 3 doses of NVGH Vi-CRM197 vaccine | 20 |
| PNC13, Infants Infants (6 to 8 weeks) receiving 3 doses of Pneumococcal conjugate vaccine | 20 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 3 | 0 | 0 | 1 | 1 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Vi-CRM, Adults | Vi-PS, Adults | Vi-CRM, Children | Vi-PS, Children | Vi-CRM, Older Infants | PNC13, Older Infants | Vi-CRM, Infants | PNC13, Infants | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18 years to 45 years (adults) | 40 participants | 40 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 80 participants |
| Age, Customized 24 months 59 months (children) | 0 participants | 0 participants | 20 participants | 20 participants | 0 participants | 0 participants | 0 participants | 0 participants | 40 participants |
| Age, Customized 6 weeks to 8 weeks (infants) | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 20 participants | 20 participants | 40 participants |
| Age, Customized 9 months to 12 months (older infants) | 0 participants | 0 participants | 0 participants | 0 participants | 20 participants | 20 participants | 0 participants | 0 participants | 40 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 40 Participants | 40 Participants | 20 Participants | 20 Participants | 20 Participants | 20 Participants | 20 Participants | 20 Participants | 200 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment India | 20 participants | 20 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 40 participants |
| Region of Enrollment Pakistan | 20 participants | 20 participants | 20 participants | 20 participants | 20 participants | 20 participants | 20 participants | 20 participants | 160 participants |
| Sex: Female, Male Female | 18 Participants | 17 Participants | 11 Participants | 9 Participants | 12 Participants | 12 Participants | 10 Participants | 8 Participants | 97 Participants |
| Sex: Female, Male Male | 22 Participants | 23 Participants | 9 Participants | 11 Participants | 8 Participants | 8 Participants | 10 Participants | 12 Participants | 103 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 24 / 40 | 29 / 40 | 19 / 20 | 17 / 20 | 18 / 20 | 20 / 20 | 20 / 20 | 19 / 19 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 | 2 / 20 | 1 / 20 | 4 / 20 | 5 / 20 | 5 / 20 | 3 / 19 |
Outcome results
Primary
Anti-Vi ELISA Geometric Mean Concentration (GMC)
Time frame: At 28 days after last vaccination
Population: Intention-to-treat analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Vi-CRM, Adults | Anti-Vi ELISA Geometric Mean Concentration (GMC) | 153 ELISA Units/mL |
| Vi-PS, Adults | Anti-Vi ELISA Geometric Mean Concentration (GMC) | 44 ELISA Units/mL |
| Vi-CRM, Children | Anti-Vi ELISA Geometric Mean Concentration (GMC) | 136 ELISA Units/mL |
| Vi-PS, Children | Anti-Vi ELISA Geometric Mean Concentration (GMC) | 53 ELISA Units/mL |
| Vi-CRM, Older Infants | Anti-Vi ELISA Geometric Mean Concentration (GMC) | 109 ELISA Units/mL |
| PNC13, Older Infants | Anti-Vi ELISA Geometric Mean Concentration (GMC) | 1.43 ELISA Units/mL |
| Vi-CRM, Infants | Anti-Vi ELISA Geometric Mean Concentration (GMC) | 23 ELISA Units/mL |
| PNC13, Infants | Anti-Vi ELISA Geometric Mean Concentration (GMC) | 2.33 ELISA Units/mL |
Primary
Anti-Vi ELISA GMC
Time frame: At 6 months after last vaccination
Population: Intention-to-treat analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Vi-CRM, Adults | Anti-Vi ELISA GMC | 59 ELISA Units/mL |
| Vi-PS, Adults | Anti-Vi ELISA GMC | 36 ELISA Units/mL |
| Vi-CRM, Children | Anti-Vi ELISA GMC | 23 ELISA Units/mL |
| Vi-PS, Children | Anti-Vi ELISA GMC | 25 ELISA Units/mL |
| Vi-CRM, Older Infants | Anti-Vi ELISA GMC | 22 ELISA Units/mL |
| PNC13, Older Infants | Anti-Vi ELISA GMC | 3.12 ELISA Units/mL |
| Vi-CRM, Infants | Anti-Vi ELISA GMC | 3.76 ELISA Units/mL |
| PNC13, Infants | Anti-Vi ELISA GMC | 1.41 ELISA Units/mL |
Primary
Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer
Time frame: At 6 months after last vaccination as compared to baseline
Population: Intention-to-treat analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vi-CRM, Adults | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer | 90 percentage of subjects |
| Vi-PS, Adults | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer | 81 percentage of subjects |
| Vi-CRM, Children | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer | 95 percentage of subjects |
| Vi-PS, Children | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer | 68 percentage of subjects |
| Vi-CRM, Older Infants | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer | 89 percentage of subjects |
| PNC13, Older Infants | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer | 6 percentage of subjects |
| Vi-CRM, Infants | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer | 25 percentage of subjects |
| PNC13, Infants | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer | 0 percentage of subjects |
Primary
Percentage of Subjects With at Least 4-fold Increase in Anti-Vi Enzyme-linked Immunosorbent Assay (ELISA) Titer
Time frame: At 28 days after last vaccination as compared to baseline
Population: Intention-to-treat analysis set, which included all participants who received the vaccination, those in whom at least one post-vaccination blood sample was collected, and those for whom at least one ELISA result was available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vi-CRM, Adults | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi Enzyme-linked Immunosorbent Assay (ELISA) Titer | 100 percentage of subjects |
| Vi-PS, Adults | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi Enzyme-linked Immunosorbent Assay (ELISA) Titer | 85 percentage of subjects |
| Vi-CRM, Children | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi Enzyme-linked Immunosorbent Assay (ELISA) Titer | 100 percentage of subjects |
| Vi-PS, Children | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi Enzyme-linked Immunosorbent Assay (ELISA) Titer | 89 percentage of subjects |
| Vi-CRM, Older Infants | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi Enzyme-linked Immunosorbent Assay (ELISA) Titer | 95 percentage of subjects |
| PNC13, Older Infants | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi Enzyme-linked Immunosorbent Assay (ELISA) Titer | 0 percentage of subjects |
| Vi-CRM, Infants | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi Enzyme-linked Immunosorbent Assay (ELISA) Titer | 85 percentage of subjects |
| PNC13, Infants | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi Enzyme-linked Immunosorbent Assay (ELISA) Titer | 6 percentage of subjects |
Secondary
Number of Participants With Any Solicited Local and Systemic Reaction, After Any Vaccination
Solicited local reactions were: Adults, children, older infants, infants: erythema, induration and pain/tenderness at the injection site. Solicited systemic reactions were: Adults: chills, malaise, myalgia, arthralgia, headache, fatigue, rash and fever. Children, older infants and infants: lethargy, irritability, vomiting, diarrhoea, loss of appetite, rash and fever (and persistent crying in infants).
Time frame: During the 7-day follow-up period after vaccination
Population: Analysis was done on as treated safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vi-CRM, Adults | Number of Participants With Any Solicited Local and Systemic Reaction, After Any Vaccination | 24 participants |
| Vi-PS, Adults | Number of Participants With Any Solicited Local and Systemic Reaction, After Any Vaccination | 27 participants |
| Vi-CRM, Children | Number of Participants With Any Solicited Local and Systemic Reaction, After Any Vaccination | 18 participants |
| Vi-PS, Children | Number of Participants With Any Solicited Local and Systemic Reaction, After Any Vaccination | 17 participants |
| Vi-CRM, Older Infants | Number of Participants With Any Solicited Local and Systemic Reaction, After Any Vaccination | 14 participants |
| PNC13, Older Infants | Number of Participants With Any Solicited Local and Systemic Reaction, After Any Vaccination | 19 participants |
| Vi-CRM, Infants | Number of Participants With Any Solicited Local and Systemic Reaction, After Any Vaccination | 20 participants |
| PNC13, Infants | Number of Participants With Any Solicited Local and Systemic Reaction, After Any Vaccination | 19 participants |