Bacterial Infections, Salmonella Infections, Typhoid Fever
Conditions
Keywords
Salmonella infections, Typhoid fever, Bacterial infections, Typhoid vaccine
Brief summary
This study is designed to assess the immunogenicity and safety of typhoid Vi polysaccharide vaccine in Japanese participants to support registration of the product in Japan. Primary Objective: To describe the seroconversion rate (percentage of subjects with at least a 4-fold increase of their Vi antibody titer) between Day 0 before vaccination and Day 28 after vaccination with typhoid Vi polysaccharide (SP093) vaccine in subjects aged 2 years and above. Secondary Objectives: * To describe the safety profile of a single dose of typhoid Vi polysaccharide vaccine up to 28 days after vaccination, in subjects aged 2 years and above. * To describe the immune response following a single dose of typhoid Vi polysaccharide vaccine in subjects aged 2 years and above.
Detailed description
All participants will receive a single dose of typhoid Vi polysaccharide vaccine on Day 0 and be assessed for immunogenicity on Day 0 before vaccination and on Day 28 post-vaccination. All participants will be monitored for safety for up to 28 days post-vaccination.
Interventions
BIOLOGICALTyphoid Vi polysaccharide
0.5 mL, Intramuscular
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Aged 2 years and above on the day of inclusion * For subjects ≥ 20 years of age: Informed consent form has been signed and dated by the subjects. For subjects 2 to 19 years of age: Informed consent form has been signed and dated by the parent or other legally representative. Also subjects 7 to 11 years of age will provide oral assent and subjects 12 to 19 years of age will provide written assent form * Able to attend all scheduled visits/phone call and to comply with all trial procedures * For a woman of childbearing potential, use of an effective method of contraception from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination.
Exclusion criteria
* Any acute and/or serious disease/illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion * History of typhoid fever or Salmonella typhi infection, confirmed either clinically, serologically, or microbiologically * Known systemic hypersensitivity to any of the vaccine components, or history of a life threatening reaction to a vaccine containing the same substances of the study vaccine * Known or suspected congenital or current/previous acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroids therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months) * Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the trial inclusion * Planned participation in another clinical trial during the present trial period * Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response * Receipt of any vaccine within the four weeks preceding the trial vaccination, except for influenza vaccination, which may be received at least two weeks before the study vaccine * Planned receipt of any vaccine during the trial period * Clinical or known serological evidence of systemic illness including hepatitis B, hepatitis C and/or Human immunodeficiency virus (HIV) infection * Ineligible according to the investigator's clinical judgment * Known pregnancy, or a positive (serum and/or urine) pregnancy test * Currently breastfeeding a child * Known thrombocytopenia, contraindicating intramuscular (IM) vaccination * Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM vaccination * Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily * Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures * Identified as employee of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family member (i.e., immediate, husband, wife and their children, adopted or natural) of the employees or the Investigator * Previous vaccination against Salmonella typhi disease with either the trial vaccine or another vaccine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With At Least a 4-Fold Rise in Vi Antibody Titers Following Vaccination With a Typhoid Vi Polysaccharide Vaccine | Day 0 (pre-vaccination) to Day 28 (post-vaccination) | Anti Vi antibodies were measured by Enzyme-Linked ImmunoSorbent Assay (ELISA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers (GMTs) of Antibodies to Vi Antibody Before and Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Day 0 (pre-vaccination) and Day 28 post-vaccination | Anti-Vi antibodies were measured by enzyme-linked immunosorbent assay (ELISA) |
| Geometric Mean Titer Ratios (GMTRs) of Antibodies to Vi Antibody Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Day 28 post-vaccination | Anti-Vi antibodies were measured by enzyme-linked immunosorbent assay (ELISA). |
| Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Day 0 up to Day 7 post-vaccination | Solicited injection site: Pain, Erythema, and Swelling; Solicited systemic reactions: Fever (Temperature), Headache, Malaise, Myalgia. Grade 3 injection site (children): Pain Incapacitating, unable to perform usual activities; Erythema and Swelling ≥ 50 mm; Grade 3 injection site (adults and adolescents): Pain, Significant, prevents daily activity; Erythema and Swelling, \>100 mm. Grade 3 systemic reactions: Fever, ≥39˚C; Headache, Malaise, and Myalgia, Significant, prevents daily activity. |
Countries
Japan
Participant flow
Recruitment details
The study participants were enrolled from 26 May 2012 to 31 August 2012 at 4 clinic centers in Japan.
Pre-assignment details
A total of 200 participants who met all of the inclusion and none of the exclusion criteria were vaccinated in this study.
Participants by arm
| Arm | Count |
|---|---|
| Adults (Group 1) Participants ≥18 years of age received a single dose (0.5 mL) of Typhoid Vi Polysaccharide Vaccine | 188 |
| Adolescents (Group 2) Participants 12 to 17 years of age received a single dose (0.5 mL) of Typhoid Vi Polysaccharide Vaccine | 7 |
| Children (Group 3) Participants 2 to 11 years of age received a single dose (0.5 mL) of Typhoid Vi Polysaccharide Vaccine | 5 |
| Total | 200 |
Baseline characteristics
| Characteristic | Adolescents (Group 2) | Children (Group 3) | Adults (Group 1) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 7 Participants | 5 Participants | 0 Participants | 12 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 188 Participants | 188 Participants |
| Age, Continuous | 15.6 Years STANDARD_DEVIATION 2 | 5.2 Years STANDARD_DEVIATION 3.8 | 37.2 Years STANDARD_DEVIATION 11.4 | 35.7 Years STANDARD_DEVIATION 12.7 |
| Region of Enrollment Japan | 7 Participants | 5 Participants | 188 Participants | 200 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 72 Participants | 76 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 116 Participants | 124 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 | 139 / 188 | 6 / 7 | 3 / 5 |
| serious Total, serious adverse events | 1 / 188 | 0 / 7 | 0 / 5 |
Outcome results
Primary
Number of Participants With At Least a 4-Fold Rise in Vi Antibody Titers Following Vaccination With a Typhoid Vi Polysaccharide Vaccine
Anti Vi antibodies were measured by Enzyme-Linked ImmunoSorbent Assay (ELISA).
Time frame: Day 0 (pre-vaccination) to Day 28 (post-vaccination)
Population: Vi antibody titers were assessed in the Immunology Analysis Set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adults (Group 1) | Number of Participants With At Least a 4-Fold Rise in Vi Antibody Titers Following Vaccination With a Typhoid Vi Polysaccharide Vaccine | 173 Participants |
| Dolescents (Group 2) | Number of Participants With At Least a 4-Fold Rise in Vi Antibody Titers Following Vaccination With a Typhoid Vi Polysaccharide Vaccine | 6 Participants |
| Children (Group 3) | Number of Participants With At Least a 4-Fold Rise in Vi Antibody Titers Following Vaccination With a Typhoid Vi Polysaccharide Vaccine | 5 Participants |
Secondary
Geometric Mean Titer Ratios (GMTRs) of Antibodies to Vi Antibody Following Vaccination With A Typhoid Vi Polysaccharide Vaccine
Anti-Vi antibodies were measured by enzyme-linked immunosorbent assay (ELISA).
Time frame: Day 28 post-vaccination
Population: Geometric Mean Titer Ratios were assessed in the Immunology Analysis Set.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Adults (Group 1) | Geometric Mean Titer Ratios (GMTRs) of Antibodies to Vi Antibody Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | 22.6 Ratio |
| Dolescents (Group 2) | Geometric Mean Titer Ratios (GMTRs) of Antibodies to Vi Antibody Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | 31.4 Ratio |
| Children (Group 3) | Geometric Mean Titer Ratios (GMTRs) of Antibodies to Vi Antibody Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | 135.6 Ratio |
Secondary
Geometric Mean Titers (GMTs) of Antibodies to Vi Antibody Before and Following Vaccination With A Typhoid Vi Polysaccharide Vaccine
Anti-Vi antibodies were measured by enzyme-linked immunosorbent assay (ELISA)
Time frame: Day 0 (pre-vaccination) and Day 28 post-vaccination
Population: Geometric Mean Titers were assessed in the Immunology Analysis Set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Adults (Group 1) | Geometric Mean Titers (GMTs) of Antibodies to Vi Antibody Before and Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | GMT (pre-vaccination) | 6.6 Titers |
| Adults (Group 1) | Geometric Mean Titers (GMTs) of Antibodies to Vi Antibody Before and Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | GMT (post-vaccination) | 148.6 Titers |
| Dolescents (Group 2) | Geometric Mean Titers (GMTs) of Antibodies to Vi Antibody Before and Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | GMT (pre-vaccination) | 10.2 Titers |
| Dolescents (Group 2) | Geometric Mean Titers (GMTs) of Antibodies to Vi Antibody Before and Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | GMT (post-vaccination) | 320.0 Titers |
| Children (Group 3) | Geometric Mean Titers (GMTs) of Antibodies to Vi Antibody Before and Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | GMT (pre-vaccination) | 3.7 Titers |
| Children (Group 3) | Geometric Mean Titers (GMTs) of Antibodies to Vi Antibody Before and Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | GMT (post-vaccination) | 501.7 Titers |
Secondary
Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine
Solicited injection site: Pain, Erythema, and Swelling; Solicited systemic reactions: Fever (Temperature), Headache, Malaise, Myalgia. Grade 3 injection site (children): Pain Incapacitating, unable to perform usual activities; Erythema and Swelling ≥ 50 mm; Grade 3 injection site (adults and adolescents): Pain, Significant, prevents daily activity; Erythema and Swelling, \>100 mm. Grade 3 systemic reactions: Fever, ≥39˚C; Headache, Malaise, and Myalgia, Significant, prevents daily activity.
Time frame: Day 0 up to Day 7 post-vaccination
Population: Solicited injection site reactions and systemic reactions were assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults (Group 1) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Malaise | 23 Participants |
| Adults (Group 1) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Injection site Swelling | 0 Participants |
| Adults (Group 1) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Injection site Erythema | 0 Participants |
| Adults (Group 1) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Headache | 1 Participants |
| Adults (Group 1) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Fever | 2 Participants |
| Adults (Group 1) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Injection site Pain | 0 Participants |
| Adults (Group 1) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Headache | 14 Participants |
| Adults (Group 1) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Fever | 0 Participants |
| Adults (Group 1) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Malaise | 2 Participants |
| Adults (Group 1) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Injection site Erythema | 0 Participants |
| Adults (Group 1) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Myalgia | 2 Participants |
| Adults (Group 1) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Injection site Pain | 139 Participants |
| Adults (Group 1) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Injection site Swelling | 1 Participants |
| Adults (Group 1) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Myalgia | 93 Participants |
| Dolescents (Group 2) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Malaise | 0 Participants |
| Dolescents (Group 2) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Injection site Pain | 6 Participants |
| Dolescents (Group 2) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Injection site Pain | 0 Participants |
| Dolescents (Group 2) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Injection site Erythema | 0 Participants |
| Dolescents (Group 2) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Injection site Erythema | 0 Participants |
| Dolescents (Group 2) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Injection site Swelling | 0 Participants |
| Dolescents (Group 2) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Injection site Swelling | 0 Participants |
| Dolescents (Group 2) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Fever | 0 Participants |
| Dolescents (Group 2) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Fever | 0 Participants |
| Dolescents (Group 2) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Headache | 0 Participants |
| Dolescents (Group 2) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Headache | 0 Participants |
| Dolescents (Group 2) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Malaise | 0 Participants |
| Dolescents (Group 2) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Myalgia | 4 Participants |
| Dolescents (Group 2) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Myalgia | 0 Participants |
| Children (Group 3) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Myalgia | 1 Participants |
| Children (Group 3) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Headache | 0 Participants |
| Children (Group 3) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Injection site Swelling | 0 Participants |
| Children (Group 3) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Injection site Erythema | 0 Participants |
| Children (Group 3) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Malaise | 0 Participants |
| Children (Group 3) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Injection site Erythema | 2 Participants |
| Children (Group 3) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Injection site Pain | 3 Participants |
| Children (Group 3) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Malaise | 0 Participants |
| Children (Group 3) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Injection site Pain | 0 Participants |
| Children (Group 3) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Fever | 0 Participants |
| Children (Group 3) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Fever | 1 Participants |
| Children (Group 3) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Myalgia | 0 Participants |
| Children (Group 3) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Headache | 0 Participants |
| Children (Group 3) | Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Following Vaccination With A Typhoid Vi Polysaccharide Vaccine | Grade 3 Injection site Swelling | 0 Participants |