Diphtheria
Conditions
Keywords
Primary immunization, Immunogenicity, Safety, Diphtheria, Tetanus, Acellular pertussis, Hepatitis B, Inactivated poliovirus, Haemophilus influenzae type b
Brief summary
The purpose of this study was to assess the safety and immunogenicity of GSK's combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and Haemophilus influenzae type b conjugate vaccine (DTPa-HBV-IPV/Hib) versus MCM Vaccine BV's DTaP5-HBV-IPV-Hib vaccine administered to healthy infants and toddlers, between 6 and 12 weeks of age at the time of first vaccination, based on a 2-, 4-, and 12-months of age vaccination schedule.
Interventions
BIOLOGICALDTPa-HBV-IPV/Hib
3 doses (1 each at 2, 4 and 12 months of age) of DTPa-HBV-IPV/Hib vaccine administered by intramuscular injection into the right thigh
BIOLOGICALDTaP5-HBV-IPV-Hib
3 doses (1 each at 2, 4 and 12 months of age) of DTaP5-HBV-IPV-Hib vaccine administered by intramuscular injection into the right thigh
BIOLOGICALPneumococcal 13-valent conjugate vaccine
3 doses (1 each at 2, 4 and 12 months of age) of pneumococcal 13-valent conjugate vaccine administered by intramuscular injection into the left thigh
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 12 Weeks
Healthy volunteers
Yes
Inclusion criteria
* Subjects' parent(s)/Legally Acceptable Representative(s) (LAR\[s\]) who, in the opinion of the investigator, could and would comply with the requirements of the protocol (e.g., return for follow-up visits). * Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure. * A male or female child between and including 6 and 12 weeks of age (42 to 84 days) at the time of the first vaccination. * Subject born after at least 37 weeks of gestation. * Healthy subjects as established by the investigator based on medical history and the clinical examination before entering into the study.
Exclusion criteria
* Any clinical condition that, in the opinion of the investigator, might pose any risk to the subject due to participation in the study. As with other vaccines, administration of DTPa-HBV-IPV/Hib should be postponed in subjects suffering from acute severe febrile illness. The presence of a minor infection is not a contraindication. * Known history of diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Hib diseases since birth. * History of any reaction or hypersensitivity likely to be caused or exacerbated by any excipient or active component of the vaccine(s). * Any confirmed or suspected immunosuppressive or immunodeficient condition, including malignancies, based on medical history and physical examination (no laboratory testing required). * Family history of congenital or hereditary immunodeficiency. * Major congenital defects, as assessed by the investigator. * Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined via medical history including physical examination. * Medical history of neurological disorder, including seizures. * Previous vaccination for diphtheria, tetanus, pertussis, HBV, poliomyelitis, Hib diseases and previous vaccination against pneumococcal infection with pneumococcal conjugate vaccine, with the exception of a birth dose of HBV vaccine, which may have been given in accordance with local recommendations. * Use of any investigational or non-registered product (drug, vaccine, or medical device) other than the study vaccine(s) during the period starting 30 days before the first dose of study vaccine(s) (Day -29 to Day 1), or planned use during the study period. * Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of vaccine(s) with the exception of administration of vaccines given as part of the national immunization schedule and as part of routine vaccination practice, e.g., rotavirus vaccine, that were allowed at any time during the study period. In case emergency mass vaccination for an unforeseen public health threat (e.g., a pandemic) would have been organized by public health authorities outside the routine immunization program, the time period described above could be reduced if necessary for that mass vaccination vaccine, provided this vaccine/product(s) is licensed and used according to its Product Information. * Administration of long-acting immune-modifying drugs in the period starting 30 days before the first dose and at any time during the study period. * Administration of immunoglobulins and/or any blood products or plasma derivatives from birth or planned administration during the study period. * Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first vaccine. For corticosteroids, this would mean prednisone ≥0.5 mg/kg/day (for paediatric subjects), or equivalent. Inhaled and topical steroids are allowed. * Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or would have been exposed to an investigational or a non-investigational vaccine/product (drug or medical device). * Child in care.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations at Month 11, Based on Per Protocol Set (PPS) | At Month 11 (i.e., 1-month post-booster vaccination) | Anti-PRP antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in microgram per milliliter (μg/mL), as assessed by Enzyme-linked immunosorbent assay (ELISA). |
| Percentage of Subjects With Anti-PRP Antibody Concentrations Equal to or Above (≥) 5 µg/mL at Month 11, Based on PPS | At Month 11 (i.e., 1-month post-booster vaccination) | The percentage of subjects with anti-PRP antibody concentrations ≥5 µg/mL was reported, as assessed by ELISA. |
| Anti-PRP Antibody Concentrations at Month 11, Based on the Exposed Set (ES) | At Month 11 (i.e., 1-month post-booster vaccination) | Anti-PRP antibody concentrations were presented as GMCs and expressed in μg/mL, as assessed by ELISA. |
| Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 5 µg/mL at Month 11, Based on ES | At Month 11 (i.e., 1-month post-booster vaccination) | The percentage of subjects with anti-PRP antibody concentrations ≥5 µg/mL was reported, as assessed by ELISA. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Anti-PRP Antibody Concentration ≥ 0.15 µg/mL | At Month 3 (i.e., 1-month post-primary vaccination), Month 10 (i.e., pre-booster) and Month 11 (i.e., 1-month post-booster vaccination) | The percentage of subjects with anti-PRP antibody concentration equal to or above the threshold for short-term protection was reported. The threshold for short-term protection is 0.15 µg/mL. |
| Number of Subjects With Serious Adverse Events (SAEs) | Throughout the entire period of the study (from Day 1 up to study end [Month 11]) | A SAEs is defined as any untoward medical occurrence that, at any dose, result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect. |
| Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 1.0 µg/mL | At Month 3 (i.e., 1-month post-primary vaccination), Month 10 (i.e., pre-booster) and Month 11 (i.e., 1-month post-booster vaccination) | The percentage of subjects with anti-PRP antibody concentration equal to or above the threshold for long-term protection was reported. The threshold for long-term protection is 1.0 µg/mL. |
| Anti-PRP Antibody Concentrations | At Month 3 (i.e., 1-month post-primary vaccination), Month 10 (i.e., pre-booster) and Month 11 (i.e., 1-month post-booster vaccination) | Anti-PRP antibody concentrations were presented as GMCs and expressed in μg/mL, as assessed by ELISA. |
| Number of Subjects With Unsolicited Adverse Events (AEs) | During the 31-day (Days 1-31) follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age) | AEs are defined as any untoward medical occurrence in a subject or subjects, temporally associated with the use of study treatment, whether or not considered related to the study treatment. |
Countries
Germany, Italy, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Infanrix Hexa All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTPa-HBV-IPV/Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age. | 249 |
| Vaxelis All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTaP5 HBV IPV Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age. | 251 |
| Total | 500 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Migrated / moved from the study area | 1 | 4 |
| Overall Study | Other | 2 | 5 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 8 | 9 |
Baseline characteristics
| Characteristic | Vaxelis | Total | Infanrix Hexa |
|---|---|---|---|
| Age, Continuous | 8.6 Weeks STANDARD_DEVIATION 1.24 | 8.6 Weeks STANDARD_DEVIATION 1.2 | 8.6 Weeks STANDARD_DEVIATION 1.17 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - Central / South Asian Heritage | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Other-Unspecified | 6 Participants | 11 Participants | 5 Participants |
| Race/Ethnicity, Customized White - Arabic / North African Heritage | 4 Participants | 9 Participants | 5 Participants |
| Race/Ethnicity, Customized White - Caucasian / European Heritage | 235 Participants | 471 Participants | 236 Participants |
| Sex: Female, Male Female | 135 Participants | 240 Participants | 105 Participants |
| Sex: Female, Male Male | 116 Participants | 260 Participants | 144 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 249 | 0 / 251 |
| other Total, other adverse events | 178 / 249 | 199 / 251 |
| serious Total, serious adverse events | 14 / 249 | 10 / 251 |
Outcome results
Primary
Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations at Month 11, Based on Per Protocol Set (PPS)
Anti-PRP antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in microgram per milliliter (μg/mL), as assessed by Enzyme-linked immunosorbent assay (ELISA).
Time frame: At Month 11 (i.e., 1-month post-booster vaccination)
Population: The analysis was performed on the Per Protocol Set (PPS), which included all eligible subjects who received diphtheria, tetanus and acellular pertussis (DTPa)-combination study vaccines as per protocol, who had anti-PRP results post-vaccination, who complied with vaccination/blood draw intervals, without intercurrent conditions and without prohibited concomitant medication/vaccination and for whom immunogenicity data were available for specific timepoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Infanrix Hexa | Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations at Month 11, Based on Per Protocol Set (PPS) | 11.61 μg/mL |
| Vaxelis | Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations at Month 11, Based on Per Protocol Set (PPS) | 12.66 μg/mL |
Comparison: To demonstrate that the Haemophilus influenzae type b(Hib) response of Infanrix Hexa Group is non-inferior to the Vaxelis Group in terms of anti-PRP GMCs, 1 month post-booster vaccination.95% CI: [0.71, 1.185]
Primary
Anti-PRP Antibody Concentrations at Month 11, Based on the Exposed Set (ES)
Anti-PRP antibody concentrations were presented as GMCs and expressed in μg/mL, as assessed by ELISA.
Time frame: At Month 11 (i.e., 1-month post-booster vaccination)
Population: The analysis was performed on the Exposed Set (ES), which included all vaccinated subjects who were analysed according to the intervention they received at Dose 1 and for whom immunogenicity data were available for specific timepoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Infanrix Hexa | Anti-PRP Antibody Concentrations at Month 11, Based on the Exposed Set (ES) | 11.26 μg/mL |
| Vaxelis | Anti-PRP Antibody Concentrations at Month 11, Based on the Exposed Set (ES) | 12.85 μg/mL |
Primary
Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 5 µg/mL at Month 11, Based on ES
The percentage of subjects with anti-PRP antibody concentrations ≥5 µg/mL was reported, as assessed by ELISA.
Time frame: At Month 11 (i.e., 1-month post-booster vaccination)
Population: The analysis was performed on the ES, which included all vaccinated subjects who were analysed according to the intervention they received at Dose 1 and for whom immunogenicity data were available for specific timepoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infanrix Hexa | Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 5 µg/mL at Month 11, Based on ES | 75.4 Percentage of Participants |
| Vaxelis | Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 5 µg/mL at Month 11, Based on ES | 81.6 Percentage of Participants |
Primary
Percentage of Subjects With Anti-PRP Antibody Concentrations Equal to or Above (≥) 5 µg/mL at Month 11, Based on PPS
The percentage of subjects with anti-PRP antibody concentrations ≥5 µg/mL was reported, as assessed by ELISA.
Time frame: At Month 11 (i.e., 1-month post-booster vaccination)
Population: The analysis was performed on PPS, which included all eligible subjects who received all DTPa-combination study vaccines as per protocol, who had anti-PRP results post-vaccination, who complied with vaccination/blood draw intervals, without intercurrent conditions and without prohibited concomitant medication/vaccination and for whom immunogenicity data were available for specific timepoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infanrix Hexa | Percentage of Subjects With Anti-PRP Antibody Concentrations Equal to or Above (≥) 5 µg/mL at Month 11, Based on PPS | 75.4 Percentage of Participants |
| Vaxelis | Percentage of Subjects With Anti-PRP Antibody Concentrations Equal to or Above (≥) 5 µg/mL at Month 11, Based on PPS | 81.7 Percentage of Participants |
Comparison: To demonstrate that the Hib response in Infanrix Hexa group is non-inferior to Vaxelis Group in terms of percentage of subjects with anti-PRP antibody concentrations ≥ 5 µg/mL, 1 month post-booster vaccination.95% CI: [-14.1, 1.49]
Secondary
Anti-PRP Antibody Concentrations
Anti-PRP antibody concentrations were presented as GMCs and expressed in μg/mL, as assessed by ELISA.
Time frame: At Month 3 (i.e., 1-month post-primary vaccination), Month 10 (i.e., pre-booster) and Month 11 (i.e., 1-month post-booster vaccination)
Population: The analysis was performed on PPS, which included all eligible subjects who received all DTPa-combination study vaccines as per protocol, who had anti-PRP results post-vaccination, who complied with vaccination/blood draw intervals, without intercurrent conditions and without prohibited concomitant medication/vaccination and for whom immunogenicity data were available for specific timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Infanrix Hexa | Anti-PRP Antibody Concentrations | At Month 3 | 0.5 μg/mL |
| Infanrix Hexa | Anti-PRP Antibody Concentrations | At Month 10 | 0.2 μg/mL |
| Infanrix Hexa | Anti-PRP Antibody Concentrations | At Month 11 | 12.0 μg/mL |
| Vaxelis | Anti-PRP Antibody Concentrations | At Month 3 | 11.3 μg/mL |
| Vaxelis | Anti-PRP Antibody Concentrations | At Month 10 | 1.9 μg/mL |
| Vaxelis | Anti-PRP Antibody Concentrations | At Month 11 | 12.9 μg/mL |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
A SAEs is defined as any untoward medical occurrence that, at any dose, result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect.
Time frame: Throughout the entire period of the study (from Day 1 up to study end [Month 11])
Population: The analysis was performed on the ES, which included all vaccinated subjects who were analysed according to the intervention they received at Dose 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Infanrix Hexa | Number of Subjects With Serious Adverse Events (SAEs) | 14 Participants |
| Vaxelis | Number of Subjects With Serious Adverse Events (SAEs) | 10 Participants |
Secondary
Number of Subjects With Unsolicited Adverse Events (AEs)
AEs are defined as any untoward medical occurrence in a subject or subjects, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time frame: During the 31-day (Days 1-31) follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age)
Population: The analysis was performed on the ES, which included all vaccinated subjects who were analysed according to the intervention they received at Dose 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Infanrix Hexa | Number of Subjects With Unsolicited Adverse Events (AEs) | 178 Participants |
| Vaxelis | Number of Subjects With Unsolicited Adverse Events (AEs) | 199 Participants |
Secondary
Percentage of Subjects With Anti-PRP Antibody Concentration ≥ 0.15 µg/mL
The percentage of subjects with anti-PRP antibody concentration equal to or above the threshold for short-term protection was reported. The threshold for short-term protection is 0.15 µg/mL.
Time frame: At Month 3 (i.e., 1-month post-primary vaccination), Month 10 (i.e., pre-booster) and Month 11 (i.e., 1-month post-booster vaccination)
Population: The analysis was performed on PPS, which included all eligible subjects who received all DTPa-combination study vaccines as per protocol, who had anti-PRP results post-vaccination, who complied with vaccination/blood draw intervals, without intercurrent conditions and without prohibited concomitant medication/vaccination and for whom immunogenicity data were available for specific timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infanrix Hexa | Percentage of Subjects With Anti-PRP Antibody Concentration ≥ 0.15 µg/mL | At month 3 | 79.8 Percentage of Participants |
| Infanrix Hexa | Percentage of Subjects With Anti-PRP Antibody Concentration ≥ 0.15 µg/mL | At Month 10 | 61.2 Percentage of Participants |
| Infanrix Hexa | Percentage of Subjects With Anti-PRP Antibody Concentration ≥ 0.15 µg/mL | At Month 11 | 99.5 Percentage of Participants |
| Vaxelis | Percentage of Subjects With Anti-PRP Antibody Concentration ≥ 0.15 µg/mL | At month 3 | 100 Percentage of Participants |
| Vaxelis | Percentage of Subjects With Anti-PRP Antibody Concentration ≥ 0.15 µg/mL | At Month 10 | 94.4 Percentage of Participants |
| Vaxelis | Percentage of Subjects With Anti-PRP Antibody Concentration ≥ 0.15 µg/mL | At Month 11 | 99.5 Percentage of Participants |
Secondary
Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 1.0 µg/mL
The percentage of subjects with anti-PRP antibody concentration equal to or above the threshold for long-term protection was reported. The threshold for long-term protection is 1.0 µg/mL.
Time frame: At Month 3 (i.e., 1-month post-primary vaccination), Month 10 (i.e., pre-booster) and Month 11 (i.e., 1-month post-booster vaccination)
Population: The analysis was performed on PPS, which included all eligible subjects who received all DTPa-combination study vaccines as per protocol, who had anti-PRP results post-vaccination, who complied with vaccination/blood draw intervals, without intercurrent conditions and without prohibited concomitant medication/vaccination and for whom immunogenicity data were available for specific timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infanrix Hexa | Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 1.0 µg/mL | At Month 3 | 30.5 Percentage of Participants |
| Infanrix Hexa | Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 1.0 µg/mL | At Month 10 | 13.1 Percentage of Participants |
| Infanrix Hexa | Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 1.0 µg/mL | At Month 11 | 97.2 Percentage of Participants |
| Vaxelis | Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 1.0 µg/mL | At Month 3 | 92.2 Percentage of Participants |
| Vaxelis | Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 1.0 µg/mL | At Month 10 | 69.0 Percentage of Participants |
| Vaxelis | Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 1.0 µg/mL | At Month 11 | 94.5 Percentage of Participants |