Hepatitis B, Pertussis
Conditions
Keywords
Immune response
Brief summary
This is a multicenter extension study of two European randomized, double-blind studies (V419-007 and V419-008). It describes long-term persistence of hepatitis B and pertussis antibody responses in healthy 4- to 5 year old children previously vaccinated with Vaxelis® or INFANRIX® hexa
Interventions
OTHERBlood Sample
Blood sample at approx. 4 years of age
Sponsors
Merck Sharp & Dohme LLC
Sanofi Pasteur, a Sanofi Company
MCM Vaccines B.V.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 5 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy child of either gender, who has received a complete 3-dose primary series or a complete 2 dose primary series followed by a toddler dose with VAXELIS or INFANRIX hexa as part of the V419-007 or V419-008 study respectively. 2. Informed consent signed by the participant's parent(s) or legal representative.
Exclusion criteria
1. Participant who has received any dose of hepatitis B (HB)-containing vaccine at any time other than study vaccine in V419-007 or V419-008 study. 2. Participant with a history of diagnosis (clinical, serological or microbiological) of HB virus infection of the V419-007 or V419-008 study. 3. Participant who has received any dose of pertussis-containing vaccine after completion of the V419-008 study. 4. Participant with a history of diagnosis (clinical, serological or microbiological) of infection due to pertussis after completion of V419-008 study. 5. Participation at the time of study enrolment or in the 4 weeks preceding the study enrolment in another clinical study investigating a vaccine, drug medical device, or medical procedure\*. 6. Participant who received immunoglobulins, blood or blood-derived products within 3 months prior to inclusion\*. 7. Receipt of immunosuppressive therapy or other immune-modifying drugs, such as anti-cancer chemotherapy or radiation therapy since completion of V419-007 or V419-008 studies. 8. Participant with suspected or known blood dyscrasias, leukemia, lymphomas of any type or other malignant neoplasms affecting the haematopietic and lymphatic systems since completion of V419-007 or V419-008 studies. * Criteria 5 and 6 are temporary
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Responding to Pertussis Fimbriae | Day 1 (approximately 4 years after completion of the 2+1 schedule) | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae. LLOQ=4 EU/mL. Confidence Intervals were calculated based on the exact binomial method of D. Collett. |
| Percentage of Participants Responding to Hepatitis B Surface Antigen (HBsAg) | Day 1 (approximately 4 years after completion of the 3+1/2+1 schedule) | Participant serum samples were collected for testing with an enhanced chemiluminescence assay for antibodies to HBsAg. Response was defined as a titer \>=10 milli International units (mIU)/mL. Confidence Intervals were calculated based on the exact binomial method of D. Collett. |
| Percentage of Participants Responding to Pertussis Toxin | Day 1 (approximately 4 years after completion of the 2+1 schedule) | Participant serum samples were collected for testing with an Enzyme-linked Immunosorbent Assay (ELISA) for antibodies to pertussis toxin. The unit of measure is ELISA units/mL. The lower limit of quantification (LLOQ)=4 EU/mL. Confidence Intervals were calculated based on the exact binomial method of D. Collett. |
| Percentage of Participants Responding to Pertussis Filamentous Hemagglutinin | Day 1 (approximately 4 years after completion of the 2+1 schedule) | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis filamentous hemagglutinin. LLOQ=3 EU/mL. Confidence Intervals were calculated based on the exact binomial method of D. Collett. |
| Percentage of Participants Responding to Pertussis Pertactin | Day 1 (approximately 4 years after completion of the 2+1 schedule) | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin. LLOQ=4 EU/mL. Confidence Intervals were calculated based on the exact binomial method of D. Collett. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Concentration of Antibodies to Pertussis Fimbriae | Day 1 (approximately 4 years after completion of the 2+1 schedule) | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae. Confidence Intervals were calculated based on the t-distribution of the log-transformed antibody concentration. |
| Geometric Mean Concentration of Antibodies to HBsAg | Day 1 (approximately 4 years after completion of the 3+1 or 2+1 schedule) | Participant serum samples were collected for testing with an enhanced chemiluminescence assay for antibodies to HBsAg. The unit of measure is milli International Units/mL (mIU/mL). Confidence Intervals were calculated based on the t-distribution of the log-transformed antibody concentration. |
| Geometric Mean Concentration of Antibodies to Pertussis Toxin | Day 1 (approximately 4 years after completion of the 2+1 schedule) | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis toxin. The unit of measure is ELISA units/mL (EU/mL). Confidence Intervals were calculated based on the t-distribution of the log-transformed antibody concentration. |
| Geometric Mean Concentration of Antibodies to Pertussis Filamentous Hemagglutinin | Day 1 (approximately 4 years after completion of the 2+1 schedule) | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis filamentous hemagglutinin. Confidence Intervals were calculated based on the t-distribution of the log-transformed antibody concentration. |
| Geometric Mean Concentration of Antibodies to Pertussis Pertactin | Day 1 (approximately 4 years after completion of the 2+1 schedule) | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin. Confidence Intervals were calculated based on the t-distribution of the log-transformed antibody concentration. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With One or More Serious Adverse Events Related to Study Procedure | Up to 4 days following blood sample on Day 1 (approximately 4 years after completion of the 3+1 or 2+1 schedule) | An SAE is any untoward medical occurrence or effect that at any dose results in death or is life threatening. Life-threatening in this context refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it was more severe. |
Participant flow
Recruitment details
This multicenter extension study was conducted in Finland at approximately 10 sites from studies V419-007 and V419-008, which had eligible participants(i.e. participants who completed the full 3+1 or 2+1 vaccination schedule in the original studies).
Pre-assignment details
Of the 760 screened participants, 754 were enrolled and completed the study. A total of 752 participants were included in the Persistence Analysis Set, 752 with blood samples available for hepatitis B surface antigen (HBsAg) analyses, and 751 for pertussis analyses.
Participants by arm
| Arm | Count |
|---|---|
| Group Vaxelis (3+1) Participants previously vaccinated with a 3-dose primary series of Vaxelis® at 2, 3 and 4 months of age, and a toddler dose at 12 months of age (study V419-007). On Day 1 of this extension study (\
4 years after completion of the 3+1 schedule), a 4 mL blood sample was obtained to assay for long-term antibody persistence. | 191 |
| Group Infanrix Hexa (3+1) Participants previously vaccinated with a 3-dose primary series of INFANRIX® hexa at 2, 3 and 4 months of age, and a toddler dose at 12 months of age (study V419-007). On Day 1 of this extension study (\
4 years after completion of the 3+1 schedule), a 4 mL blood sample was obtained to assay for long-term antibody persistence. | 189 |
| Group Vaxelis (2+1) Participants previously vaccinated with a 2-dose primary series of Vaxelis® at 2 and 4 months of age, and a toddler dose at 11-12 months of age (study V419-008). On Day 1 of this extension study (\
4 years after completion of the 2+1 schedule), a 4 mL blood sample was obtained to assay for long-term antibody persistence. | 181 |
| Group Infanrix Hexa (2+1) Participants previously vaccinated with a 2-dose primary series of INFANRIX® hexa at 2 and 4 months of age, and a toddler dose at 11-12 months of age (study V419-008). On Day 1 of this extension study (\
4 years after completion of the 2+1 schedule), a 4 mL blood sample was obtained to assay for long-term antibody persistence. | 191 |
| Total | 752 |
Baseline characteristics
| Characteristic | Group Vaxelis (3+1) | Group Infanrix Hexa (3+1) | Group Vaxelis (2+1) | Group Infanrix Hexa (2+1) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 4.8 Years STANDARD_DEVIATION 0.2 | 4.8 Years STANDARD_DEVIATION 0.2 | 3.9 Years STANDARD_DEVIATION 0.1 | 3.9 Years STANDARD_DEVIATION 0.1 | 4.4 Years STANDARD_DEVIATION 0.4 |
| Sex: Female, Male Female | 98 Participants | 86 Participants | 84 Participants | 94 Participants | 362 Participants |
| Sex: Female, Male Male | 93 Participants | 103 Participants | 97 Participants | 97 Participants | 390 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 | 0 / 191 | 0 / 189 | 0 / 181 | 0 / 191 |
| serious Total, serious adverse events | 0 / 191 | 0 / 189 | 0 / 181 | 0 / 191 |
Outcome results
Primary
Percentage of Participants Responding to Hepatitis B Surface Antigen (HBsAg)
Participant serum samples were collected for testing with an enhanced chemiluminescence assay for antibodies to HBsAg. Response was defined as a titer \>=10 milli International units (mIU)/mL. Confidence Intervals were calculated based on the exact binomial method of D. Collett.
Time frame: Day 1 (approximately 4 years after completion of the 3+1/2+1 schedule)
Population: All analyses were performed on the Persistence Analysis Set, defined as all participants previously vaccinated (with a complete 3+1 or 2+1 schedule, as part of studies V419-007 or V419-008) with available immunogenicity data for the respective endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group Vaxelis (3+1) | Percentage of Participants Responding to Hepatitis B Surface Antigen (HBsAg) | 70.16 Percentage of Participants |
| Group Infanrix Hexa (3+1) | Percentage of Participants Responding to Hepatitis B Surface Antigen (HBsAg) | 82.01 Percentage of Participants |
| Group Vaxelis (2+1) | Percentage of Participants Responding to Hepatitis B Surface Antigen (HBsAg) | 65.75 Percentage of Participants |
| Group Infanrix Hexa (2+1) | Percentage of Participants Responding to Hepatitis B Surface Antigen (HBsAg) | 83.68 Percentage of Participants |
Primary
Percentage of Participants Responding to Pertussis Filamentous Hemagglutinin
Participant serum samples were collected for testing with an ELISA for antibodies to pertussis filamentous hemagglutinin. LLOQ=3 EU/mL. Confidence Intervals were calculated based on the exact binomial method of D. Collett.
Time frame: Day 1 (approximately 4 years after completion of the 2+1 schedule)
Population: The analysis population was the Persistence Analysis Set, all participants previously vaccinated with complete 2+1 schedule (V419-008) with available immunogenicity data for the respective endpoint. Due to pre-school enrollment and booster administration, assessment of pertussis antibody persistence was not possible for the 3+1 schedule (V419-007).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group Vaxelis (3+1) | Percentage of Participants Responding to Pertussis Filamentous Hemagglutinin | Concentration ≥LLOQ | 80.92 Percentage of participants |
| Group Vaxelis (3+1) | Percentage of Participants Responding to Pertussis Filamentous Hemagglutinin | Concentration ≥2×LLOQ | 46.82 Percentage of participants |
| Group Vaxelis (3+1) | Percentage of Participants Responding to Pertussis Filamentous Hemagglutinin | Concentration ≥4×LLOQ | 26.01 Percentage of participants |
| Group Infanrix Hexa (3+1) | Percentage of Participants Responding to Pertussis Filamentous Hemagglutinin | Concentration ≥LLOQ | 88.30 Percentage of participants |
| Group Infanrix Hexa (3+1) | Percentage of Participants Responding to Pertussis Filamentous Hemagglutinin | Concentration ≥2×LLOQ | 70.74 Percentage of participants |
| Group Infanrix Hexa (3+1) | Percentage of Participants Responding to Pertussis Filamentous Hemagglutinin | Concentration ≥4×LLOQ | 45.21 Percentage of participants |
Primary
Percentage of Participants Responding to Pertussis Fimbriae
Participant serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae. LLOQ=4 EU/mL. Confidence Intervals were calculated based on the exact binomial method of D. Collett.
Time frame: Day 1 (approximately 4 years after completion of the 2+1 schedule)
Population: The analysis population was the Persistence Analysis Set, all participants previously vaccinated with complete 2+1 schedule (V419-008) with available immunogenicity data for the respective endpoint. Due to pre-school enrollment and booster administration, assessment of pertussis antibody persistence was not possible for the 3+1 schedule (V419-007).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group Vaxelis (3+1) | Percentage of Participants Responding to Pertussis Fimbriae | Concentration ≥LLOQ | 94.35 Percentage of participants |
| Group Vaxelis (3+1) | Percentage of Participants Responding to Pertussis Fimbriae | Concentration ≥2×LLOQ | 88.14 Percentage of participants |
| Group Vaxelis (3+1) | Percentage of Participants Responding to Pertussis Fimbriae | Concentration ≥4×LLOQ | 69.49 Percentage of participants |
| Group Infanrix Hexa (3+1) | Percentage of Participants Responding to Pertussis Fimbriae | Concentration ≥LLOQ | 3.28 Percentage of participants |
| Group Infanrix Hexa (3+1) | Percentage of Participants Responding to Pertussis Fimbriae | Concentration ≥2×LLOQ | 2.19 Percentage of participants |
| Group Infanrix Hexa (3+1) | Percentage of Participants Responding to Pertussis Fimbriae | Concentration ≥4×LLOQ | 1.09 Percentage of participants |
Primary
Percentage of Participants Responding to Pertussis Pertactin
Participant serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin. LLOQ=4 EU/mL. Confidence Intervals were calculated based on the exact binomial method of D. Collett.
Time frame: Day 1 (approximately 4 years after completion of the 2+1 schedule)
Population: The analysis population was the Persistence Analysis Set, all participants previously vaccinated with complete 2+1 schedule (V419-008) with available immunogenicity data for the respective endpoint. Due to pre-school enrollment and booster administration, assessment of pertussis antibody persistence was not possible for the 3+1 schedule (V419-007).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group Vaxelis (3+1) | Percentage of Participants Responding to Pertussis Pertactin | Concentration ≥LLOQ | 66.11 Percentage of participants |
| Group Vaxelis (3+1) | Percentage of Participants Responding to Pertussis Pertactin | Concentration ≥2×LLOQ | 43.89 Percentage of participants |
| Group Vaxelis (3+1) | Percentage of Participants Responding to Pertussis Pertactin | Concentration ≥4×LLOQ | 15.56 Percentage of participants |
| Group Infanrix Hexa (3+1) | Percentage of Participants Responding to Pertussis Pertactin | Concentration ≥LLOQ | 72.63 Percentage of participants |
| Group Infanrix Hexa (3+1) | Percentage of Participants Responding to Pertussis Pertactin | Concentration ≥2×LLOQ | 51.05 Percentage of participants |
| Group Infanrix Hexa (3+1) | Percentage of Participants Responding to Pertussis Pertactin | Concentration ≥4×LLOQ | 18.42 Percentage of participants |
Primary
Percentage of Participants Responding to Pertussis Toxin
Participant serum samples were collected for testing with an Enzyme-linked Immunosorbent Assay (ELISA) for antibodies to pertussis toxin. The unit of measure is ELISA units/mL. The lower limit of quantification (LLOQ)=4 EU/mL. Confidence Intervals were calculated based on the exact binomial method of D. Collett.
Time frame: Day 1 (approximately 4 years after completion of the 2+1 schedule)
Population: The analysis population was the Persistence Analysis Set, all participants previously vaccinated with complete 2+1 schedule (V419-008) with available immunogenicity data for the respective endpoint. Due to pre-school enrollment and booster administration, assessment of pertussis antibody persistence was not possible for the 3+1 schedule (V419-007).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group Vaxelis (3+1) | Percentage of Participants Responding to Pertussis Toxin | Concentration ≥LLOQ | 58.43 Percentage of participants |
| Group Vaxelis (3+1) | Percentage of Participants Responding to Pertussis Toxin | Concentration ≥2×LLOQ | 40.45 Percentage of participants |
| Group Vaxelis (3+1) | Percentage of Participants Responding to Pertussis Toxin | Concentration ≥4×LLOQ | 14.61 Percentage of participants |
| Group Infanrix Hexa (3+1) | Percentage of Participants Responding to Pertussis Toxin | Concentration ≥LLOQ | 41.49 Percentage of participants |
| Group Infanrix Hexa (3+1) | Percentage of Participants Responding to Pertussis Toxin | Concentration ≥2×LLOQ | 21.81 Percentage of participants |
| Group Infanrix Hexa (3+1) | Percentage of Participants Responding to Pertussis Toxin | Concentration ≥4×LLOQ | 3.72 Percentage of participants |
Secondary
Geometric Mean Concentration of Antibodies to HBsAg
Participant serum samples were collected for testing with an enhanced chemiluminescence assay for antibodies to HBsAg. The unit of measure is milli International Units/mL (mIU/mL). Confidence Intervals were calculated based on the t-distribution of the log-transformed antibody concentration.
Time frame: Day 1 (approximately 4 years after completion of the 3+1 or 2+1 schedule)
Population: All analyses were performed on the Persistence Analysis Set, defined as all participants previously vaccinated (with a complete 3+1 or 2+1 schedule, as part of studies V419-007 or V419-008) with available immunogenicity data for the respective endpoint.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group Vaxelis (3+1) | Geometric Mean Concentration of Antibodies to HBsAg | 24.43 mIU/mL |
| Group Infanrix Hexa (3+1) | Geometric Mean Concentration of Antibodies to HBsAg | 51.30 mIU/mL |
| Group Vaxelis (2+1) | Geometric Mean Concentration of Antibodies to HBsAg | 19.44 mIU/mL |
| Group Infanrix Hexa (2+1) | Geometric Mean Concentration of Antibodies to HBsAg | 71.00 mIU/mL |
Secondary
Geometric Mean Concentration of Antibodies to Pertussis Filamentous Hemagglutinin
Participant serum samples were collected for testing with an ELISA for antibodies to pertussis filamentous hemagglutinin. Confidence Intervals were calculated based on the t-distribution of the log-transformed antibody concentration.
Time frame: Day 1 (approximately 4 years after completion of the 2+1 schedule)
Population: The analysis population was the Persistence Analysis Set, all participants previously vaccinated with complete 2+1 schedule (V419-008) with available immunogenicity data for the respective endpoint. Due to pre-school enrollment and booster administration, assessment of pertussis antibody persistence was not possible for the 3+1 schedule (V419-007).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group Vaxelis (3+1) | Geometric Mean Concentration of Antibodies to Pertussis Filamentous Hemagglutinin | 6.62 EU/mL |
| Group Infanrix Hexa (3+1) | Geometric Mean Concentration of Antibodies to Pertussis Filamentous Hemagglutinin | 11.05 EU/mL |
Secondary
Geometric Mean Concentration of Antibodies to Pertussis Fimbriae
Participant serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae. Confidence Intervals were calculated based on the t-distribution of the log-transformed antibody concentration.
Time frame: Day 1 (approximately 4 years after completion of the 2+1 schedule)
Population: The analysis population was the Persistence Analysis Set, all participants previously vaccinated with complete 2+1 schedule (V419-008) with available immunogenicity data for the respective endpoint. Due to pre-school enrollment and booster administration, assessment of pertussis antibody persistence was not possible for the 3+1 schedule (V419-007).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group Vaxelis (3+1) | Geometric Mean Concentration of Antibodies to Pertussis Fimbriae | 25.99 EU/mL |
| Group Infanrix Hexa (3+1) | Geometric Mean Concentration of Antibodies to Pertussis Fimbriae | 2.13 EU/mL |
Secondary
Geometric Mean Concentration of Antibodies to Pertussis Pertactin
Participant serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin. Confidence Intervals were calculated based on the t-distribution of the log-transformed antibody concentration.
Time frame: Day 1 (approximately 4 years after completion of the 2+1 schedule)
Population: The analysis population was the Persistence Analysis Set, all participants previously vaccinated with complete 2+1 schedule (V419-008) with available immunogenicity data for the respective endpoint. Due to pre-school enrollment and booster administration, assessment of pertussis antibody persistence was not possible for the 3+1 schedule (V419-007).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group Vaxelis (3+1) | Geometric Mean Concentration of Antibodies to Pertussis Pertactin | 5.94 EU/mL |
| Group Infanrix Hexa (3+1) | Geometric Mean Concentration of Antibodies to Pertussis Pertactin | 7.19 EU/mL |
Secondary
Geometric Mean Concentration of Antibodies to Pertussis Toxin
Participant serum samples were collected for testing with an ELISA for antibodies to pertussis toxin. The unit of measure is ELISA units/mL (EU/mL). Confidence Intervals were calculated based on the t-distribution of the log-transformed antibody concentration.
Time frame: Day 1 (approximately 4 years after completion of the 2+1 schedule)
Population: The analysis population was the Persistence Analysis Set, all participants previously vaccinated with complete 2+1 schedule (V419-008) with available immunogenicity data for the respective endpoint. Due to pre-school enrollment and booster administration, assessment of pertussis antibody persistence was not possible for the 3+1 schedule (V419-007).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group Vaxelis (3+1) | Geometric Mean Concentration of Antibodies to Pertussis Toxin | 5.31 EU/mL |
| Group Infanrix Hexa (3+1) | Geometric Mean Concentration of Antibodies to Pertussis Toxin | 3.64 EU/mL |
Other Pre-specified
Percentage of Participants With One or More Serious Adverse Events Related to Study Procedure
An SAE is any untoward medical occurrence or effect that at any dose results in death or is life threatening. Life-threatening in this context refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it was more severe.
Time frame: Up to 4 days following blood sample on Day 1 (approximately 4 years after completion of the 3+1 or 2+1 schedule)
Population: All analyses were performed on the Persistence Analysis Set, defined as all participants previously vaccinated (with a complete 3+1 or 2+1 schedule, as part of studies V419-007 or V419-008) with available immunogenicity data for the respective endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group Vaxelis (3+1) | Percentage of Participants With One or More Serious Adverse Events Related to Study Procedure | 0 Percentage of Participants |
| Group Infanrix Hexa (3+1) | Percentage of Participants With One or More Serious Adverse Events Related to Study Procedure | 0 Percentage of Participants |
| Group Vaxelis (2+1) | Percentage of Participants With One or More Serious Adverse Events Related to Study Procedure | 0 Percentage of Participants |
| Group Infanrix Hexa (2+1) | Percentage of Participants With One or More Serious Adverse Events Related to Study Procedure | 0 Percentage of Participants |