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 (V419-012)

• Sponsor: MCM Vaccines B.V. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02759354
• Collaborator: Merck Sharp & Dohme LLC (Industry), Sanofi Pasteur, a Sanofi Company (Industry)
• Enrollment: 754
• Arms: 4
• Actual Duration (Months): 3.2

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B; Pertussis	Other: Blood Sample	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 754 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Long-term Persistence of Hepatitis B and Pertussis Antibody Responses in Healthy 4 to 5 Year-Old Children Previously Vaccinated With a 2-Dose or 3-Dose Infants Series and Toddler Dose With Vaxelis® or INFANRIX® Hexa
• Actual Study Start Date: Apr 26, 2016
• Actual Primary Completion Date: Jul 29, 2016
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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).	Other: Blood Sample; Blood sample at approx. 4 years of age; Other Names: Vaxelis® INFANRIX® hexa
Active Comparator: 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).	Other: Blood Sample; Blood sample at approx. 4 years of age; Other Names: Vaxelis® INFANRIX® hexa
Experimental: 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).	Other: Blood Sample; Blood sample at approx. 4 years of age; Other Names: Vaxelis® INFANRIX® hexa
Active Comparator: 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).	Other: Blood Sample; Blood sample at approx. 4 years of age; Other Names: Vaxelis® INFANRIX® hexa

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Secondary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Other Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 5 Years
• Sexes Eligible for Study: All
• Accepts 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 exclusion criteria. If a participant meets criteria 5 and/or 6 at the time of Visit 1, a further appointment is to be scheduled to reassess the participant's eligibility.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• MCM Vaccines B.V.
• Merck Sharp & Dohme LLC
• Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: MCM Vaccines B.V.
• ClinicalTrials.gov Identifier: NCT02759354
• Other Study ID Numbers: V419-012; 2016-000274-37; PRI03C; V419-012
• First Posted: May 3, 2016
• Last Update Posted: Jun 9, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by MCM Vaccines B.V.: Immune response
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Whooping Cough; Hepatitis

Study Results

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 Detail	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.

Arm/Group Title	Group Vaxelis (3+1)	Group Infanrix Hexa (3+1)	Group Vaxelis (2+1)	Group Infanrix Hexa (2+1)
Arm/Group Description	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.	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.	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.	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.
Period Title: Overall Study
STARTED	192	190	181	191
COMPLETED	192	190	181	191
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Group Vaxelis (3+1)	Group Infanrix Hexa (3+1)	Group Vaxelis (2+1)	Group Infanrix Hexa (2+1)	Total
Arm/Group Description	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.	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.	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.	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.	Total of all reporting groups
Overall Participants	191	189	181	191	752
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	4.8 (0.2)	4.8 (0.2)	3.9 (0.1)	3.9 (0.1)	4.4 (0.4)
Sex: Female, Male (Count of Participants)
Female	98 51.3%	86 45.5%	84 46.4%	94 49.2%	362 48.1%
Male	93 48.7%	103 54.5%	97 53.6%	97 50.8%	390 51.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Responding to Hepatitis B Surface Antigen (HBsAg)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Group Vaxelis (3+1)	Group Infanrix Hexa (3+1)	Group Vaxelis (2+1)	Group Infanrix Hexa (2+1)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	191	189	181	190
Number (95% Confidence Interval) [Percentage of Participants]	70.16 36.7%	82.01 43.4%	65.75 36.3%	83.68 43.8%

2. Secondary Outcome

Title	Geometric Mean Concentration of Antibodies to HBsAg
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Group Vaxelis (3+1)	Group Infanrix Hexa (3+1)	Group Vaxelis (2+1)	Group Infanrix Hexa (2+1)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	191	189	181	190
Geometric Mean (95% Confidence Interval) [mIU/mL]	24.43	51.30	19.44	71.00

3. Secondary Outcome

Title	Geometric Mean Concentration of Antibodies to Pertussis Toxin
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Group Vaxelis (2+1)	Group Infanrix Hexa (2+1)
Arm/Group Description	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.	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.
Measure Participants	178	188
Geometric Mean (95% Confidence Interval) [EU/mL]	5.31	3.64

4. Primary Outcome

Title	Percentage of Participants Responding to Pertussis Toxin
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Group Vaxelis (2+1)	Group Infanrix Hexa (2+1)
Arm/Group Description	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.	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.
Measure Participants	178	188
Concentration ≥LLOQ	58.43 30.6%	41.49 22%
Concentration ≥2×LLOQ	40.45 21.2%	21.81 11.5%
Concentration ≥4×LLOQ	14.61 7.6%	3.72 2%

5. Primary Outcome

Title	Percentage of Participants Responding to Pertussis Filamentous Hemagglutinin
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Group Vaxelis (2+1)	Group Infanrix Hexa (2+1)
Arm/Group Description	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.	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.
Measure Participants	173	188
Concentration ≥LLOQ	80.92 42.4%	88.30 46.7%
Concentration ≥2×LLOQ	46.82 24.5%	70.74 37.4%
Concentration ≥4×LLOQ	26.01 13.6%	45.21 23.9%

6. Primary Outcome

Title	Percentage of Participants Responding to Pertussis Pertactin
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Group Vaxelis (2+1)	Group Infanrix Hexa (2+1)
Arm/Group Description	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.	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.
Measure Participants	180	190
Concentration ≥LLOQ	66.11 34.6%	72.63 38.4%
Concentration ≥2×LLOQ	43.89 23%	51.05 27%
Concentration ≥4×LLOQ	15.56 8.1%	18.42 9.7%

7. Primary Outcome

Title	Percentage of Participants Responding to Pertussis Fimbriae
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Group Vaxelis (2+1)	Group Infanrix Hexa (2+1)
Arm/Group Description	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.	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.
Measure Participants	177	183
Concentration ≥LLOQ	94.35 49.4%	3.28 1.7%
Concentration ≥2×LLOQ	88.14 46.1%	2.19 1.2%
Concentration ≥4×LLOQ	69.49 36.4%	1.09 0.6%

8. Secondary Outcome

Title	Geometric Mean Concentration of Antibodies to Pertussis Filamentous Hemagglutinin
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Group Vaxelis (2+1)	Group Infanrix Hexa (2+1)
Arm/Group Description	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.	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.
Measure Participants	173	188
Geometric Mean (95% Confidence Interval) [EU/mL]	6.62	11.05

9. Secondary Outcome

Title	Geometric Mean Concentration of Antibodies to Pertussis Pertactin
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Group Vaxelis (2+1)	Group Infanrix Hexa (2+1)
Arm/Group Description	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.	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.
Measure Participants	180	190
Geometric Mean (95% Confidence Interval) [EU/mL]	5.94	7.19

10. Secondary Outcome

Title	Geometric Mean Concentration of Antibodies to Pertussis Fimbriae
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Group Vaxelis (2+1)	Group Infanrix Hexa (2+1)
Arm/Group Description	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.	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.
Measure Participants	177	183
Geometric Mean (95% Confidence Interval) [EU/mL]	25.99	2.13

11. Other Pre-specified Outcome

Title	Percentage of Participants With One or More Serious Adverse Events Related to Study Procedure
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Group Vaxelis (3+1)	Group Infanrix Hexa (3+1)	Group Vaxelis (2+1)	Group Infanrix Hexa (2+1)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	191	189	181	191
Number [Percentage of Participants]	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	Up to 4 days after Day 1
Adverse Event Reporting Description	Adverse Events (AE) are reported for the Persistence Analysis Set which included all participants previously vaccinated in studies V419-007 or V419-008 with immunogenicity results available. Vaccine safety was not assessed in this study.
Arm/Group Title	Group Vaxelis (3+1)		Group Infanrix Hexa (3+1)		Group Vaxelis (2+1)		Group Infanrix Hexa (2+1)
Arm/Group Description	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.		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.		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.		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.
All Cause Mortality
	Group Vaxelis (3+1)		Group Infanrix Hexa (3+1)		Group Vaxelis (2+1)		Group Infanrix Hexa (2+1)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Group Vaxelis (3+1)		Group Infanrix Hexa (3+1)		Group Vaxelis (2+1)		Group Infanrix Hexa (2+1)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/191 (0%)		0/189 (0%)		0/181 (0%)		0/191 (0%)
Other (Not Including Serious) Adverse Events
	Group Vaxelis (3+1)		Group Infanrix Hexa (3+1)		Group Vaxelis (2+1)		Group Infanrix Hexa (2+1)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/191 (0%)		0/189 (0%)		0/181 (0%)		0/191 (0%)

Limitations/Caveats

Vaccine safety was not assessed in the present study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations based on these study results 60 calendar days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential will be deleted prior to submission. Whenever needed, Sponsor review may be shorter upon agreement between the Sponsor and the authors.