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)

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

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

Study Overview

• Status: Completed
• Conditions: Hepatitis B; Pertussis
• Intervention / Treatment: Other: Blood Sample

• Study Type: Interventional
• Enrollment (Actual): 754
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 5 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 1 (approximately 4 years after completion of the 3+1/2+1 schedule)
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.	Day 1 (approximately 4 years after completion of the 2+1 schedule)
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.	Day 1 (approximately 4 years after completion of the 2+1 schedule)
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.	Day 1 (approximately 4 years after completion of the 2+1 schedule)
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.	Day 1 (approximately 4 years after completion of the 2+1 schedule)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 1 (approximately 4 years after completion of the 3+1 or 2+1 schedule)
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.	Day 1 (approximately 4 years after completion of the 2+1 schedule)
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.	Day 1 (approximately 4 years after completion of the 2+1 schedule)
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.	Day 1 (approximately 4 years after completion of the 2+1 schedule)
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.	Day 1 (approximately 4 years after completion of the 2+1 schedule)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 4 days following blood sample on Day 1 (approximately 4 years after completion of the 3+1 or 2+1 schedule)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Vesikari T, Xu J, Johnson DR, Hall J, Marcek T, Goveia MG, Acosta CJ, Lee AW. Hepatitis B and pertussis antibodies in 4- to 5-year-old children previously vaccinated with different hexavalent vaccines. Hum Vaccin Immunother. 2020 Apr 2;16(4):867-874. doi: 10.1080/21645515.2019.1673119. Epub 2019 Nov 5.

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2016
• Primary Completion (Actual): July 29, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: April 29, 2016
• First Submitted That Met QC Criteria: April 29, 2016
• First Posted (Estimate): May 3, 2016

Study Record Updates

• Last Update Posted (Actual): June 9, 2020
• Last Update Submitted That Met QC Criteria: May 27, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Immune response
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Whooping Cough; Hepatitis; Hepatitis A
• Other Study ID Numbers: V419-012 (Other Identifier: Merck Protocol Number); 2016-000274-37 (Other Identifier: EudraCT Number); PRI03C (Other Identifier: MCMVaccBV Protocol ID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf