A Study to Evaluate Immunogenicity and Safety of GlaxoSmithKline (GSK)'s Infanrix Hexa Vaccine (DTPa-HBV-IPV/Hib) Versus MCM Vaccine BV's Vaxelis Vaccine (DTaP5-HBV-IPV-Hib) in Healthy Infants and Toddlers

A Phase IV, Single-blind, Randomised, Controlled, Multi-country Study to Evaluate the Immunogenicity and Safety of GSK's Infanrix Hexa (DTPa-HBV-IPV/Hib) Versus MCM Vaccine BV's Vaxelis (DTaP5-HBV-IPV Hib), When Administered Intramuscularly According to a 2-, 4- and 12-month Schedule in Healthy Infants and Toddlers

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.

Study Overview

• Status: Completed
• Conditions: Diphtheria
• Intervention / Treatment: Biological: DTPa-HBV-IPV/Hib; Biological: Pneumococcal 13-valent conjugate vaccine; Biological: DTaP5-HBV-IPV-Hib

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Bramsche, Germany, 49565
    • GSK Investigational Site
  • Erfurt, Germany, 99086
    • GSK Investigational Site
  • Moenchengladbach, Germany, 41236
    • GSK Investigational Site
  • Bayern
    • Rosenheim, Bayern, Germany, 83026
      • GSK Investigational Site
    • Schoenau Am Koenigssee, Bayern, Germany, 83471
      • GSK Investigational Site
  • Brandenburg
    • Leipzig, Brandenburg, Germany, 16269
      • GSK Investigational Site
  • Niedersachsen
    • Wolfsburg, Niedersachsen, Germany, 38448
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Huerth, Nordrhein-Westfalen, Germany, 50354
      • GSK Investigational Site
    • Moenchengladbach, Nordrhein-Westfalen, Germany, 41236
      • GSK Investigational Site
  • Rheinland-Pfalz
    • Frankenthal, Rheinland-Pfalz, Germany, 67227
      • GSK Investigational Site
• Italy
  • Milano, Italy, 20122
    • GSK Investigational Site
• Spain
  • Badalona, Spain, 08916
    • GSK Investigational Site
  • Boadilla Del Monte (Madrid), Spain, 28660
    • GSK Investigational Site
  • Leganes, Spain, 28911
    • GSK Investigational Site
  • Lleida, Spain, 25198
    • GSK Investigational Site
  • Madrid, Spain, 28040
    • GSK Investigational Site
  • Madrid, Spain, 28046
    • GSK Investigational Site
  • Santiago de Compostela, Spain, 15706
    • GSK Investigational Site
  • Sevilla, Spain, 41013
    • GSK Investigational Site
  • Andalucia
    • Malaga, Andalucia, Spain, 29004
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: DTPa-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; Other Names: Infanrix hexa; Biological: Pneumococcal 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; Other Names: Prevenar 13
Active Comparator: 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.	Biological: Pneumococcal 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; Other Names: Prevenar 13; Biological: DTaP5-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; Other Names: Vaxelis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	At Month 11 (i.e., 1-month post-booster vaccination)
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.	At Month 11 (i.e., 1-month post-booster vaccination)
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.	At Month 11 (i.e., 1-month post-booster vaccination)
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.	At Month 11 (i.e., 1-month post-booster vaccination)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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)
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.	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	Anti-PRP antibody concentrations were presented as GMCs and expressed in μg/mL, as assessed by ELISA.	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)
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.	During the 31-day (Days 1-31) follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age)
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.	Throughout the entire period of the study (from Day 1 up to study end [Month 11])

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2021
• Primary Completion (Actual): July 25, 2022
• Study Completion (Actual): July 25, 2022

Study Registration Dates

• First Submitted: August 27, 2020
• First Submitted That Met QC Criteria: August 27, 2020
• First Posted (Actual): September 1, 2020

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Hepatitis B; Primary immunization; Diphtheria; Tetanus; Haemophilus influenzae type b; Acellular pertussis; Inactivated poliovirus
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Corynebacterium Infections; Diphtheria; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 212645; 2019-002988-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No