Clinical trial NCT04535037: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diphtheria
Keywords: Primary immunization
Immunogenicity
Safety
Diphtheria
Tetanus
Acellular pertussis
Hepatitis B
Inactivated poliovirus
Haemophilus influenzae type b
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2020-09-01
Enrollment: 500
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations at Month 11, Based on Per Protocol Set (PPS)
timeFrame: At Month 11 (i.e., 1-month post-booster vaccination)
measure: Percentage of Subjects With Anti-PRP Antibody Concentrations Equal to or Above (≥) 5 µg/mL at Month 11, Based on PPS
timeFrame: At Month 11 (i.e., 1-month post-booster vaccination)
measure: Anti-PRP Antibody Concentrations at Month 11, Based on the Exposed Set (ES)
timeFrame: At Month 11 (i.e., 1-month post-booster vaccination)
measure: Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 5 µg/mL at Month 11, Based on ES
timeFrame: At Month 11 (i.e., 1-month post-booster vaccination)
Secondary outcomes:
measure: Percentage of Subjects With Anti-PRP Antibody Concentration ≥ 0.15 µg/mL
timeFrame: 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)
measure: Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 1.0 µg/mL
timeFrame: 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)
measure: Anti-PRP Antibody Concentrations
timeFrame: 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)
measure: Number of Subjects With Unsolicited Adverse Events (AEs)
timeFrame: During the 31-day (Days 1-31) follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age)
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: Throughout the entire period of the study (from Day 1 up to study end [Month 11])
Other outcomes:
Locations:
city: Rosenheim
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Schoenau Am Koenigssee
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Wolfsburg
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Huerth
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Moenchengladbach
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Frankenthal
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Bramsche
country: Germany
facility: GSK Investigational Site
city: Erfurt
country: Germany
facility: GSK Investigational Site
city: Moenchengladbach
country: Germany
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Malaga
country: Spain
facility: GSK Investigational Site
state: Andalucia
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Boadilla Del Monte (Madrid)
country: Spain
facility: GSK Investigational Site
city: Leganes
country: Spain
facility: GSK Investigational Site
city: Lleida
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Santiago de Compostela
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Martinon-Torres F, Salamanca de la Cueva I, Horn M, Westerholt S, Bosis S, Meyer N, Cheuvart B, Virk N, Jakes RW, Duchenne M, Van den Steen P. Disparate kinetics in immune response of two different Haemophilus influenzae type b conjugate vaccines: Immunogenicity and safety observations from a randomized controlled phase IV study in healthy infants and toddlers using a 2+1 schedule. Hum Vaccin Immunother. 2024 Dec 31;20(1):2342630. doi: 10.1080/21645515.2024.2342630. Epub 2024 Apr 30.