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

• DTPa-HBV-IPV/Hib (Biological), also known as Infanrix hexa: 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
• DTaP5-HBV-IPV-Hib (Biological), also known as Vaxelis: 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
• Pneumococcal 13-valent conjugate vaccine (Biological), also known as Prevenar 13: 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

Primary outcomes

• Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations at Month 11, Based on Per Protocol Set (PPS) [At Month 11 (i.e., 1-month post-booster vaccination)]: 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).
• Percentage of Subjects With Anti-PRP Antibody Concentrations Equal to or Above (≥) 5 µg/mL at Month 11, Based on PPS [At Month 11 (i.e., 1-month post-booster vaccination)]: The percentage of subjects with anti-PRP antibody concentrations ≥5 µg/mL was reported, as assessed by ELISA.
• Anti-PRP Antibody Concentrations at Month 11, Based on the Exposed Set (ES) [At Month 11 (i.e., 1-month post-booster vaccination)]: Anti-PRP antibody concentrations were presented as GMCs and expressed in μg/mL, as assessed by ELISA.
• Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 5 µg/mL at Month 11, Based on ES [At Month 11 (i.e., 1-month post-booster vaccination)]: The percentage of subjects with anti-PRP antibody concentrations ≥5 µg/mL was reported, as assessed by ELISA.

Secondary outcomes

• Percentage of Subjects With Anti-PRP Antibody Concentration ≥ 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)]: 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.
• Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 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)]: 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.
• Anti-PRP Antibody Concentrations [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 were presented as GMCs and expressed in μg/mL, as assessed by ELISA.
• Number of Subjects With Unsolicited Adverse Events (AEs) [During the 31-day (Days 1-31) follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age)]: 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.
• Number of Subjects With Serious Adverse Events (SAEs) [Throughout the entire period of the study (from Day 1 up to study end [Month 11])]: 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.

Sex: All, ages: 6 Weeks to 12 Weeks, accepts healthy volunteers

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.

Participant flow

Outcome results

• Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations at Month 11, Based on Per Protocol Set (PPS) (Primary), Geometric mean, μg/mL: Infanrix Hexa 11.61 (NA to NA); Vaxelis 12.66 (NA to NA)
• Percentage of Subjects With Anti-PRP Antibody Concentrations Equal to or Above (≥) 5 µg/mL at Month 11, Based on PPS (Primary), Number, Percentage of Participants: Infanrix Hexa 75.4; Vaxelis 81.7
• Anti-PRP Antibody Concentrations at Month 11, Based on the Exposed Set (ES) (Primary), Geometric mean, μg/mL: Infanrix Hexa 11.26 (NA to NA); Vaxelis 12.85 (NA to NA)
• Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 5 µg/mL at Month 11, Based on ES (Primary), Number, Percentage of Participants: Infanrix Hexa 75.4; Vaxelis 81.6
• Percentage of Subjects With Anti-PRP Antibody Concentration ≥ 0.15 µg/mL (Secondary), Number, Percentage of Participants: Infanrix Hexa 79.8 (73.79 to 84.99); Vaxelis 100 (98.41 to 100)
• Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 1.0 µg/mL (Secondary), Number, Percentage of Participants: Infanrix Hexa 30.5 (24.41 to 37.18); Vaxelis 92.2 (87.91 to 95.30)
• Anti-PRP Antibody Concentrations (Secondary), Geometric mean, μg/mL: Infanrix Hexa 0.5 (0.41 to 0.62); Vaxelis 11.3 (9.35 to 13.60)
• Number of Subjects With Unsolicited Adverse Events (AEs) (Secondary), Count of participants, Participants: Infanrix Hexa 178; Vaxelis 199
• Number of Subjects With Serious Adverse Events (SAEs) (Secondary), Count of participants, Participants: Infanrix Hexa 14; Vaxelis 10

Adverse events

Time frame: Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).

Serious adverse events by term

Other adverse events by term

105 more terms not shown.

• 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. PMID 38687024

• Study Protocol (PDF, 2021-04-06)
• Statistical Analysis Plan (PDF, 2021-01-07)

• GSK Clinical Trials, Study director, GlaxoSmithKline

NIH grants: 2019