Safety, Tolerability, and Immunogenicity of Vaxelis™ in Children Previously Vaccinated With Vaxelis™ or Hexyon™ (V419-016)

Phase 4

Completed

Conditions: Hexavalent Vaccine
Vaccines, Combined

Interventions: Biological: Vaxelis™

Registration Number: NCT05289271

Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary: The primary objectives of this study are to evaluate the safety, tolerability, and immunogenicity of a booster dose of Vaxelis™ (V419) given at \~11 to 13 months of age in healthy participants who were previously vaccinated with a 2-dose primary infant series of either Vaxelis™ or Hexyon™.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 168

Inclusion Criteria

Has received a 2-dose infant primary series of either Vaxelis™ or Hexyon™ at approximately 2 and 4 months of age

Exclusion Criteria

Has known or suspected impaired immunological function
Has known or history of functional or anatomic asplenia.
Has a known hypersensitivity to any component of the study vaccine.
Has a known or suspected blood dyscrasia, leukemia, lymphoma of any type or other malignant neoplasm affecting the hematopoietic and lymphatic system
Has a bleeding disorder contraindicating intramuscular vaccination
Has a history of Hib, hepatitis B, diphtheria, tetanus, pertussis, or poliovirus infection
Was born to a mother with a known history of hepatitis B infection
Had a recent febrile illness (defined as rectal temperature ≥38.1°C [≥100.5°F] or axillary temperature ≥37.8°C [≥100.0°F]) occurring at or within 72 hours prior to receipt of study vaccine
Has encephalopathy of unknown etiology, occurring within 7 days following prior vaccination with a pertussis containing vaccine
Has an uncontrolled neurologic disorder or uncontrolled epilepsy.
Has a health or developmental disorder that, based on the clinical judgment of the investigator, could affect evaluation of the vaccine
Has received or is expected to receive an immunosuppressive agent
Meets corticosteroid use criteria
Has received any licensed, non-live vaccine within 14 days of study vaccine
Has received any license live vaccine within 30 days of study vaccine
Has received a blood transfusion or blood product within 6 months of study vaccine

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: V, V, V	Vaxelis™	Participants who received a 2-dose regimen of Vaxelis™ as infants prior to enrollment will receive a Vaxelis™ booster at \~11 months of age.
Group 2: H, H, V	Vaxelis™	Participants who received a 2-dose regimen of Hexyon™ as infants prior to enrollment will receive a Vaxelis™ booster at \~11 months of age.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With a Solicited Injection-site Adverse Event (AE)	Up to 5 days postvaccination	Solicited injection-site AEs are predefined local (at the injection/administration site) events for which the participant's legally authorized representative was specifically questioned. Participant's legally acceptable representative used a Vaccination Report Card (VRC) to report the following solicited injection-site AEs : swelling, redness (erythema), and pain/tenderness. 95% confidence intervals (CIs) were calculated based on the exact binomial method proposed by Clopper and Pearson.
Percentage of Participants With Diphtheria Toxoid Antibodies ≥0.1 IU/mL	30 days postvaccination (at ~12 months of age)	Human antibodies to diphtheria toxoid were quantified using the Meso Scale Discovery Electrochemiluminescence serological assay based on an established reference standard sample curve with the lower limit of quantitation (LLOQ) for diphtheria antibody of 0.005 IU/mL. The percentage of participants with diphtheria toxoid antibodies ≥0.1 international units per milliliter (IU/mL) one month after Vaxelis™ as the 3rd dose of a vaccination series is presented. The 95% CIs are based on the exact binomial method proposed by Clopper and Pearson.
Percentage of Participants With Pertussis Toxoid (PT) Vaccine Response	30 days postvaccination (at ~12 months of age)	Human antibodies to pertussis toxoid were quantified using the Meso Scale Discovery Electrochemiluminescence serological assay based on an established reference standard sample curve with a LLOQ for pertussis antibody of 2.00 EU/mL. The percentage of participants meeting response criteria for PT is based on pre-vaccination level of PT is presented. The 95% CIs are based on the exact binomial method proposed by Clopper and Pearson.
Percentage of Participants With a Solicited Systemic AE	Up to 5 days postvaccination	Solicited systemic AE are predefined systemic events for which the participant's legally authorized representative was specifically questioned. Participant's legally acceptable representative used a VRC to report the following solicited systemic AEs: vomiting, drowsiness (somnolence), loss of appetite, and irritability. 95% CIs were calculated based on the exact binomial method proposed by Clopper and Pearson.
Percentage of Participants With Unsolicited AEs	Up to 15 days postvaccination	An unsolicited AE is an AE that was not solicited using a VRC and that is communicated by a participant's legally authorized representative who has signed the informed consent. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. 95% CIs were calculated based on the exact binomial method proposed by Clopper and Pearson.
Percentage of Participants With Tetanus Toxoid Antibodies ≥0.1 IU/mL	30 days postvaccination (at ~12 months of age)	Human antibodies to tetanus toxoid were quantified using the Meso Scale Discovery Electrochemiluminescence serological assay based on an established reference standard sample curve with a LLOQ for tetanus antibody of 0.01 IU/mL. The percentage of participants with tetanus toxoid antibodies ≥0.1 IU/mL one month after Vaxelis™ as the 3rd dose of a vaccination series is presented. The 95% CIs are based on the exact binomial method proposed by Clopper and Pearson.
Percentage of Participants With Haemophilus Influenzae Type b Polyribosylribitol Phosphate (Hib-PRP) Antibodies ≥1.0 µg/mL	30 days postvaccination (at ~12 months of age)	Human antibodies to Hib-PRP were quantified using the Vacczyme™ Human Anti-Haemophilus influenzae Type b Enzyme Immunoassay Kit. Levels of anti-Hib IgG were quantified by interpolation from a standard curve that has been calibrated to the FDA lot 1983 reference serum. The percentage of participants with Hib-PRP antibodies ≥0.1 IU/mL one month after Vaxelis™ as the 3rd dose of a vaccination series is presented. The 95% CIs are based on the exact binomial method proposed by Clopper and Pearson.
Percentage of Participants With Poliovirus Serotype 1 Neutralizing Antibodies (Nab) ≥1:8 Dilution	30 days postvaccination (at ~12 months of age)	Human antibodies to poliovirus serotype 1 were quantified with a neutralization assay by utilizing Vero cells and wild type poliovirus strain 1 as the challenge virus. The Karber method was used to determine the serum dilution that neutralized 50% of the challenge virus, with results expressed as titers (1:dilution), and the LLOQ was 1:4. dilution. The percentage of participants with poliovirus serotype 1 Nab ≥1:8 dilution one month after Vaxelis™ as the 3rd dose of a vaccination series is presented. The 95% CIs are based on the exact binomial method proposed by Clopper and Pearson.
Percentage of Participants With a Serious AE (SAE)	Up to 40 days postvaccination	An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. 95% CIs were calculated based on the exact binomial method proposed by Clopper and Pearson.
Percentage of Participants With Filamentous Hemagglutinin (FHA) Vaccine Response	30 days postvaccination (at ~12 months of age)	Human antibodies to FHA were quantified using the Meso Scale Discovery Electrochemiluminescence serological assay based on an established reference standard sample curve with a LLOQ for FHA antibody of 2.00 EU/mL. The percentage of participants meeting response criteria for FHA response will be based on pre-vaccination level of FHA. The 95% CIs are based on the exact binomial method proposed by Clopper and Pearson.
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Antibodies ≥10 mIU/mL	30 days postvaccination (at ~12 months of age)	Human antibodies to HBsAg were quantified using an Enhanced Chemiluminescence (ECi) assay, with the hepatitis B WHO International reference standard at 10 mIU/mL as a control in every assay, and the LLOQ of the assay is 5 mIU/mL. The percentage of participants with HBsAg antibodies ≥10 milli-international per liter (mIU/mL) one month after Vaxelis™ as the 3rd dose of a vaccination series is presented. The 95% CIs are based on the exact binomial method proposed by Clopper and Pearson.
Percentage of Participants With Poliovirus Serotype 2 Neutralizing Antibodies (Nab) ≥1:8 Dilution	30 days postvaccination (at ~12 months of age)	Human antibodies to poliovirus serotype 2 were quantified with a neutralization assay by utilizing Vero cells and wild type poliovirus strain 2 as the challenge virus. The Karber method was used to determine the serum dilution that neutralized 50% of the challenge virus, with results expressed as titers (1:dilution), and the LLOQ was 1:4. dilution. The percentage of participants with poliovirus serotype 2 Nab ≥1:8 dilution one month after Vaxelis™ as the 3rd dose of a vaccination series is presented. The 95% CIs are based on the exact binomial method proposed by Clopper and Pearson.
Percentage of Participants With Poliovirus Serotype 3 Neutralizing Antibodies (Nab) ≥1:8 Dilution	30 days postvaccination (at ~12 months of age)	Human antibodies to poliovirus serotype 3 were quantified with a neutralization assay by utilizing Vero cells and wild type poliovirus strain 3 as the challenge virus. The Karber method was used to determine the serum dilution that neutralized 50% of the challenge virus, with results expressed as titers (1:dilution), and the LLOQ was 1:4. dilution. The percentage of participants with poliovirus serotype 3 Nab ≥1:8 dilution one month after Vaxelis™ as the 3rd dose of a vaccination series is presented. The 95% CIs are based on the exact binomial method proposed by Clopper and Pearson.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Fimbriae 2/3 (FIM 2/3) Vaccine Response	30 days postvaccination (at ~12 months of age)	Human antibodies to FIM 2/3 were quantified using the Meso Scale Discovery Electrochemiluminescence serological assay based on an established reference standard sample curve with a LLOQ for pertussis antibody of 2.00 EU/mL. The percentage of participants meeting response criteria for FIM 2/3 was based on pre-vaccination level of FIM 2/3. The 95% CIs are based on the exact binomial method proposed by Clopper and Pearson.
Percentage of Participants With Pertactin (PRN) Vaccine Response	30 days postvaccination (at ~12 months of age)	Human antibodies to PRN were quantified using the Meso Scale Discovery Electrochemiluminescence serological assay based on an established reference standard sample curve with a LLOQ for PRN of 2.00 EU/mL.The percentage of participants meeting response criteria for PRN was based on pre-vaccination level of PRN. The 95% CIs are based on the exact binomial method proposed by Clopper and Pearson.

Trial Locations

Locations (13): Private Practice - Dr. Petri, Kinderarztpraxis ( Site 0056)
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Huerth, Nordrhein-Westfalen, Germany
Gemeinschaftspraxis Dres. Adelt, Mettlich-Lambrecht und Denneberg ( Site 0053)
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Bramsche, Niedersachsen, Germany
Kinderärztliche Gemeinschaftspraxis ( Site 0057)
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Wolfsburg, Niedersachsen, Germany
Kinder- und Jugendärzte Hürth-Park ( Site 0054)
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Hürth, Nordrhein-Westfalen, Germany
Gemeinschaftspraxis Matthias Donner & Dr. Martin Lüchtrath ( Site 0052)
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Mönchengladbach, Nordrhein-Westfalen, Germany
A.O.U.C. Policlinico di Bari-Hygiene ( Site 0105)
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Bari, Puglia, Italy
Kinderärzte im Recker Park ( Site 0058)
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Würselen, Nordrhein-Westfalen, Germany
A.O.U. Policlinico Paolo Giaccone ( Site 0102)
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Palermo, Sicilia, Italy
CHUS - Hospital Clinico Universitario-Servicio de Pediatría ( Site 0001)
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Santiago de Compostela, La Coruna, Spain
Hospital Universitario La Paz-Pediatria y Enfermedades Infecciosas ( Site 0011)
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Madrid, Madrid, Comunidad De, Spain
Hospital Universitario HM Puerta del Sur-Pediatrics ( Site 0005)
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Madrid, Madrid, Comunidad De, Spain
Hospital Antequera-Pediatrics Unit ( Site 0004)
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Antequera, Malaga, Spain
Instituto Hispalense de Pediatria- IHP1 ( Site 0006)
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Seville, Sevilla, Spain