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

Study Overview
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Brief Summary
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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™.

Official Title
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A Phase 4, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, and Immunogenicity of Vaxelis™ in Healthy Children Previously Vaccinated With a 2-Dose Primary Infant Series of Either Vaxelis™ or Hexyon™

Conditions
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Vaccines, Combined, Hexavalent Vaccine

Intervention / Treatment
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* Biological: Vaxelis™


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 11 Months
Maximum Age: 13 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: V, V, V<br>Participants who received a 2-dose regimen of Vaxelis™ as infants prior to enrollment will receive a Vaxelis™ booster at  11 months of age. | Biological: Vaxelis™<br>* Vaxelis™ 0.5 mL sterile suspension in prefilled syringe for intramuscular administration.<br>* Other names: V419;|
| Experimental: Group 2: H, H, V<br>Participants who received a 2-dose regimen of Hexyon™ as infants prior to enrollment will receive a Vaxelis™ booster at  11 months of age. | Biological: Vaxelis™<br>* Vaxelis™ 0.5 mL sterile suspension in prefilled syringe for intramuscular administration.<br>* Other names: V419;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Solicited Injection-site Adverse Event (AE) | 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. | Up to 5 days postvaccination | 
| Percentage of Participants With a Solicited Systemic AE | 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. | Up to 5 days postvaccination | 
| Percentage of Participants With Unsolicited AEs | 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. | Up to 15 days postvaccination | 
| Percentage of Participants With a Serious AE (SAE) | 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. | Up to 40 days postvaccination | 
| Percentage of Participants With Diphtheria Toxoid Antibodies ≥0.1 IU/mL | 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. | 30 days postvaccination (at  12 months of age) | 
| Percentage of Participants With Tetanus Toxoid Antibodies ≥0.1 IU/mL | 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. | 30 days postvaccination (at  12 months of age) | 
| Percentage of Participants With Pertussis Toxoid (PT) Vaccine Response | 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. | 30 days postvaccination (at  12 months of age) | 
| Percentage of Participants With Filamentous Hemagglutinin (FHA) Vaccine Response | 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. | 30 days postvaccination (at  12 months of age) | 
| Percentage of Participants With Haemophilus Influenzae Type b Polyribosylribitol Phosphate (Hib-PRP) Antibodies ≥1.0 µg/mL | 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. | 30 days postvaccination (at  12 months of age) | 
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Antibodies ≥10 mIU/mL | 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. | 30 days postvaccination (at  12 months of age) | 
| Percentage of Participants With Poliovirus Serotype 1 Neutralizing Antibodies (Nab) ≥1:8 Dilution | 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. | 30 days postvaccination (at  12 months of age) | 
| Percentage of Participants With Poliovirus Serotype 2 Neutralizing Antibodies (Nab) ≥1:8 Dilution | 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. | 30 days postvaccination (at  12 months of age) | 
| Percentage of Participants With Poliovirus Serotype 3 Neutralizing Antibodies (Nab) ≥1:8 Dilution | 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. | 30 days postvaccination (at  12 months of age) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Pertactin (PRN) Vaccine Response | 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. | 30 days postvaccination (at  12 months of age) | 
| Percentage of Participants With Fimbriae 2/3 (FIM 2/3) Vaccine Response | 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. | 30 days postvaccination (at  12 months of age) |