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

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.

Time frame: Up to 40 days postvaccination

Population: All participants who received study vaccination.

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.

Time frame: Up to 5 days postvaccination

Population: All participants who received study vaccination.

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.

Time frame: Up to 5 days postvaccination

Population: All participants who received study vaccination.

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.

Time frame: 30 days postvaccination (at ~12 months of age)

Population: All enrolled participants without deviations from the protocol that may substantially affect the results of the immunogenicity endpoint. Potential deviations include, but are not limited to failure to receive study vaccine at Visit 1 (Day 1); receipt of a prohibited medication or prohibited vaccine within the study window; or collection of blood sample at Visit 2 outside the prespecified window (Day 26 to Day 40).

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.

Time frame: 30 days postvaccination (at ~12 months of age)

Population: All enrolled participants without deviations from the protocol that may substantially affect the results of the immunogenicity endpoint. Potential deviations include, but are not limited to failure to receive study vaccine at Visit 1 (Day 1); receipt of a prohibited medication or prohibited vaccine within the study window; or collection of blood sample at Visit 2 outside the prespecified window (Day 26 to Day 40).

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.

Time frame: 30 days postvaccination (at ~12 months of age)

Population: All enrolled participants without deviations from the protocol that may substantially affect the results of the immunogenicity endpoint. Potential deviations include, but are not limited to failure to receive study vaccine at Visit 1 (Day 1); receipt of a prohibited medication or prohibited vaccine within the study window; or collection of blood sample at Visit 2 outside the prespecified window (Day 26 to Day 40).

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.

Time frame: 30 days postvaccination (at ~12 months of age)

Population: All enrolled participants without deviations from the protocol that may substantially affect the results of the immunogenicity endpoint. Potential deviations include, but are not limited to failure to receive study vaccine at Visit 1 (Day 1); receipt of a prohibited medication or prohibited vaccine within the study window; or collection of blood sample at Visit 2 outside the prespecified window (Day 26 to Day 40).

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.

Time frame: 30 days postvaccination (at ~12 months of age)

Population: All enrolled participants without deviations from the protocol that may substantially affect the results of the immunogenicity endpoint. Potential deviations include, but are not limited to failure to receive study vaccine at Visit 1 (Day 1); receipt of a prohibited medication or prohibited vaccine within the study window; or collection of blood sample at Visit 2 outside the prespecified window (Day 26 to Day 40).

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.

Time frame: 30 days postvaccination (at ~12 months of age)

Population: All enrolled participants without deviations from the protocol that may substantially affect the results of the immunogenicity endpoint. Potential deviations include, but are not limited to failure to receive study vaccine at Visit 1 (Day 1); receipt of a prohibited medication or prohibited vaccine within the study window; or collection of blood sample at Visit 2 outside the prespecified window (Day 26 to Day 40).

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.

Time frame: 30 days postvaccination (at ~12 months of age)

Population: All enrolled participants without deviations from the protocol that may substantially affect the results of the immunogenicity endpoint. Potential deviations include, but are not limited to failure to receive study vaccine at Visit 1 (Day 1); receipt of a prohibited medication or prohibited vaccine within the study window; or collection of blood sample at Visit 2 outside the prespecified window (Day 26 to Day 40).

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.

Time frame: 30 days postvaccination (at ~12 months of age)

Population: All enrolled participants without deviations from the protocol that may substantially affect the results of the immunogenicity endpoint. Potential deviations include, but are not limited to failure to receive study vaccine at Visit 1 (Day 1); receipt of a prohibited medication or prohibited vaccine within the study window; or collection of blood sample at Visit 2 outside the prespecified window (Day 26 to Day 40).

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.

Time frame: 30 days postvaccination (at ~12 months of age)

Population: All enrolled participants without deviations from the protocol that may substantially affect the results of the immunogenicity endpoint. Potential deviations include, but are not limited to failure to receive study vaccine at Visit 1 (Day 1); receipt of a prohibited medication or prohibited vaccine within the study window; or collection of blood sample at Visit 2 outside the prespecified window (Day 26 to Day 40).

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.

Time frame: Up to 15 days postvaccination

Population: All participants who received study vaccination.

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.

Time frame: 30 days postvaccination (at ~12 months of age)

Population: All enrolled participants without deviations from the protocol that may substantially affect the results of the immunogenicity endpoint. Potential deviations include, but are not limited to failure to receive study vaccine at Visit 1 (Day 1); receipt of a prohibited medication or prohibited vaccine within the study window; or collection of blood sample at Visit 2 outside the prespecified window (Day 26 to Day 40).

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.

Time frame: 30 days postvaccination (at ~12 months of age)

Population: All enrolled participants without deviations from the protocol that may substantially affect the results of the immunogenicity endpoint. Potential deviations include, but are not limited to failure to receive study vaccine at Visit 1 (Day 1); receipt of a prohibited medication or prohibited vaccine within the study window; or collection of blood sample at Visit 2 outside the prespecified window (Day 26 to Day 40).