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

NCT05289271 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: V419-0162021-004053-23
• Study Type: interventional
• Target: 168
• Locations: 3 countries
• Sites: 13

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™.

Conditions

Vaccines, Combined; Hexavalent Vaccine

Outcome Measures

Primary Outcomes (13)

• 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 Outcomes (2)

• Percentage of Participants With Pertactin (PRN) Vaccine Response

  30 days postvaccination (at ~12 months of age)

• Percentage of Participants With Fimbriae 2/3 (FIM 2/3) Vaccine Response

  30 days postvaccination (at ~12 months of age)

Study Arms (2)

Group 1: V, V, V

EXPERIMENTAL

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™

Group 2: H, H, V

EXPERIMENTAL

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™

Interventions

Vaxelis™ BIOLOGICAL

Vaxelis™ 0.5 mL sterile suspension in prefilled syringe for intramuscular administration.

Also known as: V419

Group 1: V, V, V; Group 2: H, H, V

Eligibility Criteria

• Age: 11 Months - 13 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (13)

Gemeinschaftspraxis Dres. Adelt, Mettlich-Lambrecht und Denneberg ( Site 0053)

Bramsche, Lower Saxony, 49565, Germany

Location

Kinderärztliche Gemeinschaftspraxis ( Site 0057)

Wolfsburg, Lower Saxony, 38448, Germany

Location

Kinder- und Jugendärzte Hürth-Park ( Site 0054)

Hürth, North Rhine-Westphalia, 50354, Germany

Location

Private Practice - Dr. Petri, Kinderarztpraxis ( Site 0056)

Hürth, North Rhine-Westphalia, 50354, Germany

Location

Gemeinschaftspraxis Matthias Donner & Dr. Martin Lüchtrath ( Site 0052)

Mönchengladbach, North Rhine-Westphalia, 41236, Germany

Location

Kinderärzte im Recker Park ( Site 0058)

Würselen, North Rhine-Westphalia, 52146, Germany

Location

A.O.U.C. Policlinico di Bari-Hygiene ( Site 0105)

Bari, Apulia, 70124, Italy

Location

A.O.U. Policlinico Paolo Giaccone ( Site 0102)

Palermo, Sicily, 90127, Italy

Location

CHUS - Hospital Clinico Universitario-Servicio de Pediatría ( Site 0001)

Santiago de Compostela, La Coruna, 15706, Spain

Location

Hospital Universitario La Paz-Pediatria y Enfermedades Infecciosas ( Site 0011)

Madrid, Madrid, Comunidad de, 28046, Spain

Location

Hospital Universitario HM Puerta del Sur-Pediatrics ( Site 0005)

Madrid, Madrid, Comunidad de, 28938, Spain

Location

Hospital Antequera-Pediatrics Unit ( Site 0004)

Antequera, Malaga, 29200, Spain

Location

Instituto Hispalense de Pediatria- IHP1 ( Site 0006)

Seville, Sevilla, 41014, Spain

Location

Related Publications (1)

• Guerra A, Costantino C, Martinon-Torres F, Westerholt S, Lambeth C, Chen Z, Lumley J, Marcek T, Johnson D, Wilck M. A phase 4, open-label study to evaluate the safety and immunogenicity of DTaP5-HBV-IPV-Hib in children previously vaccinated with DTaP2-HBV-IPV-Hib or DTaP5-HBV-IPV-Hib (V419-016). Hum Vaccin Immunother. 2024 Dec 31;20(1):2310900. doi: 10.1080/21645515.2024.2310900. Epub 2024 Feb 8.

  PMID: 38327239 RESULT

Related Links

• Merck Clinical Trials Information

MeSH Terms

Interventions

Vaxelis

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2022
• First Posted: March 21, 2022
• Study Start: March 25, 2022
• Primary Completion: August 30, 2022
• Study Completion: August 30, 2022
• Last Updated: July 29, 2024
• Results First Posted: September 6, 2023

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share

Locations

IT (2); ES (5); DE (6)