Immunogenicity of the 9vHPV Vaccination 2-dose Regimen Among Children 4 to 8 Years Old, An Exploratory Immunogenicity Study

An Open-Label Clinical Trial Evaluating the Immunogenicity of the 9vHPV Vaccination 2-dose Regimen Over a Four-year Follow up Among Children 4 to 8 Years Old, An Exploratory Immunogenicity Study

This study is an open-label nonrandomized exploratory proof of concept and descriptive 4-year immunogenicity study to assess immunogenicity after administration of a 2-dose regimen of 9-valent human papillomavirus vaccine (9vHPV) vaccine separated by 12 months (months 0, 12).

Study Overview

• Status: Recruiting
• Conditions: Human Papilloma Virus
• Intervention / Treatment: Drug: Gardasil9

Detailed Description

Study participants will include 150 boys and girls aged 4-8 years (total, 75 boys and 75 girls) to receive 2 doses of the 9vHPV vaccine at 0 and 12 months. Patients will be recruited by age-group to achieve balanced enrollment of 15 girls and 15 boys per year of age. The investigators will examine the immunogenicity profile in this cohort, for which titers will be analyzed one month after dose 2 (Month 13) and at Month 60.

Though clinical efficacy cannot be assessed in young children because of limited exposure to human papillomavirus (HPV), this descriptive study will allow the investigators to understand whether the 9vHPV vaccine in younger patients provides immunogenicity similar to that shown for the 9-14 and 16-26 age groups who have received the 9vHPV vaccine.13 This study will require an IND for the use of the HPV vaccine in children younger than 9 years.

Immunogenicity will be measured by examining serum antibodies of all participants using a competitive Luminex immunoassay (cLIA).15 Month 60 serology will be by cLIA and IgG LIA assays. The antibody response testing will be performed at Merck Research Laboratory.

The goal of this study is to explore whether a 2-dose 9vHPV vaccine regimen with dosage separated by 12 months is immunogenic among children aged 4-8 years. The primary outcome will be geometric mean titers (GMT) for HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, HPV45, HPV52, and HPV58 antibodies at months 13 and 60. Results will allow the investigators to qualitatively compare immunogenicity in individuals vaccinated at age 4-8 years to known immunogenicity in 9vHPV recipients vaccinated at ages 9-14.13 Knowledge of whether vaccination in this age group is sufficient to induce high-level protective antibody titers through 4 years after the second dose will support further efficacy studies in a larger randomized trial of a 2-dose 9vHPV regimen for children aged 4-8 years.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Natalie Pierre-Joseph, MD; Phone Number: 781-879-4841; Email: napierre@bu.edu
• Study Contact Backup: Name: Johane Seide, MBA; Phone Number: 617-414-5528; Email: johane.seide@bmc.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Recruiting
      • Boston Medical Center
      • Contact: Natalie Pierre-Joseph, MD; Phone Number: 781-879-4841; Email: napierre@bu.edu
      • Contact: Johane Seide, MBA; Phone Number: 617-414-5528; Email: johane.seide@bmc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 8 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Children aged 4-8 years old
2. Receives care at the Boston Medical Center or one of the affiliated Community heath centers
3. Naïve to HPV Vaccine

Exclusion Criteria:

1. A history of severe allergic reaction, including known allergy to any vaccine component, specially severe allergic reaction to yeast
2. Immunocompromised/previous immunosuppressive therapy
3. Thrombocytopenia or other coagulation disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm; HPV 9-valent human papillomavirus vaccine (Gardasil 9) - 0.5mL intramuscular dose - 2 doses (Month 0, 12)	Drug: Gardasil9; The Gardasil 9 vaccine is a recombinant L 1 VLP vaccine containing HPV types 6, 11,16,18, 31, 33, 45, 52 and 58 VLP. The vaccine is not currently licensed for children under 9 years of age but it is licensed in the USA for males and females ages 9 to 45 years old.; Other Names: GARDASIL®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HPV6 antibodies at 13 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV6 if it is >30mMu.	13 months
HPV11 antibodies at 13 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV11 if it is >16mMu.	13 months
HPV16 antibodies at 13 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV16 if it is >20mMu.	13 months
HPV18 antibodies at 13 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV18 if it is >24 mMU.	13 months
HPV31 antibodies at 13 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV31 if it is >10 mMU.	13 months
HPV33 antibodies at 13 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV33 if it is >8 mMU.	13 months
HPV45 antibodies at 13 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV45 if it is >8 mMU.	13 months
HPV52 antibodies at 13 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV52 if it is >8 mMU.	13 months
HPV58 antibodies at 13 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV58 if it is >8 mMU.	13 months
HPV6 antibodies at 60 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV6 if it is >30mMU.	60 months
HPV11 antibodies at 60 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV11 if it is >16 mMU.	60 months
HPV16 antibodies at 60 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV16 if it is >20 mMU.	60 months
HPV18 antibodies at 60 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV18 if it is >24mMU.	60 months
HPV31 antibodies at 60 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV31 if it is >10 mMU.	60 months
HPV33 antibodies at 60 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV33 if it is >8 mMU.	60 months
HPV45 antibodies at 60 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV45 if it is >8 mMU.	60 months
HPV52 antibodies at 60 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV52 if it is >8 mMU.	60 months
HPV58 antibodies at 60 months	A serum sample will be analyzed using 9-valent Luminex immunoassay (cLIA, mMU/mL) to assess the geometric mean for HPV antibodies. The results will be considered positive for HPV58 if it is >8 mMU.	60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Injection site swelling after first injection	Solicited local swelling will be graded from 0-4 where 0 is no swelling and 4 is severe swelling.	day 3 after injection
Injection site swelling after second injection	Solicited local swelling will be graded from 0-4 where 0 is no swelling and 4 is severe swelling.	day 3 after injection
Injection site redness after first injection	Solicited local redness will be graded from 0-4 where 0 is no redness and 4 is severe redness.	day 3 after injection
Injection site redness after second injection	Solicited local redness will be graded from 0-4 where 0 is no redness and 4 is severe redness.	day 3 after injection

Collaborators and Investigators

• Sponsor: Boston Medical Center
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Natalie Pierre-Joseph, MD, Boston Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2022
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 21, 2022
• First Submitted That Met QC Criteria: April 12, 2022
• First Posted (Actual): April 15, 2022

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Children; Immunogenicity; Gardasil 9
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Papilloma
• Other Study ID Numbers: H-41686

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes