An Exploratory Open-Label Clinical Trial Evaluating the Immunogenicity of the 9-valent 2-dose HPV Vaccination Regimen

Study Overview
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Brief Summary
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The goal of this study is to explore and evaluate whether a 2-dose schedule of Gardasil 9 among young and mid-adult women 16-45 years of age is generally safe and immunogenic, with an antibody response that is not inferior to that observed of a 3-dose schedule of Gardasil 9 among women aged 16-26 years old. The investigators thought that having a 2-dose vaccination regimen for individuals 16 to 45 would provide a more robust dataset than those of 27 to 45 years old.

Detailed Description
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The investigators will identify potential eligible subjects from the Boston Medical Center (BMC) Clinical Data Warehouse from the following BMC clinics: Pediatrics, Adolescent Medicine, Family Medicine, Obstetric/ Gynecology (OB/GYN), and Women's Health/Adult Primary Care. The research team will mail a recruitment opt-out letter signed by the principal investigator to the participant along with a study flyer. The recruitment letter will inform the participant that a research member may contact them via phone within two week to provide more information regarding the study. Participants opting-in will be called and interviewed with the study recruitment script and eligibility will be determined. Eligible participants who agree to participate (in-person or over the phone), will be scheduled to come to the Boston University (BU) General Clinical Research Unit (GCRU) to complete the consent process. At the baseline visit participants will be assigned into the appropriate group (control vs. intervention) based on their age.

Official Title
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An Open-Label Clinical Trial Evaluating the Immunogenicity of the 9vHPV Vaccination Regimen Over 6 Months Among Women Aged 16 to 45 Years Old, An Exploratory Immunogenicity Study

Conditions
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HPV Infection

Intervention / Treatment
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* Drug: Gardasil 9 2 dose regimen
* Drug: Gardasil 9 3 dose regimen
* Drug: Gardasil 9 rescue dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women receiving care at Boston Medical Center Exclusion Criteria: Currently pregnant Prior HPV vaccination A history of severe allergic reaction, including known allergy to any vaccine component, specially severe allergic to yeast Immunocompromised/previous immunosuppressive therapy Thrombocytopenia or other coagulation disorder Currently breastfeeding

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The control group will have 120 subjects will receive a 3-dose regimen as recommended by Center for Disease Control (CDC) given at 0, 2 and 6 months. The intervention group will have 240 subjects who will receive a modified 3-dose regimen given at 0, 6, and 12 months. Both groups will have HPV titers drawn at Visit 1 (pre-vaccination) and Visit 7 (after three doses for the Control group and 2 doses for the Intervention group).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>240 eligible women will receive a 2-dose regimen of Gardasil 9 at (0 and 6 months, followed by a rescue 3rd dose at month 12) | Drug: Gardasil 9 2 dose regimen<br>* a 2-dose regimen of Gardasil 9 at 0 and 6 months<br>* Other names: Human Papillomavirus 9-valent Vaccine, Recombinant;Drug: Gardasil 9 rescue dose<br>* A rescue dose of Gardasil 9 will be given at 12 months<br>* Other names: Human Papillomavirus 9-valent Vaccine, Recombinant;|
| Active Comparator: Control group<br>120 eligible women will receive the standard 3-dose regimen of Gardasil 9 at (0, 2, 6 months) | Drug: Gardasil 9 3 dose regimen<br>* standard 3-dose regimen of Gardasil 9 at 0, 2, 6 months<br>* Other names: Human Papillomavirus 9-valent Vaccine, Recombinant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in immunogenicity of Gardasil 9 | Immunogenicity will be measured by serum antibodies assessed by ELISA to the nine HPV types (anti-HPV 6/11/16/18/31/33/45/ 52/58 where positive anti-HPV serum levels are defined as >30, >16, >20, >24, >10, >8, >8, >8, or >8 milli Merck units (mMU)/mL respectively). | baseline and 7 months | 
| Change in geometric mean titers ratios | The geometric mean titers (GMT) ratios will be determined by a post-vaccination geometric mean titer (GMT) ratio with a pre-stated analysis of variance model (95% Confidence Interval lower bound >0.5). | baseline and 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with HPV seropositivity at day 1 | The number of participant who test positive in mili Unit (nMU) which will be will be defined as anti-HPV 6/11/16/18/31/33/45/ 52/58 positive if her anti-HPV serum level is >30, >16, >20, >24, >10, >8, >8, >8, or >8 milli Merck units (mMU)/mL for the 9 types, respectively. The serum testing will be under the direction of Merck research lab. | day 1 | 
| Number of participants with HPV seropositivity at month 7 | The number of participant who test positive in mili Unit (nMU) which will be will be defined as anti-HPV 6/11/16/18/31/33/45/ 52/58 positive if her anti-HPV serum level is >30, >16, >20, >24, >10, >8, >8, >8, or >8 milli Merck units (mMU)/mL for the 9 types, respectively. The serum testing will be under the direction of Merck research lab. | month 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gardasil, Immunogenicity, 9-valent 2-dose HPV vaccination, 9-valent 3-dose HPV vaccination