A Controlled Trial to Assess the Immunogenicity of a Proposed Paediatric Dosing Schedule of Human Papillomavirus Vaccine

Study Overview
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Brief Summary
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Primary objective is to determine if antibody responses to HPV types 16 & 18 are non-inferior after a 2-dose paediatric regimen as compared to a 3-dose adult regimen of Q-HPV vaccination, with responses measured at Month 7.

Detailed Description
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Human Papillomavirus (HPV) infection is a cause of cervical cancer. Immunogenicity, safety and efficacy in the prevention of persistent infection from HPV 16 and 18 has been proven using a 3-dose regimen in adolescent and adult females using the Quadrivalent Human Papillomavirus (Q-HPV) vaccine. The intensity of the immune response is inversely proportional to age. Immunogenicity in adolescents 9-15 years of age is 1.7 - 2 times greater than in 16-26 year old vaccine recipients. Paediatric dosing studies are necessary and prudent given limited provincial funding for new biologics acquisition and programme service delivery. A reduction from an adult 3-dose HPV vaccine regimen to a pediatric 2-dose regimen will result in increased compliance to the full vaccine series and in significant savings to the health care system both in the cost of biologics and of program delivery and administration.

Official Title
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A Controlled Trial to Assess the Immunogenicity of a Proposed Paediatric Dosing Schedule of Human Papillomavirus Vaccine

Conditions
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Cervical Cancer, Genital Warts

Intervention / Treatment
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* Biological: HPV (Human Papillomavirus) Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A female between, and including, 9-13 years (before 14th birthday) and 16-26 years of age (before 27th birthday) at the time of the first vaccination. Healthy Not pregnant Four or less sexual partners over lifetime as reported by subject. (Sexual activity is defined as intercourse) Not planning to become pregnant or likely to become pregnant No reported history of genital warts No laboratory confirmed history of cervical intraepithelial neoplasia No previous vaccination against HPV No administration of immunoglobulin and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period No previous anaphylactic reaction to HPV vaccine or any vaccine related component including aluminum hydroxyphosphate sulfate and polysorbate 80 No confirmed or suspected immunosuppressive or immunodeficient condition based on medical history No bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection. Cannot be already enrolled in any clinical trial in which investigational vaccine or drug are being administered Exclusion Criteria Pregnant Female planning to become pregnant or likely to become pregnant (as determined by the investigator) during the study duration Part 1 (0-7 months) Reported history of genital warts Laboratory confirmed history of cervical intraepithelial neoplasia Greater than four lifetime sexual partners involving sexual intercourse Previous vaccination against HPV Administration of immunoglobulin and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period A previous anaphylactic reaction to HPV vaccine or any vaccine related component including aluminum hydroxyphosphate sulfate and polysorbate 80 Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history (e.g. HIV infection, genetic defect, immunosuppressive therapy). *Chronic administration (defined as more than 14 days) of immune-modifying drugs within 6 months prior to the first vaccine dose or planned use during the study period is exclusionary (corticosteroid use - immune-modifying level is ≥0.5 mg/kg/day; inhaled or topical steroids are acceptable). Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection (thrombocytopaenia, coagulation disorder, anti-coagulant therapy). Enrollment in any clinical trial in which investigational vaccine or drug are being administered

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 26 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 16-26 year olds 3 doses HPV Vaccine<br>Group 3 - 16-26 year olds receiving 3 doses HPV (Human Papillomavirus) Vaccine at 0, 2, 6 mths | Biological: HPV (Human Papillomavirus) Vaccine<br>* HPV (Human Papillomavirus) Vaccine received by all participants in groups 1, 2 and 3 according to the arm<br>* Other names: HPV Vaccine;|
| Active Comparator: 3 dose 9-13 HPV Vaccine<br>Group 2 - 9-13 year olds receiving 3 doses HPV (Human Papillomavirus) Vaccine at 0,2,6 mths | Biological: HPV (Human Papillomavirus) Vaccine<br>* HPV (Human Papillomavirus) Vaccine received by all participants in groups 1, 2 and 3 according to the arm<br>* Other names: HPV Vaccine;|
| Active Comparator: 2 dose 9-13 yrs HPV Vaccine<br>Group 1 9-13 year olds 2 doses HPV (Human Papillomavirus) Vaccine at 0 and 6 mths | Biological: HPV (Human Papillomavirus) Vaccine<br>* HPV (Human Papillomavirus) Vaccine received by all participants in groups 1, 2 and 3 according to the arm<br>* Other names: HPV Vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Objective Part 1 | To determine if antibody responses to HPV types 16 & 18 are non-inferior after a 2-dose paediatric regimen as compared to a 3-dose adult regimen of Q-HPV vaccination | Measured after Month 7 | 
| Primary Objective Part 2 | To compare the serum antibody responses to HPV 6, 11, 16 & 18 at months 18, 24 and 36 in 2-dose adolescent arm, 3-dose adolescent arm and 3-dose adult arm of the study. | At 18, 24 and 36mths post dose 1 | 
| Primary Objective Part 2 | To evaluate the memory B cell and T helper cell mediated immune response to Q-HPV vaccine in the 2-dose adolescent, 3-dose adolescent and 3-dose adult arms | Measured at 36 mths | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Objective Part 1 & 2 - Antibody responses 2 doses between 9-13 vs 16-26 | To demonstrate that 2-doses of Q-HPV vaccine administered to 9-13 year old females produces a serum antibody response to HPV 6 and 11 that is similar to the response seen in 16-26 year olds | Measured at 7, 18,24 and 36 mths | 
| Secondary Objective Part 1 & 2 - HPV 16 and 18 2 doses versus 3 | To evaluate the antibody responses to HPV 16 and 18 in 9-13 year old females after a 2-dose versus a 3-dose Q-HPV regimen | Measured at 7,18,24 and 36 mths | 
| Secondary Objective Part 1 seroconversion rates | To evaluate seroconversion rates to HPV 6, 11, 16, and 18 | Measured at 7 mths | 
| Secondary Objective Part 1 Memory Response | To evaluate the memory B cell and T helper cell mediated immune response to Q-HPV vaccine in the 2-dose adolescent, 3-dose adolescent and 3-dose adult arms | Measured at 7 mths | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV, HPV vaccine, Gardasil, Human Papillomavirus, vaccine, 2 dose versus 3