Preparedness Study - HPV Vaccine

Study Overview
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Brief Summary
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Moffitt Cancer Center is the Coordinating Center for this study. The purpose of this study is to develop and test the infrastructure to conduct a future Phase III vaccine efficacy trial to assess trial feasibility, and to assess human papillomavirus (HPV) genotype distribution, data needed to design a Phase III trial. The investigators propose to conduct a Preparedness study among women ages 16-24 years of age residing in a region of South Africa with a high human immunodeficiency (HIV) incidence and prevalence. The specific aims of this study are to: Identify, recruit, enroll, and randomize a cohort of HIV negative women (200 per arm, 400 total) ages 16-24 years to an HPV vaccine against 4 types (HPV 6, 11, 16, 18 [Gardasil]) or placebo vaccine. Determine the cervical HPV prevalence and type distribution at enrollment, and cervical lesion prevalence among young females ages 16-24 years at high risk for HIV infection. Assess the rate of compliance through the 3-dose vaccination series

Detailed Description
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The study vaccine will be blindly administered as supplied on Day 1, Month 2, and Month 6. Both HPV and placebo vaccines will be in identical bottles, and all treatment codes will be kept under lock and key. All vaccines will be injected intramuscularly into the deltoid muscle by a member of the clinical staff. Each participant will be monitored for systemic and local reactions for 30 minutes postvaccination after each study vaccination for any adverse effects, including allergic reactions. Vaccine adverse events will continue to be monitored throughout the duration of the study period. Vaccine will be shipped to a central pharmacy at Stellenbosch University and stored in a refrigerator monitored and maintained at 2-8 C prior to distribution and local storage at participating clinical centers.

Official Title
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Preparedness Study: Efficacy of HPV Vaccine to Reduce HIV Infection

Conditions
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Sexual Transmission of Infection

Intervention / Treatment
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* Biological: Gardasil Vaccine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women ages 16-24 years of age residing in a region of South Africa with a high HIV incidence and prevalence HIV negative has ever had vaginal intercourse has never had Papanicolaou smear (Pap) testing or has only had normal Pap test results fully understands study procedures, risks involved in the study, and voluntarily agrees to participate by giving written informed consent agrees to refrain from douching/vaginal cleansing and using vaginal medications or preparations for 2 calendar days prior to the Day 1 visit as well as other future visits that include collection of cervical specimens agrees to refrain from sexual intercourse for 2 calendar days prior to the Day 1 visit as well as other future visits that include collection of cervical specimens agrees to utilize effective contraception during sexual intercourse (excluding the rhythm method, withdrawal alone, and emergency contraception) during the vaccination period. Informed consent procedures for females <18 years of age: Informed consent and informed assent will be obtained from parents/legal guardians and adolescents respectively, prior to participation. The consent form will include information about the study and individual request for consent of participants to participate in the study. It will be emphasized that participation is voluntary and that participants are free to withdraw from the study at any stage without any disadvantage to them. An assessment of understanding will be conducted at screening to ensure that consent is informed. Exclusion Criteria: have a history of severe allergic reaction have a known allergy to any vaccine component (e.g., aluminum, yeast, or BENZONASE) are currently immuno-compromised have received a marketed HPV vaccine, or are pregnant and lactating

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 24 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gardasil Vaccine Administration<br>Gardasil Vaccine Administration. Family Health International (FHI) statisticians randomly assigned each participant an allocation number and then subsequently assigned a unique vial identification number for the vial of vaccine the participant should receive at each visit. A single participant could not be assigned more than 1 allocation number. | Biological: Gardasil Vaccine<br>* The study vaccine was blindly administered as supplied on Day 1, Month 2, and Month 6. All vaccines were injected intramuscularly into the deltoid muscle by a member of the clinical staff.<br>* Other names: Gardasil;|
| Placebo Comparator: Placebo Administration<br>Placebo Administration. Family Health International (FHI) statisticians randomly assigned each participant an allocation number and then subsequently assigned a unique vial identification number for the vial of vaccine the participant should receive at each visit. A single participant could not be assigned more than 1 allocation number. | Other: Placebo<br>* The study vaccine was blindly administered as supplied on Day 1, Month 2, and Month 6. All vaccines were injected intramuscularly into the deltoid muscle by a member of the clinical staff.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Human Papillomavirus (HPV) Rate | HPV type distribution and prevalence of each HPV type at enrollment. | At Enrollment - 5 Month Enrollment Period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study Compliance Rate | Percentage of participants to complete the 3-dose vaccination series and all 4 study visits. | 18 Months | 
| Percentage of Participants Who Were Seropositive by HPV Type | Percentage of participants who were seropositive to HPV at enrollment, by specific HPV type. | At Enrollment - 5 Month Enrollment Period | 
| Percentage of Participants Seroconverted to HPV Types 6, 11, 16, or 18 | Percentage of participants who seroconverted to HPV types 6, 11, 16, or 18, following receipt of 3 doses of qHPV vaccine. | 18 Months | 
| Percentage of Participants Who Seroconverted to HPV Types 31, 33, 45, or 58 | The percent of women that seroconverted among those receiving qHPV vaccine compared to placebo vaccine recipients for HPV types 31, 33, 45, and 58, HPV types not directly targeted by the qHPV vaccine. | 18 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, Placebo, sexually transmitted infection (STI), HIV, Human Immunodeficiency, Gardasil, HPV, human papillomavirus