Broad Spectrum HPV Vaccine Dose Escalation Study (V502-002)

Study Overview
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Brief Summary
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This study will examine the safety and tolerability of octavalent Human Papillomavirus (HPV) L1 Virus-Like Particle (VLP) vaccine formulated with amorphous aluminum hydroxysulfate (AAHS) and ISCOMATRIX™ (IMX). Reviews of safety and tolerability will be used to select the dose(s) of IMX for further studies of the octavalent HPV L1 VLP vaccine.

Detailed Description
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The study was performed in 2 staggered phases, Phase A and Phase B. In Phase A, participants were randomized to qHPV, Octavalent HPV with 15 mcg IMX/AAHS, or Octavalent HPV with 30 mcg IMX/AAHS. After the safety for Phase A was reviewed, Phase B was initiated. In Phase B, participants were randomized to qHPV, Octavalent HPV with 60 mcg IMX/AAHS or Octavalent HPV with 120 mcg IMX/AAHS.

Official Title
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A Randomized, Double-Blind, Multicenter, Biphasic, Controlled With GARDASIL™ Dose-Escalation Study of Octavalent Human Papillomavirus (HPV) L1 Virus-Like Particle (VLP) Vaccine Adjuvanted With Amorphous Aluminum Hydroxyphosphate Sulfate (AAHS) and ISCOMATRIX™ (IMX)

Conditions
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Human Papilloma Virus, Cervical Cancer, Vulvar Cancer, Vaginal Cancer, Genital Warts

Intervention / Treatment
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* Biological: Octavalent HPV with 15 mcg IMX / AAHS
* Biological: Octavalent HPV with 30 mcg IMX / AAHS
* Biological: Octavalent HPV with 60 mcg IMX / AAHS
* Biological: Octavalent HPV with 120 mcg IMX / AAHS
* Biological: Comparator: Quadrivalent HPV Vaccine (qHPV), (GARDASIL™)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is in good physical health Participant has had a lifetime history of 0 to 4 sexual partners Females between 18-to-24 years Exclusion Criteria: Participant has a history of abnormal Pap test Participant has a history of positive test for HPV Participant has a history of recent or ongoing alcohol or drug abuse Participant is immunocompromised or has an autoimmune condition Participant has received immunosuppressive therapy within a year of screening Participant has previously received an HPV vaccine Participant is pregnant Participant has a history of external genital/vaginal warts Participant is currently enrolled in a clinical trial Participant has a history of a severe allergic reaction that required medical attention

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: qHPV (GARDASIL™) - Phase A Control<br>Quadrivalent Human Papillomavirus (qHPV) (Types 6, 11, 16, 18) Recombinant Vaccine (GARDASIL™). This is the control for the Octavalent HPV with 15 mcg ISCOMATRIX™ (IMX) / Aluminum Hydroxyphosphate Sulfate (AAHS) and Octavalent HPV with 30 mcg IMX / AAHS during Phase A. | Biological: Comparator: Quadrivalent HPV Vaccine (qHPV), (GARDASIL™)<br>* 0.5-mL intramuscular injection administered at Day 1, Month 2 and Month 6<br>* Other names: V502-002;|
| Experimental: Octavalent HPV with 15 mcg IMX / AAHS<br>Octavalent Human Papillomavirus (HPV) (Types 6, 11, 16, 18, 31, 45, 52, and 58) L1 Virus-Like Particle (VLP) Vaccine Adjuvanted With 281 mcg AAHS and 15 mcg IMX. | Biological: Octavalent HPV with 15 mcg IMX / AAHS<br>* 0.5-mL intramuscular injection administered at Day 1, Month 2 and Month 6<br>* Other names: V502;|
| Experimental: Octavalent HPV with 30 mcg IMX / AAHS<br>Octavalent Human Papillomavirus (HPV) (Types 6, 11, 16, 18, 31, 45, 52, and 58) L1 VLP Vaccine Adjuvanted With 281 mcg AAHS and 30 mcg IMX. | Biological: Octavalent HPV with 30 mcg IMX / AAHS<br>* 0.5-mL intramuscular injection administered at Day 1, Month 2 and Month 6<br>* Other names: V502;|
| Active Comparator: qHPV (GARDASIL™) - Phase B Control<br>Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine (GARDASIL™). This is the control for the Octavalent HPV with 60 mcg IMX / AAHS and Octavalent HPV with 120 mcg IMX / AAHS during Phase B. | Biological: Comparator: Quadrivalent HPV Vaccine (qHPV), (GARDASIL™)<br>* 0.5-mL intramuscular injection administered at Day 1, Month 2 and Month 6<br>* Other names: V502-002;|
| Experimental: Octavalent HPV with 60 mcg IMX / AAHS<br>Octavalent Human Papillomavirus (HPV) (Types 6, 11, 16, 18, 31, 45, 52, and 58) L1 VLP Vaccine Adjuvanted With 281 mcg AAHS and 60 mcg IMX. | Biological: Octavalent HPV with 60 mcg IMX / AAHS<br>* 0.5-mL intramuscular injection administered at Day 1, Month 2 and Month 6<br>* Other names: V502;|
| Experimental: Octavalent HPV with 120 mcg IMX / AAHS<br>Octavalent Human Papillomavirus (HPV) (Types 6, 11, 16, 18, 31, 45, 52, and 58) L1 VLP Vaccine Adjuvanted With 281 mcg AAHS and 120 mcg IMX. | Biological: Octavalent HPV with 120 mcg IMX / AAHS<br>* 0.5-mL intramuscular injection administered at Day 1, Month 2 and Month 6<br>* Other names: V502;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) to Each of the HPV Types Contained in the Vaccine for Phase A | The quadrivalent HPV (GARDASIL™) vaccine has types 6, 11, 16, 18, and the octavalent HPV has types 6, 11, 16, 18, 31, 45, 52, and 58. Serum antibody titres to the HPV type were obtained using a competitive Luminex immunoassay (cLIA) after vaccination with GARDASIL™ or the octavalent HPV vaccine. GMTs were calculated and are reported as the antibody concentration in milli-Merck Units per milliliter (mMU/mL) of neutralizing monoclonal antibody equivalent. | 4 weeks postdose 3 (Phase A) | 
| Geometric Mean Titers (GMTs) to Each of the HPV Types Contained in the Vaccine for Phase B | The quadrivalent HPV (GARDASIL™) vaccine has types 6, 11, 16, 18, and the octavalent HPV has types 6, 11, 16, 18, 31, 45, 52, and 58. Serum antibody titres to the HPV type were obtained using cLIA after vaccination with GARDASIL™ or the octavalent HPV vaccine. GMTs were calculated and are reported as the antibody concentration in milli-Merck Units per milliliter (mMU/mL) of neutralizing monoclonal antibody equivalent. | 4 weeks postdose 3 (Phase B) | 
| Number of Participants Who Seroconverted to Each of the HPV Types Contained in the Vaccine During Phase A | A vaccinated participant was considered seropositive for a given HPV type if her serum antibody titer by cLIA for the HPV type was greater than the serostatus cutoff. The serostatus cutoffs for HPV Types 6, 11, 16, 18, 31, 45, 52, and 58 were 20, 20, 20, 20, 16, 16, 20, and 16 mMU/mL, respectively. | 4 weeks postdose 3 (Phase A) | 
| Number of Participants Who Seroconverted to Each of the HPV Types Contained in the Vaccine During Phase B | A vaccinated participant was considered seropositive for a given HPV type if her serum antibody titer by cLIA for the HPV type was greater than the serostatus cutoff. The serostatus cutoffs for HPV Types 6, 11, 16, 18, 31, 45, 52, and 58 were 20, 20, 20, 20, 16, 16, 20, and 16 mMU/mL, respectively. | 4 weeks postdose 3 (Phase B) |