Gardasil Immunogenicity With Needle-Free Injection

Study Overview
=================
Brief Summary
-----------------
Using biospecimens collected in a trial by the Thai Red Cross AIDS Research Center that studied two new human papillomavirus (HPV) vaccine delivery regimens, the investigators at UCSF will be testing the serum for antibodies to measure the strength of their response to the vaccine.

Detailed Description
-----------------
Primary Objectives Compared rates of seroconversion and geometric mean titers (GMTs) generated following a 3-dose series of vaccine in women given low doses of vaccine by the intradermal (ID) route with the needle-free injector (NFI) (Group III) to those women given standard doses by the intramuscular (IM) route with a needle and syringe (Group I) at 1 month, 6 months and 12 months following completion of the vaccination series. Compared rates of seroconversion and GMTs generated following a 3-dose series of vaccine in women given standard doses of vaccine by the IM route with the NFI (Group II) to those women given standard doses by the IM route with a needle and syringe (Group I) at 1 month, 6 months and 12 months following completion of the vaccination series. Serum samples were collected on 4 successive occasions: (1) day zero, prior to the first immunization, (2) at visit 4, one month following the third and final immunization, (3) at visit 5 (12 months) and (4) and at visit 6 (24 months after enrollment). Samples were split, stored and transferred in batch for analysis. Merck received samples for processing and determined the geometric mean titer of antibodies specific to HPV (types 6, 11, 16, and 18) and results were transferred to the principal investigator. The University of California, San Francisco (UCSF) used a portion of the collected blood samples for pseudovirion-based neutralisation assay (PBNA) analysis conducted at UCSF.

Official Title
-----------------
GINI: Gardasil Immunogenicity With Needle-free Injection-Safety and Immunogenicity of Gardasil Using IM and ID Needle-free Injection Delivery

Conditions
-----------------
HPV Seroconversion

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Thai women age 18-26 years No more than 5 lifetime sexual partners HIV-uninfected No history of HPV vaccination Judged able to complete all of the protocol visits No contraindications to vaccination with Gardasil Exclusion Criteria: - Does not satisfy all of the inclusion criteria

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 26 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Standard intramuscular injection (NS-IM)<br>HPV vaccination regimen: Standard 3 dose (0.5mL) delivered by standard intramuscular (IM) injection using a needle and syringe (NS-IM) | |
| PharmaJet needle-free Stratis device (JI-IM)<br>HPV vaccination regimen: Standard 3 dose (0.5mL) delivered by IM injection using the PharmaJet needle-free Stratis device (JI-IM) | |
| PharmaJet needle-free Tropis device (JI-ID)<br>HPV vaccination regimen: Reduced-dose (0.1 mL) delivered by intradermal injection using the PharmaJet needle-free Tropis device (JI-ID) | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Geometric Mean Antibody Concentrations by HPV Type | Geometric mean antibody concentrations above the lower limit of assay detection at baseline were assessed by HPV type | Baseline, up to 1 day | 
| Percentage of Participants With a Demonstrated Seroconversion for HPV 6 | The percentage of participants with demonstrated seroconversion generated following a 3-dose series of vaccine for antibodies to HPV 6 at month 7 for the per-protocol efficacy population. The per-protocol efficacy population is defined as as those with month 7 result available, geometric mean antibody concentration below the cutoff level for positivity and undetectable baseline cervical HPV DNA. | Up to 7 months | 
| Percentage of Participants With a Demonstrated Seroconversion for HPV 11 | The percentage of participants with demonstrated seroconversion generated following a 3-dose series of vaccine for antibodies to HPV 11 at month 7 for the per-protocol efficacy population. The per-protocol efficacy population is defined as as those with month 7 result available, geometric mean antibody concentration below the cutoff level for positivity and undetectable baseline cervical HPV DNA. | Up to 7 months | 
| Percentage of Participants With a Demonstrated Seroconversion for HPV 16 | The percentage of participants with demonstrated seroconversion generated following a 3-dose series of vaccine for antibodies to HPV 16 at month 7 for the per-protocol efficacy population. The per-protocol efficacy population is defined as as those with month 7 result available, geometric mean antibody concentration below the cutoff level for positivity and undetectable baseline cervical HPV DNA. | Up to 7 months | 
| Percentage of Participants With a Demonstrated Seroconversion for HPV 18 | The percentage of participants with demonstrated seroconversion generated following a 3-dose series of vaccine for antibodies to HPV 18 at month 7 for the per-protocol efficacy population. The per-protocol efficacy population is defined as as those with month 7 result available, geometric mean antibody concentration below the cutoff level for positivity and undetectable baseline cervical HPV DNA. | Up to 7 months | 
| Median Concentration for HPV 6 Over Time | The median (mMU/mL) for HPV 6 at month 7 for the intent to treat population was calculated | Up to 7 months | 
| Median Concentration for HPV 11 Over Time | The median concentration (mMU/mL) for HPV 11 at month 7 for the intent to treat population was calculated | Up to 7 months | 
| Median Concentration for HPV 16 Over Time | The median concentration (mMU/mL) for HPV 16 at month 7 for the intent to treat population was calculated | Up to 7 months | 
| Median Concentration for HPV 18 Over Time | The median concentration (mMU/mL) for HPV 18 at month 7 for the intent to treat population was calculated | Up to 7 months | 
| Geometric Mean Concentration Ratio of NS-IM Versus the PharmaJet Groups by HPV Type | The Geometric Mean Concentration Ratio (GMCR) and 95% confidence interval for both NS-IM versus JI-IM and NS-IM versus JI-ID was computed for the intent to treat population. Non-inferiority for arms JI-IM and JI-ID was defined as geometric mean concentration ratio (GMCR) <1.5 of NS-IM at month 7 | Up to 7 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HPV, Gardasil, seroconversion