HPV Seroconversion
Conditions
Keywords
HPV, Gardasil, seroconversion
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 1. 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. 2. 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.
Interventions
None listed
Sponsors
Merck Sharp & Dohme LLC
University of California, San Francisco
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 26 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Concentration for HPV 16 Over Time | Up to 7 months | The median concentration (mMU/mL) for HPV 16 at month 7 for the intent to treat population was calculated |
| Median Concentration for HPV 18 Over Time | Up to 7 months | The median concentration (mMU/mL) for HPV 18 at month 7 for the intent to treat population was calculated |
| Median Concentration for HPV 11 Over Time | Up to 7 months | The median concentration (mMU/mL) for HPV 11 at month 7 for the intent to treat population was calculated |
| Number of Participants With Geometric Mean Antibody Concentrations by HPV Type | Baseline, up to 1 day | Geometric mean antibody concentrations above the lower limit of assay detection at baseline were assessed by HPV type |
| Percentage of Participants With a Demonstrated Seroconversion for HPV 6 | Up to 7 months | 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. |
| Percentage of Participants With a Demonstrated Seroconversion for HPV 11 | Up to 7 months | 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. |
| Percentage of Participants With a Demonstrated Seroconversion for HPV 16 | Up to 7 months | 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. |
| Percentage of Participants With a Demonstrated Seroconversion for HPV 18 | Up to 7 months | 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. |
| Median Concentration for HPV 6 Over Time | Up to 7 months | The median (mMU/mL) for HPV 6 at month 7 for the intent to treat population was calculated |
| Geometric Mean Concentration Ratio of NS-IM Versus the PharmaJet Groups by HPV Type | Up to 7 months | 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 |
Countries
Thailand, United States
Participant flow
Recruitment details
161 women visiting the Thai Red Cross Anonymous Clinic between February 2014 and April 2014 were invited to participate in the study and were screened after providing informed consent. Eleven women were determined to be ineligible
Participants by arm
| Arm | Count |
|---|---|
| Standard Intramuscular Injection (NS-IM) HPV vaccination regimen: Standard 3 dose (0.5mL) delivered by standard intramuscular (IM) injection using a needle and syringe | 50 |
| PharmaJet Needle-free Stratis Device (JI-IM) HPV vaccination regimen: Standard 3 dose (0.5mL) delivered by IM injection using the PharmaJet needle-free Stratis device | 50 |
| PharmaJet Needle-free Tropis Device (JI-ID) HPV vaccination regimen: Reduced-dose (0.1 mL) delivered by intradermal injection using the PharmaJet needle-free Tropis device | 50 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 | 1 |
| Overall Study | Pregnancy | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | PharmaJet Needle-free Stratis Device (JI-IM) | Total | Standard Intramuscular Injection (NS-IM) | PharmaJet Needle-free Tropis Device (JI-ID) |
|---|---|---|---|---|
| Age, Continuous | 23.4 years | 23.7 years | 23.3 years | 24.5 years |
| Number of HPV genotypes detected at Baseline 1 type | 4 Participants | 27 Participants | 18 Participants | 5 Participants |
| Number of HPV genotypes detected at Baseline 2 types | 1 Participants | 3 Participants | 0 Participants | 2 Participants |
| Number of HPV genotypes detected at Baseline >= 3 types | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Positive cervical HPV DNA at Baseline HPV-11 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Positive cervical HPV DNA at Baseline HPV-16 | 5 Participants | 18 Participants | 12 Participants | 1 Participants |
| Positive cervical HPV DNA at Baseline HPV-18 | 1 Participants | 7 Participants | 3 Participants | 3 Participants |
| Positive cervical HPV DNA at Baseline HPV-6 | 2 Participants | 8 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 50 Participants | 150 Participants | 50 Participants | 50 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Thailand | 50 participants | 50 participants | 50 participants | 50 participants |
| Sex: Female, Male Female | 50 Participants | 150 Participants | 50 Participants | 50 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 | 0 / 50 |
| other Total, other adverse events | 45 / 50 | 46 / 50 | 36 / 50 |
| serious Total, serious adverse events | 2 / 50 | 3 / 50 | 2 / 50 |
Outcome results
Primary
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
Time frame: Up to 7 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard Intramuscular Injection (NS-IM) | Geometric Mean Concentration Ratio of NS-IM Versus the PharmaJet Groups by HPV Type | HPV-6 | 1.37 ratio |
| Standard Intramuscular Injection (NS-IM) | Geometric Mean Concentration Ratio of NS-IM Versus the PharmaJet Groups by HPV Type | HPV-11 | 1.36 ratio |
| Standard Intramuscular Injection (NS-IM) | Geometric Mean Concentration Ratio of NS-IM Versus the PharmaJet Groups by HPV Type | HPV-16 | 1.47 ratio |
| Standard Intramuscular Injection (NS-IM) | Geometric Mean Concentration Ratio of NS-IM Versus the PharmaJet Groups by HPV Type | HPV-18 | 1.23 ratio |
| PharmaJet Needle-free Stratis Device (JI-IM) | Geometric Mean Concentration Ratio of NS-IM Versus the PharmaJet Groups by HPV Type | HPV-18 | 1.52 ratio |
| PharmaJet Needle-free Stratis Device (JI-IM) | Geometric Mean Concentration Ratio of NS-IM Versus the PharmaJet Groups by HPV Type | HPV-6 | 1.84 ratio |
| PharmaJet Needle-free Stratis Device (JI-IM) | Geometric Mean Concentration Ratio of NS-IM Versus the PharmaJet Groups by HPV Type | HPV-16 | 1.97 ratio |
| PharmaJet Needle-free Stratis Device (JI-IM) | Geometric Mean Concentration Ratio of NS-IM Versus the PharmaJet Groups by HPV Type | HPV-11 | 1.61 ratio |
Primary
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
Time frame: Up to 7 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard Intramuscular Injection (NS-IM) | Median Concentration for HPV 11 Over Time | Baseline | 8 mMU/mL |
| Standard Intramuscular Injection (NS-IM) | Median Concentration for HPV 11 Over Time | Month 7 | 517.5 mMU/mL |
| PharmaJet Needle-free Stratis Device (JI-IM) | Median Concentration for HPV 11 Over Time | Baseline | 8 mMU/mL |
| PharmaJet Needle-free Stratis Device (JI-IM) | Median Concentration for HPV 11 Over Time | Month 7 | 484 mMU/mL |
| PharmaJet Needle-free Tropis Device (JI-ID) | Median Concentration for HPV 11 Over Time | Baseline | 8 mMU/mL |
| PharmaJet Needle-free Tropis Device (JI-ID) | Median Concentration for HPV 11 Over Time | Month 7 | 387 mMU/mL |
Primary
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
Time frame: Up to 7 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard Intramuscular Injection (NS-IM) | Median Concentration for HPV 16 Over Time | Baseline | 11 mMU/mL |
| Standard Intramuscular Injection (NS-IM) | Median Concentration for HPV 16 Over Time | Month 7 | 2243.5 mMU/mL |
| PharmaJet Needle-free Stratis Device (JI-IM) | Median Concentration for HPV 16 Over Time | Baseline | 11 mMU/mL |
| PharmaJet Needle-free Stratis Device (JI-IM) | Median Concentration for HPV 16 Over Time | Month 7 | 2054.5 mMU/mL |
| PharmaJet Needle-free Tropis Device (JI-ID) | Median Concentration for HPV 16 Over Time | Baseline | 11 mMU/mL |
| PharmaJet Needle-free Tropis Device (JI-ID) | Median Concentration for HPV 16 Over Time | Month 7 | 1482 mMU/mL |
Primary
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
Time frame: Up to 7 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard Intramuscular Injection (NS-IM) | Median Concentration for HPV 18 Over Time | Baseline | 10 mMU/mL |
| Standard Intramuscular Injection (NS-IM) | Median Concentration for HPV 18 Over Time | Month 7 | 412.5 mMU/mL |
| PharmaJet Needle-free Stratis Device (JI-IM) | Median Concentration for HPV 18 Over Time | Baseline | 10 mMU/mL |
| PharmaJet Needle-free Stratis Device (JI-IM) | Median Concentration for HPV 18 Over Time | Month 7 | 414.5 mMU/mL |
| PharmaJet Needle-free Tropis Device (JI-ID) | Median Concentration for HPV 18 Over Time | Baseline | 10 mMU/mL |
| PharmaJet Needle-free Tropis Device (JI-ID) | Median Concentration for HPV 18 Over Time | Month 7 | 372.5 mMU/mL |
Primary
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
Time frame: Up to 7 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard Intramuscular Injection (NS-IM) | Median Concentration for HPV 6 Over Time | Baseline | 11 mMU/mL |
| Standard Intramuscular Injection (NS-IM) | Median Concentration for HPV 6 Over Time | Month 7 | 449.5 mMU/mL |
| PharmaJet Needle-free Stratis Device (JI-IM) | Median Concentration for HPV 6 Over Time | Baseline | 11 mMU/mL |
| PharmaJet Needle-free Stratis Device (JI-IM) | Median Concentration for HPV 6 Over Time | Month 7 | 311 mMU/mL |
| PharmaJet Needle-free Tropis Device (JI-ID) | Median Concentration for HPV 6 Over Time | Baseline | 11 mMU/mL |
| PharmaJet Needle-free Tropis Device (JI-ID) | Median Concentration for HPV 6 Over Time | Month 7 | 259.5 mMU/mL |
Primary
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
Time frame: Baseline, up to 1 day
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard Intramuscular Injection (NS-IM) | Number of Participants With Geometric Mean Antibody Concentrations by HPV Type | HPV-6 | 15 Participants |
| Standard Intramuscular Injection (NS-IM) | Number of Participants With Geometric Mean Antibody Concentrations by HPV Type | HPV-11 | 4 Participants |
| Standard Intramuscular Injection (NS-IM) | Number of Participants With Geometric Mean Antibody Concentrations by HPV Type | HPV-16 | 14 Participants |
| Standard Intramuscular Injection (NS-IM) | Number of Participants With Geometric Mean Antibody Concentrations by HPV Type | HPV-18 | 6 Participants |
| PharmaJet Needle-free Stratis Device (JI-IM) | Number of Participants With Geometric Mean Antibody Concentrations by HPV Type | HPV-18 | 4 Participants |
| PharmaJet Needle-free Stratis Device (JI-IM) | Number of Participants With Geometric Mean Antibody Concentrations by HPV Type | HPV-6 | 12 Participants |
| PharmaJet Needle-free Stratis Device (JI-IM) | Number of Participants With Geometric Mean Antibody Concentrations by HPV Type | HPV-16 | 9 Participants |
| PharmaJet Needle-free Stratis Device (JI-IM) | Number of Participants With Geometric Mean Antibody Concentrations by HPV Type | HPV-11 | 2 Participants |
| PharmaJet Needle-free Tropis Device (JI-ID) | Number of Participants With Geometric Mean Antibody Concentrations by HPV Type | HPV-18 | 4 Participants |
| PharmaJet Needle-free Tropis Device (JI-ID) | Number of Participants With Geometric Mean Antibody Concentrations by HPV Type | HPV-11 | 6 Participants |
| PharmaJet Needle-free Tropis Device (JI-ID) | Number of Participants With Geometric Mean Antibody Concentrations by HPV Type | HPV-16 | 8 Participants |
| PharmaJet Needle-free Tropis Device (JI-ID) | Number of Participants With Geometric Mean Antibody Concentrations by HPV Type | HPV-6 | 8 Participants |
Primary
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.
Time frame: Up to 7 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Intramuscular Injection (NS-IM) | Percentage of Participants With a Demonstrated Seroconversion for HPV 11 | 100 percentage of participants |
| PharmaJet Needle-free Stratis Device (JI-IM) | Percentage of Participants With a Demonstrated Seroconversion for HPV 11 | 100 percentage of participants |
| PharmaJet Needle-free Tropis Device (JI-ID) | Percentage of Participants With a Demonstrated Seroconversion for HPV 11 | 100 percentage of participants |
Primary
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.
Time frame: Up to 7 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Intramuscular Injection (NS-IM) | Percentage of Participants With a Demonstrated Seroconversion for HPV 16 | 100 percentage of participants |
| PharmaJet Needle-free Stratis Device (JI-IM) | Percentage of Participants With a Demonstrated Seroconversion for HPV 16 | 97.4 percentage of participants |
| PharmaJet Needle-free Tropis Device (JI-ID) | Percentage of Participants With a Demonstrated Seroconversion for HPV 16 | 100 percentage of participants |
Primary
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.
Time frame: Up to 7 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Intramuscular Injection (NS-IM) | Percentage of Participants With a Demonstrated Seroconversion for HPV 18 | 100 percentage of participants |
| PharmaJet Needle-free Stratis Device (JI-IM) | Percentage of Participants With a Demonstrated Seroconversion for HPV 18 | 97.6 percentage of participants |
| PharmaJet Needle-free Tropis Device (JI-ID) | Percentage of Participants With a Demonstrated Seroconversion for HPV 18 | 97.6 percentage of participants |
Primary
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.
Time frame: Up to 7 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Intramuscular Injection (NS-IM) | Percentage of Participants With a Demonstrated Seroconversion for HPV 6 | 100 percentage of participants |
| PharmaJet Needle-free Stratis Device (JI-IM) | Percentage of Participants With a Demonstrated Seroconversion for HPV 6 | 97.2 percentage of participants |
| PharmaJet Needle-free Tropis Device (JI-ID) | Percentage of Participants With a Demonstrated Seroconversion for HPV 6 | 100 percentage of participants |