Sexual Transmission of Infection
Conditions
Keywords
Vaccine, Placebo, sexually transmitted infection (STI), HIV, Human Immunodeficiency, Gardasil, HPV, human papillomavirus
Brief summary
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: 1. 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. 2. 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. 3. Assess the rate of compliance through the 3-dose vaccination series
Detailed description
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.
Interventions
BIOLOGICALGardasil Vaccine
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.
OTHERPlacebo
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.
Sponsors
Merck Sharp & Dohme LLC
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 24 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Human Papillomavirus (HPV) Rate | At Enrollment - 5 Month Enrollment Period | HPV type distribution and prevalence of each HPV type at enrollment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Study Compliance Rate | 18 Months | Percentage of participants to complete the 3-dose vaccination series and all 4 study visits. |
| Percentage of Participants Who Were Seropositive by HPV Type | At Enrollment - 5 Month Enrollment Period | Percentage of participants who were seropositive to HPV at enrollment, by specific HPV type. |
| Percentage of Participants Seroconverted to HPV Types 6, 11, 16, or 18 | 18 Months | Percentage of participants who seroconverted to HPV types 6, 11, 16, or 18, following receipt of 3 doses of qHPV vaccine. |
| Percentage of Participants Who Seroconverted to HPV Types 31, 33, 45, or 58 | 18 Months | 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. |
Countries
South Africa, United States
Participant flow
Recruitment details
Women residing in the Western Cape, South Africa were enrolled from November 2012 to July 2013 in a preparedness study. Participants were recruited from the Kraaifontein day hospital and the Bloekombos primary health care clinic by community workers and through word of mouth, flyers, and brochures.
Pre-assignment details
4 of the 406 participants randomized had a false HIV negative test result, reducing the participants to 202 in the Gardasil Arm and 200 in the Placebo Arm.
Participants by arm
| Arm | Count |
|---|---|
| Gardasil Vaccine Administration Gardasil Vaccine injected intramuscularly into the deltoid or thigh muscle. | 202 |
| Placebo Administration Placebo injected intramuscularly into the deltoid or thigh muscle. | 200 |
| Total | 402 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 1 |
| Overall Study | Not compliant | 1 | 0 |
| Overall Study | Participant moved | 6 | 7 |
| Overall Study | Pregnancy | 9 | 14 |
| Overall Study | Procedures | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 4 |
Baseline characteristics
| Characteristic | Gardasil Vaccine Administration | Placebo Administration | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 40 Participants | 46 Participants | 86 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 162 Participants | 154 Participants | 316 Participants |
| Age, Continuous | 20 years | 20 years | 20 years |
| Region of Enrollment South Africa | 202 participants | 200 participants | 402 participants |
| Sex: Female, Male Female | 202 Participants | 200 Participants | 402 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 59 / 202 | 62 / 200 |
| serious Total, serious adverse events | 0 / 202 | 0 / 200 |
Outcome results
Primary
Human Papillomavirus (HPV) Rate
HPV type distribution and prevalence of each HPV type at enrollment.
Time frame: At Enrollment - 5 Month Enrollment Period
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gardasil Vaccine Administration | Human Papillomavirus (HPV) Rate | HPV18 | 11 participants |
| Gardasil Vaccine Administration | Human Papillomavirus (HPV) Rate | Any HPV Type | 143 participants |
| Gardasil Vaccine Administration | Human Papillomavirus (HPV) Rate | Any High-Risk Type | 106 participants |
| Gardasil Vaccine Administration | Human Papillomavirus (HPV) Rate | Any Low-Risk Type | 103 participants |
| Gardasil Vaccine Administration | Human Papillomavirus (HPV) Rate | HPV6 | 9 participants |
| Gardasil Vaccine Administration | Human Papillomavirus (HPV) Rate | HPV11 | 2 participants |
| Gardasil Vaccine Administration | Human Papillomavirus (HPV) Rate | HPV16 | 23 participants |
| Placebo Administration | Human Papillomavirus (HPV) Rate | HPV18 | 14 participants |
| Placebo Administration | Human Papillomavirus (HPV) Rate | HPV6 | 3 participants |
| Placebo Administration | Human Papillomavirus (HPV) Rate | Any HPV Type | 136 participants |
| Placebo Administration | Human Papillomavirus (HPV) Rate | HPV16 | 32 participants |
| Placebo Administration | Human Papillomavirus (HPV) Rate | Any High-Risk Type | 113 participants |
| Placebo Administration | Human Papillomavirus (HPV) Rate | HPV11 | 2 participants |
| Placebo Administration | Human Papillomavirus (HPV) Rate | Any Low-Risk Type | 97 participants |
Secondary
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.
Time frame: 18 Months
Population: Participants who were randomized to Gardasil and received all 3 doses of Gardasil
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil Vaccine Administration | Percentage of Participants Seroconverted to HPV Types 6, 11, 16, or 18 | 100 percentage of participants |
Secondary
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.
Time frame: 18 Months
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gardasil Vaccine Administration | Percentage of Participants Who Seroconverted to HPV Types 31, 33, 45, or 58 | HPV31 | 82 percentage of participants |
| Gardasil Vaccine Administration | Percentage of Participants Who Seroconverted to HPV Types 31, 33, 45, or 58 | HPV33 | 56 percentage of participants |
| Gardasil Vaccine Administration | Percentage of Participants Who Seroconverted to HPV Types 31, 33, 45, or 58 | HPV45 | 42 percentage of participants |
| Gardasil Vaccine Administration | Percentage of Participants Who Seroconverted to HPV Types 31, 33, 45, or 58 | HPV58 | 69 percentage of participants |
| Placebo Administration | Percentage of Participants Who Seroconverted to HPV Types 31, 33, 45, or 58 | HPV58 | 38 percentage of participants |
| Placebo Administration | Percentage of Participants Who Seroconverted to HPV Types 31, 33, 45, or 58 | HPV31 | 39 percentage of participants |
| Placebo Administration | Percentage of Participants Who Seroconverted to HPV Types 31, 33, 45, or 58 | HPV45 | 19 percentage of participants |
| Placebo Administration | Percentage of Participants Who Seroconverted to HPV Types 31, 33, 45, or 58 | HPV33 | 34 percentage of participants |
Secondary
Percentage of Participants Who Were Seropositive by HPV Type
Percentage of participants who were seropositive to HPV at enrollment, by specific HPV type.
Time frame: At Enrollment - 5 Month Enrollment Period
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gardasil Vaccine Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV16 | 32 percentage of participants |
| Gardasil Vaccine Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV33 | 25 percentage of participants |
| Gardasil Vaccine Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV11 | 45 percentage of participants |
| Gardasil Vaccine Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV45 | 15 percentage of participants |
| Gardasil Vaccine Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV6 | 73 percentage of participants |
| Gardasil Vaccine Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV52 | 36 percentage of participants |
| Gardasil Vaccine Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV31 | 31 percentage of participants |
| Gardasil Vaccine Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV58 | 36 percentage of participants |
| Gardasil Vaccine Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV18 | 46 percentage of participants |
| Placebo Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV58 | 36 percentage of participants |
| Placebo Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV6 | 73 percentage of participants |
| Placebo Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV11 | 47 percentage of participants |
| Placebo Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV16 | 37 percentage of participants |
| Placebo Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV18 | 41 percentage of participants |
| Placebo Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV31 | 38 percentage of participants |
| Placebo Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV33 | 30 percentage of participants |
| Placebo Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV45 | 18 percentage of participants |
| Placebo Administration | Percentage of Participants Who Were Seropositive by HPV Type | HPV52 | 35 percentage of participants |
Secondary
Study Compliance Rate
Percentage of participants to complete the 3-dose vaccination series and all 4 study visits.
Time frame: 18 Months
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil Vaccine Administration | Study Compliance Rate | 91.5 percentage of participants |
| Placebo Administration | Study Compliance Rate | 87.5 percentage of participants |