Safety and Immunogenicity of Extended 2-dose Regimens of 9-valent Human Papillomavirus (9vHPV) Vaccine (V503-069)

Study Overview
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Brief Summary
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This is a 96-month safety and immunogenicity study conducted in boys and girls 9 to 14 years of age and in young women 16 to 26 years of age. From this study, the goal is to establish that the investigational extended 2-dose regimens (0, 12 months; 0, 24 months; 0, 36 months; and 0, 60 months) studied in boys and girls 9 to 14 years of age are generally safe and immunogenic, with an antibody response that is not inferior to that observed in young women 16 to 26 years of age who receive the standard 3-dose regimen of 9-valent human papillomavirus (9vHPV) vaccine at 0, 2, and 6 months (i.e., the population and dose regimen used to establish 9vHPV vaccine efficacy).

Official Title
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A Phase 3 International, Multicenter, Open-label Study to Evaluate the Safety and Immunogenicity of 9vHPV Vaccine Administered as 2-dose Regimen With Extended Dosing Intervals in 9- to 14-Year Old Boys and Girls Compared With a Standard 3-dose Regimen in 16- to 26-Year Old Women

Conditions
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Papillomavirus Infections

Intervention / Treatment
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* Biological: 9vHPV vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Boys and Girls 9 to 15 Years: - Must not have had coitarche and does not plan on becoming sexually active during the vaccination period Women 16 to 26 Years: Has never had a Papanicolaou (Pap) test or only had normal Pap test results A lifetime history of 0 to 4 male and/or female sexual partners Cohort 0 Participants: - Received 1 dose of 9vHPV vaccine at least 1 year prior to enrollment and did not receive a second dose of any HPV vaccine Exclusion Criteria: All Participants: Known allergy to any vaccine component History of severe allergic reaction that required medical intervention Thrombocytopenia or any coagulation disorder Females only: participant is pregnant or expecting to donate eggs during day 1 through month 7 Currently immunocompromised, or been diagnosed with immunodeficiency Had a splenectomy Receiving or has received immunosuppressive therapies within the last year Received any immunoglobulin product or blood-derived product within 3 months Has received more than 1 dose of an HPV vaccine (Cohort 0) Received a marketed HPV vaccine or has participated in an HPV vaccine clinical trial (Cohorts 1-5)

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 26 Years

Sexes Eligible for Study
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All

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 4: 2 Doses of 9vHPV Vaccine Given 60 Months Apart<br>9 to 10 year old girls and boys receive a 2-dose regimen of 9vHPV vaccine at Day 1 and Month 60. | Biological: 9vHPV vaccine<br>* 9-valent human papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection<br>|
| Active Comparator: Cohort 5: 3 Doses of 9vHPV Vaccine Given Over a 6-Month Period<br>16 to 26 year old young women receive 3 dose regimen of 9vHPV vaccine at Day 1, Month 2 and Month 6. | Biological: 9vHPV vaccine<br>* 9-valent human papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection<br>|
| Experimental: Cohort 0: 1 Dose of 9vHPV Vaccine (previous 1-dose recipients)<br>10 to 15 year old girls and boys (who previously received 1 dose of 9vHPV vaccine) receive a second dose of 9vHPV vaccine at Day 1. | Biological: 9vHPV vaccine<br>* 9-valent human papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection<br>|
| Experimental: Cohort 1: 2 Doses of 9vHPV Vaccine Given 12 Months Apart<br>9 to 14 year old girls and boys receive a 2-dose regimen of 9vHPV vaccine at Day 1 and Month 12. | Biological: 9vHPV vaccine<br>* 9-valent human papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection<br>|
| Experimental: Cohort 2: 2 Doses of 9vHPV Vaccine Given 24 Months Apart<br>9 to 13 year old girls and boys receive a 2-dose regimen of 9vHPV vaccine at Day 1 and Months 24. | Biological: 9vHPV vaccine<br>* 9-valent human papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection<br>|
| Experimental: Cohort 3: 2 Doses of 9vHPV Vaccine Given 36 Months Apart<br>9 to 12 year old girls and boys receive a 2-dose regimen of 9vHPV vaccine at Day 1 and Month 36. | Biological: 9vHPV vaccine<br>* 9-valent human papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers of Anti-Human Papilloma Virus Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 as Measured by Competitive Luminex Immunoassay | Serum antibody titers for human papilloma virus (HPV) types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using competitive luminex immunoassay (cLIA). The geometric mean titer (GMT) for each HPV type will be reported in milli Merck units/mL (mMU/mL). | 4 weeks post last vaccination (Up to  Month 61) | 
| Percentage of Participants With at Least 1 Solicited Injection-site Adverse Event | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants with injection-site AEs (erythema/redness, pain and swelling) will be assessed. | Up to 5 days post vaccination | 
| Percentage of Participants With at Least 1 Systemic Adverse Event | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants with a systemic AE will be assessed. | Up to 15 days post vaccination | 
| Percentage of Participants With at Least 1 Serious Vaccine-Related Adverse Event | A serious adverse event (SAE) is defined as one that results in death, is life threatening, or requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or other important medical event that may require medical intervention. An SAE that is judged by the investigator to be related to the study vaccine is defined as a vaccine-related SAE. | Entire study period (Up to  Month 96) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants (Cohorts 1 to 5) Who Are Seropositive for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 | Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using cLIA. The percentage of participants who are seropositive (analysis population Cohorts 1 through 5 only) for each HPV type will be assessed. | 4 weeks post last vaccination | 
| Geometric Mean Titers (Cohorts 1 to 5) of Anti HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 | Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using cLIA. The GMT for each HPV type (analysis population Cohorts 1 through 5 only) will be reported in mMU/mL. | 12 months post last vaccination | 
| Percentage of Participants (Cohorts 1 to 5) Who Are Seropositive for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 | Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using cLIA. The percentage of participants who are seropositive (analysis population Cohorts 1 through 5 only) for each HPV type will be assessed. | 12 months post last vaccination | 
| Geometric Mean Titers ( Cohorts 1 to 5) of Anti HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 | Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using cLIA. The GMT for each HPV type (analysis population Cohorts 1 through 5 only) will be reported in mMU/mL. | 24 months post last vaccination | 
| Percentage of Participants (Cohorts 1 to 5) Who Are Seropositive for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 | Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using cLIA. The percentage of participants who are seropositive (analysis population Cohorts 1 through 5 only) for each HPV type will be assessed. | 24 months post last vaccination | 
| Geometric Mean Titers ( Cohorts 1 to 5) of Anti HPV Types 6, 11, 16, 18, 31, 33, 45, 52 , and 58 | Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using cLIA. The GMT for each HPV type (analysis population Cohorts 1 through 5 only) will be reported in mMU/mL. | 36 months post last vaccination | 
| Percentage of Participants (Cohorts 1 to 5) Who Are Seropositive for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 | Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using cLIA. The percentage of participants who are seropositive (analysis population Cohorts 1 through 5 only) for each HPV type will be assessed. | 36 months post last vaccination |