Immunobridging Study of 9- Valent Human Papillomavirus (9vHPV) Vaccine (V503) in Chinese Females 9 to 45 Years of Age (V503-024)

Merck Sharp & Dohme LLC1,990 enrolled

Overview

This study will investigate the immunogenicity and safety of the 9vHPV vaccine in healthy Chinese females 9 to 45 years of age. The study consists of Stage I (Day 1 to Month 7) and Stage II (post Month 7 to Month 60). Stage II will report the long-term immunogenicity and safety in the 9-19 year-old age group only. The dual-primary hypotheses of Stage I are that 9vHPV vaccine induces non-inferior immune responses in females 9 to 19 years of age who are seronegative at Day 1 to the relevant HPV type compared to females 20 to 26 years of age who are seronegative at Day 1 to the relevant HPV type, as measured by anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 GMTs at 1 month post Dose 3, and 9vHPV vaccine induces non-inferior immune responses in females 27 to 45 years of age who are seronegative at Day 1 to the relevant HPV type compared to females 20 to 26 years of age who are seronegative at Day 1 to the relevant HPV type, as measured by the seroconversion percentages to each of HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at 1 month post Dose 3. (Each vaccine component will be analyzed separately.)

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

1,990

Conditions

Papillomavirus Infections

Interventions

0.5 mL 9vHPV VLP Vaccine

Eligibility

Sex: FEMALEMin age: 9 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria * Participant is a Chinese female judged to be in good physical health based on medical history and physical examination * Not a woman of childbearing potential (WOCBP) or if of WOCBP, has not had sex with males or has had sex with males and used effective contraception as defined in Appendix 2 since the first day of participant's last menstrual period through Day 1. And the participant understands and agrees that during the Day 1 through Month 7 period, she should not have sexual intercourse with males without effective contraception, and that the use of the rhythm method, withdrawal, and emergency contraception are not acceptable methods * Has a lifetime history of 0 to 4 male and/or female sexual partners at the time of enrollment. Male partner is defined as someone with whom the participant has penile penetrative sexual intercourse. Female partner is defined as someone who has contacted, either by penetrative (with fingers or other objects) or non-penetrative means, the participant's genitalia during sexual activity Exclusion Criteria * Known allergy to any vaccine component, including aluminum, yeast, or BENZONASE™ (nuclease, Nycomed™). An allergy to vaccine components is defined as an allergic reaction that met the criteria for serious adverse event * History of severe allergic reaction (e.g. swelling of the mouth and throat, difficulty breathing, hypotension, or shock) that required medical intervention * Known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections * Has a fever (defined as an axillary temperature ≥37.1°C) within 24 hours prior to the Day 1 vaccination * Has any history of abnormal Pap test showing squamous intraepithelial lesion (SIL) or atypical squamous cells - undetermined significance (ASC-US), atypical squamous cells - cannot exclude HSIL (ASC-H), atypical glandular cells, or biopsy showing cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ or cervical cancer * History of external genital wart, vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), vulvar cancer or vaginal cancer * History of a positive test for HPV * Currently immunocompromised or has been diagnosed as having congenital or acquired immunodeficiency, human immunodeficiency virus (HIV) infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease, or other autoimmune condition * History of splenectomy * Donated blood within 1 week prior to the Day 1 vaccination, or intends to donate during Day 1 through Month 7 of the study * Expecting to donate eggs during Day 1 through Month 7 of the study * Pregnant * Receiving or has received in the year prior to Day 1 vaccination the following immunosuppressive therapies: radiation therapy, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporin, leflunomide (Arava™), tumor necrosis factor (TNF)-α antagonists, monoclonal antibody therapies (including rituximab \[Rituxan™\]), intravenous gamma globulin (IVIG), antilymphocyte sera, or other therapy known to interfere with the immune response. With regard to systemic corticosteroids, a participant will be excluded if she is currently receiving steroid therapy, has recently (defined as within 2 weeks of Day 1 vaccination) received such therapy, or has received 2 or more courses of corticosteroids (orally or parenterally) lasting at least 1 week in duration in the year prior to Day 1 vaccination. Participants using inhaled, nasal or topical corticosteroids are considered eligible for the study * Has received immune globulin product (including RhoGAM™ or blood-derived product other than IVIG within 6 months prior to Day 1 vaccination, or plans to receive any such product during Day 1 through Month 7 of the study * Has received a marketed HPV vaccine, or has participated in an HPV vaccine clinical trial and has received either active agent or placebo * Has received inactivated or recombinant vaccines within 14 days prior to Day 1 vaccination or has received live vaccines within 21 days prior to Day 1 vaccination * Concurrently enrolled in clinical studies of interventional agents * a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence. Alcohol abusers are defined as those who drink despite recurrent social, interpersonal, and/or legal problems as a result of alcohol use

Locations (2)

Kaihua country Center for Disease Control and Prevention ( Site 0002)

Quzhou, Zhejiang, China

Shaoxing keqiao center for disease prevention and control ( Site 0001)

Shaoxing, Zhejiang, China

Outcomes

Primary Outcomes

Stage I: Competitive Luminex Immunoassay (cLIA) GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age and 20 to 26 Years of Age: Month 7

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 will be reported in mMU/mL.

Time frame: 1 month post vaccination 3 (Month 7)

Stage I: Percentage of Participants 27 to 45 Years of Age and 20 to 26 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using cLIA and will be reported in mMU/mL. The percentage of participants who are seropositive for each HPV type will be summarized.

Time frame: 1 month post vaccination 3 (Month 7)

Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age: Month 12

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 will be reported in mMU/mL.

Time frame: Month 12

Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month24

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 will be reported in mMU/mL.

Time frame: Month 24

Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 36

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 will be reported in mMU/mL.

Time frame: Month 36

Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 48

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 will be reported in mMU/mL.

Time frame: Month 48

Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 60

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 will be reported in mMU/mL.

Time frame: Month 60

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 12

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will determined using cLIA. The percentage of participants who are seropositive for each HPV type will be summarized.

Time frame: Month 12

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 24

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will determined using cLIA. The percentage of participants who are seropositive for each HPV type will be summarized.

Time frame: Month 24

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 36

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will determined using cLIA. The percentage of participants who are seropositive for each HPV type will be summarized.

Time frame: Month 36

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 48

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will determined using cLIA. The percentage of participants who are seropositive for each HPV type will be summarized.

Time frame: Month 48

Stage II: Percentage of Participants 9 to 19 years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 60

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will determined using cLIA. The percentage of participants who are seropositive for each HPV type will be summarized.

Time frame: Month 60

Stage II: Immunoglobulin G Luminex Immunoassay (IgG LIA) GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 12

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using IgG LIA. The GMT for each HPV type will be reported in mMU/mL.

Time frame: Month 12

Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 24

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using IgG LIA. The GMT for each HPV type will be reported in mMU/mL.

Time frame: Month 24

Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 36

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using IgG LIA. The GMT for each HPV type will be reported in mMU/mL.

Time frame: Month 36

Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 48

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using IgG LIA. The GMT for each HPV type will be reported in mMU/mL.

Time frame: Month 48

Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 60

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using IgG LIA. The GMT for each HPV type will be reported in mMU/mL.

Time frame: Month 60

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 12

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using IgG LIA. The percentage of participants that achieve the serostatus cutoffs for seroconversion for each HPV type will be summarized.

Time frame: Month 12

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 24

Time frame: Month 24

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 36

Time frame: Month 36

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 48

Time frame: Month 48

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 60

Time frame: Month 60

Secondary Outcomes

Stage I: Percentage of Participants 9 to 19 Years of Age and 20 to 26 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using cLIA and are reported in mMU/mL. The percentage of participants who are seropositive for each HPV type will be summarized.

Time frame: 1 month post vaccination 3 (Month 7)

Stage I: cLIA GMTs for HPV Tys 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 15 Years of Age and 20 to 26 Years of Age: Month 7

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 will be reported in mMU/mL.

Time frame: 1 month post vaccination 3 (Month 7)

Stage I: Percentage of Participants 9 to 15 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

Time frame: 1 month post vaccination 3 (Month 7)

Stage I: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 27 to 45 Years of Age: Month 7

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 will be reported in mMU/mL.

Time frame: 1 month post vaccination 3 (Month 7)

Stage I: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age, 20 to 26 Years of Age, and 27 to 45 Years of Age: Month 7

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using IgG LIA. The GMT for each HPV type will be reported in mMU/mL.

Time frame: 1 month post vaccination 3 (Month 7)

Stage I: Percentage of Participants 9 to 19 Years of Age, 20 to 26 Years of Age, and 27 to 45 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

Data from ClinicalTrials.gov

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Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using IgG LIA and are reported in mMU/mL. The percentage of participants who are seropositive for each HPV type will be summarized.

Time frame: 1 month post vaccination 3 (Month 7)

Stage I: Percentage of Participants Who Experience at Least 1 Solicited Injection-site AE

An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. The participant or the parent/guardian of the participant were to record the presence of any vaccination report card (VRC)-prompted injection-site AEs that occurred in the 8 days after any vaccination. The percentage of participants with an injection-site AE prompted on the VRC (erythema, pain, swelling and induration) will be summarized.

Time frame: Up to 8 days post any vaccination

Stage I: Percentage of Participants Who Experience at Least 1 Systemic AE

An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. The percentage of participants with a systemic AE will be summarized.

Time frame: Up to 30 days post any vaccination

Stage I: Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE)

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the study vaccine. An SAE is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, or is another important medical event. The percentage of participants that experienced 1 or more SAEs will be summarized.

Time frame: Day 1 to Month 7

Stage I: Percentage of Participants with Elevated Axillary Temperature (≥37.1 C)

Participant or participant's legally acceptable representative will be asked to record axillary temperature in the evening after each study vaccination and daily, at the same time of day whenever possible, for 7 days after each study vaccination in the VRC. The percentage of participant's who had an axillary temperature ≥37.1°C will be summarized.

Time frame: up to 8 days post any vaccination

Stage II: Percentage of Participant 9 to 19 years of Age Who Experience at Least 1 Serious Adverse Event (SAE): Month 7 to Month 60

Time frame: Month 7 to Month 60