A Study of the Safety, Tolerability, and Immunogenicity of a 9-valent Human Papillomavirus Vaccine ([9vHPV]; V503) Administered to 9- to 15-Year-Old Japanese Girls (V503-008).

A Phase III Open-label, Safety, Tolerability and Immunogenicity Study of a 9-Valent Human Papillomavirus (HPV) L1 Virus-Like Particle (VLP) Vaccine Administered to 9- to 15-Year-Old Japanese Preadolescent and Adolescent Girls

This study will evaluate the safety, tolerability, and immunogenicity of V503 in Japanese girls between the ages of 9 and 15 and will determine whether V503 induces an acceptable immune response to all human papillomavirus (HPV) strains contained in the vaccine. The success criterion for the primary analysis requires that point estimates for seroconversion rate be greater than 90% for all 9 HPV types.

Study Overview

• Status: Completed
• Conditions: Papillomavirus Infections
• Intervention / Treatment: Biological: V503

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 15 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Participant is in good physical health-
• Participant's parent/legal guardian is able to read, understand, and complete the vaccine report card
• Participant's parent/legal guardian agrees to provide a phone number for follow-up purposes
• Participant is not sexually active and does not plan to become sexually active during the time from Day 1 to Month 7 of the study

Exclusion Criteria:

• Participant has a history of severe allergic reaction that required medical intervention
• Participant has thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injection
• Participant is pregnant
• Participant intends to donate blood during the time from Day 1 to Month 7 of the study
• Participant is immunocompromised or has been diagnosed as having a congenital or acquired immunodeficiency, human immunodeficiency virus (HIV) infection, lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune condition.
• Participant has had a splenectomy
• Participant has received any of the following immunosuppressive therapies in the year prior to enrollment: radiation therapy, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporin, leflunomide (Arava), tumor necrosis factor alpha (TNF-α) antagonists, monoclonal antibody therapies, antilymphocyte sera, or other therapy known to interfere with the immune response.
• Participant has received any immune globulin product or blood-derived product in the three months prior to the Day 1 vaccination, or plans to receive any such product through Month 7 of the study
• Participant has received any inactivated vaccines within 14 days of the Day 1 vaccination or any live vaccines within 28 days of the Day 1 vaccination
• Participant has received a marketed HPV vaccine or has participated in an HPV vaccine clinical trial
• Participant has had a fever (oral temperature ≥37.8°C) within 24 hours of the Day 1 vaccination
• Participant has a history of a positive test for HPV or history of genital warts

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All Enrolled; 9-valent human papillomavirus (9vHPV) L1 VLP vaccine (V503), 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6.	Biological: V503; V503 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine	Serum antibody titers for HPV virus-like particles (VLPs), Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using competitive luminex immunoassay (cLIA). The serostatus cutoffs (milli Merck U/mL) for HPV types were as follows: HPV Type 6: ≥30, HPV Type 11: ≥16; HPV Type 16: ≥20, HPV Type 18: ≥24, HPV Type 31: ≥10, HPV Type 33: ≥8, HPV Type 45: ≥8, HPV Type 52: ≥8, and HPV Type 58: ≥8.	4 weeks post-vaccination 3 (Month 7)
Percentage of Participants With an Injection-site Adverse Event (AE)	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 vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. AEs such as redness, swelling, and pain/tenderness/soreness at the injection site were recorded.	up to 5 days after any vaccination
Percentage of Participants With a Non-Injection Site (Systemic) AE	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 vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Systemic AEs were those not categorized as injection-site AEs.	up to 15 days after any vaccination
Percentage of Participants With a Vaccine-related AE	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 vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Adverse experience that is judged by the Investigator to be "definitely related," "probably related," or "possibly related" to the study drug is defined as a vaccine-related AE.	up to 15 days after any vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers (GMTs) for Each of the HPV Types Contained in the Vaccine	Serum antibody titers for HPV virus-like particles (VLPs), Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using cLIA. Titers are reported in milli Merck Units/mL.	4 weeks post-vaccination 3 (Month 7)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Iwata S, Murata S, Rong Han S, Wakana A, Sawata M, Tanaka Y. Safety and Immunogenicity of a 9-Valent Human Papillomavirus Vaccine Administered to 9- to 15-Year-Old Japanese Girls. Jpn J Infect Dis. 2017 Jul 24;70(4):368-373. doi: 10.7883/yoken.JJID.2016.299. Epub 2016 Dec 22.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2011
• Primary Completion (Actual): August 10, 2013
• Study Completion (Actual): August 10, 2013

Study Registration Dates

• First Submitted: December 3, 2010
• First Submitted That Met QC Criteria: December 3, 2010
• First Posted (Estimate): December 6, 2010

Study Record Updates

• Last Update Posted (Actual): November 28, 2018
• Last Update Submitted That Met QC Criteria: October 30, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Papillomavirus vaccines; Uterine cervical cancer; Human Papilloma Virus infections
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Tumor Virus Infections; Papillomavirus Infections
• Other Study ID Numbers: V503-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis