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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Papillomavirus Infections
• Intervention / Treatment: Biological: 9vHPV vaccine

• Study Type: Interventional
• Enrollment (Estimated): 700
• Phase: Phase 3

Contacts and Locations

Study Locations

• Colombia
  • Antioquia
    • Medellín, Antioquia, Colombia, 050021
      • Fundación Centro de Investigación Clínica CIC ( Site 0157)
  • Cundinamarca
    • Chia, Cundinamarca, Colombia, 250001
      • Centro de Atención e Investigación Médica SAS - CAIMED CHIA ( Site 0151)
• Mexico
  • Distrito Federal
    • Mexico City, Distrito Federal, Mexico, 06760
      • CAIMED México ( Site 0207)
  • Michoacan
    • Morelia, Michoacan, Mexico, 58350
      • AINPAD ( Site 0204)
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Unidad biomedica avanzada monterrey ( Site 0203)
  • Yucatan
    • Merida, Yucatan, Mexico, 97130
      • Centro Multidisciplinario para el Desarrollo Especializado de la Investigacion Clinica en Yucatan (
• Poland
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-369
      • Uniwersytecki Szpital Kliniczny-Klinika Pediatrii i Chorob Infekcyjnych ( Site 0556)
  • Lodzkie
    • Lodz, Lodzkie, Poland, 91-347
      • Gravita Diagnostyka i Leczenie Nieplodnosci ( Site 0555)
  • Malopolskie
    • Tarnow, Malopolskie, Poland, 33-100
      • ALERGO-MED Specjalistyczna Przychodnia Lekarska ( Site 0557)
  • Podkarpackie
    • Debica, Podkarpackie, Poland, 39-200
      • Jerzy Brzostek Prywatny Gabinet Lekarski ( Site 0553)
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1864
      • Perinatal HIV Research Unit_Do not use - Duplicate facility ( Site 0351)
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7500
      • TREAD Research ( Site 0354)
    • Cape Town, Western Cape, South Africa, 7795
      • Desmond Tutu HIV Foundation ( Site 0355)
• Taiwan
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital ( Site 0653)
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital ( Site 0651)
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation.Linkou Branch ( Site 0652)
• United States
  • California
    • Daly City, California, United States, 94015
      • Kaiser Permanente Daly City ( Site 0044)
    • Oakland, California, United States, 94611
      • Kaiser Permanente Oakland ( Site 0020)
    • Roseville, California, United States, 95661
      • Kaiser Permanente Roseville ( Site 0047)
    • Sacramento, California, United States, 95815
      • Kaiser Permanente Sacramento ( Site 0043)
    • Sacramento, California, United States, 95823
      • Kaiser Permanente South Sacramento ( Site 0045)
    • San Jose, California, United States, 95119
      • Kaiser Permanente San Jose ( Site 0046)
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Santa Clara ( Site 0042)
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research ( Site 0022)
  • Florida
    • Naples, Florida, United States, 34102
      • Advanced Research for Health Improvement, LLC-Pediatrics ( Site 0007)
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Tribe Clinical Research, LLC ( Site 0010)
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center ( Site 0032)
  • Texas
    • Corpus Christi, Texas, United States, 78413
      • Coastal Bend Clinical Research ( Site 0025)
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch-Sealy Institute for Vaccine Sciences Clinical Trials Program ( Si
  • Washington
    • Cheney, Washington, United States, 99004
      • MultiCare Rockwood Cheney Clinic ( Site 0038)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 26 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 0: 1 Dose of 9vHPV Vaccine (previous 1-dose recipients); 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; 9-valent human papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection
Experimental: Cohort 1: 2 Doses of 9vHPV Vaccine Given 12 Months Apart; 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; 9-valent human papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection
Experimental: Cohort 2: 2 Doses of 9vHPV Vaccine Given 24 Months Apart; 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; 9-valent human papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection
Experimental: Cohort 3: 2 Doses of 9vHPV Vaccine Given 36 Months Apart; 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; 9-valent human papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection
Experimental: Cohort 4: 2 Doses of 9vHPV Vaccine Given 60 Months Apart; 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; 9-valent human papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection
Active Comparator: Cohort 5: 3 Doses of 9vHPV Vaccine Given Over a 6-Month Period; 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; 9-valent human papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Teppler H, Bautista O; Thomas Group; Flores S, McCauley J, Luxembourg A. Design of a Phase III immunogenicity and safety study evaluating two-dose regimens of 9-valent human papillomavirus (9vHPV) vaccine with extended dosing intervals. Contemp Clin Trials. 2021 Jun;105:106403. doi: 10.1016/j.cct.2021.106403. Epub 2021 Apr 12.

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2021
• Primary Completion (Estimated): June 18, 2029
• Study Completion (Estimated): June 18, 2029

Study Registration Dates

• First Submitted: January 12, 2021
• First Submitted That Met QC Criteria: January 12, 2021
• First Posted (Actual): January 13, 2021

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Disease Attributes; DNA Virus Infections; Tumor Virus Infections; Urogenital Diseases; Genital Diseases; Papillomavirus Infections
• Other Study ID Numbers: V503-069 (Other Identifier: Merck); 2022-500253-37-00 (Other Identifier: EU CT); 2020-003736-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No