Immunogenicity and Tolerability of Broad Spectrum Human Papillomavirus (HPV) Vaccine in Adult and Young Adult Women (V503-004)

An Open-Label Phase III Clinical Trial to Study the Immunogenicity and Tolerability of GARDASIL®9 (A Multivalent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] Vaccine) in Adult Women (27- to 45-Year-Olds) Compared to Young Adult Women (16 to 26 Year Olds)

This study will assess the safety and immunogenicity of GARDASIL®9 (V503) in 16- to 45-year-old women. The primary hypothesis of the study states that anti-HPV 16, 18, 31, 33, 45, 52, and 58 geometric mean titers (GMTs) at 4 weeks postdose 3 are non-inferior in adult women as compared with GMTs in young adult women.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer; Vulvar Cancer; Vaginal Cancer; Human Papillomavirus Infection; Genital Warts
• Intervention / Treatment: Biological: V503

• Study Type: Interventional
• Enrollment (Actual): 1212
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
    • Universitatsklinik fuer Frauenheilkunde und Geburtshilfe ( Site 0002)
  • Wien, Austria
    • Klin. Abtlg. fuer Gynaekologie und Geburtshilfe ( Site 0001)
• Belgium
  • Edegem, Belgium
    • Universitair Ziekenhuis Antwerpen ( Site 0007)
  • Gent, Belgium
    • Universitair Ziekenhuis Gent ( Site 0006)
  • Leuven, Belgium
    • Universitair Ziekenhuis Gasthuisberg ( Site 0005)
  • Wilrijk, Belgium
    • University of Antwerp ( Site 0004)
• Finland
  • Helsinki, Finland
    • HUS Katiloopiston sairaala ( Site 0009)
  • Helsinki, Finland
    • Ita-Helsingin Rokotetutkimuskeskus ( Site 0011)
  • Pori, Finland
    • Porin Rokotetutkimusklinikka ( Site 0012)
  • Tampere, Finland
    • Tampereen yliopisto - Tampereen rokotetutkimusklinikka ( Site 0010)
  • Turku, Finland
    • Turun rokotetutkimusklinikka ( Site 0037)
• Germany
  • Berlin, Germany
    • Universitaetsmedizin Berlin Charite ( Site 0016)
  • Dusseldorf, Germany
    • Universitaetsklinikum Duesseldorf ( Site 0014)
  • Hamburg, Germany
    • Praxis Dr. Peters ( Site 0015)
  • Hamburg, Germany
    • Universitaetsklinikum Hamburg-Eppendorf ( Site 0017)
  • Tuebingen, Germany
    • Universitaetsklinikum Tuebingen ( Site 0013)
• Italy
  • Milano, Italy
    • Ospedale San Raffaele ( Site 0022)
  • Palermo, Italy
    • Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello ( Site 0023)
  • Milan
    • Milano, Milan, Italy
      • Istituto Nazionale dei tumori ( Site 0020)
• Spain
  • Almeria, Spain
    • Complejo Hospitalario de Torrecardenas ( Site 0030)
  • Hospitalet de Llobregat, Spain
    • Institut Catala Oncologia de Bellvitge - ICO ( Site 0026)
  • Madrid, Spain
    • Hospital Sanitas La Moraleja ( Site 0031)
  • Madrid, Spain
    • Hospital Universitario Infanta Leonor ( Site 0028)
  • Barcelona
    • Centelles, Barcelona, Spain
      • CAP Centelles ( Site 0027)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• good physical health

Exclusion Criteria:

• history of an abnormal Pap (Papanicolaou) test or abnormal cervical biopsy results
• history of HPV-related condition
• history of known prior vaccination with an HPV vaccine
• pregnant
• user of recreational or illicit drugs
• history of severe allergic reaction, including known allergy to any vaccine component
• immunocompromised
• history of certain medications or is currently taking or has taken certain medications (details will be discussed at the time of consent)
• has thrombocytopenia or other coagulation disorder
• concurrently enrolled in a clinical study of investigational agent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adult Women 27- to 45-years Old; Adult women 27- to 45-years old will receive V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.	Biological: V503; V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6; Other Names: GARDASIL®9 (HPV 9-valent vaccine [recombinant, adsorbed]); HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58
Active Comparator: Young Adult Women 16- to 26-years Old; Young adult women 16- to 26-years old will receive V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.	Biological: V503; V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6; Other Names: GARDASIL®9 (HPV 9-valent vaccine [recombinant, adsorbed]); HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type	Antibodies to the HPV types contained in V503 were measured using a competitive luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). Statistical comparisons between arms was performed for the HPV types considered oncogenic (HPV Types 16/18/31/33/45/52/58).	4 weeks post vaccination 3 (Month 7)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants That Experienced at Least 1 Adverse Event (AE)	An AE is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The percentage of participants with 1 or more AEs was assessed.	Up to 1 month post vaccination 3 (up to 7 months)
Percentage of Participants Who Had Study Vaccine Discontinued Due to Adverse Event.	An adverse event is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The percentage of participants who discontinued the study vaccine due to an adverse event regardless of study completion status was assessed.	Up to 1 month post vaccination 3 (up to 7 months)
Percentage of Participants With at Least 1 Solicited Injection-site Adverse Event	Participants were asked to record any injection-site reactions prompted in the Vaccination Report Card, i.e., injection-site tenderness, swelling, or redness, occurring after each study vaccination (solicited injection-site reactions). The percentage of participants with 1 or more solicited injection-site AE was assessed.	Up to 5 days post any vaccination
Percentage of Participants That Reported at Least 1 Systemic Adverse Event	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. Systemic AEs are those not categorized as injection-site AEs. The percentage of participants that reported at least 1 systemic AE was assessed	Up to 15 days post any vaccination
Percentage of Participants With Elevated Temperature (Fever)	Participants were asked to record oral body temperature in the Vaccination Report Card. The percentage of participants with elevated temperature (≥37.8°C or 100.0°F) was assessed.	Up to 5 days post any vaccination
Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types	Antibodies to the HPV types contained in V503 were measured using a competitive luminex immunoassay. The percentage of participants who were seronegative on Day 1 and have anti-HPV titer greater or equal to the type-specific serostatus cutoff at 4 weeks postdose 3 was assessed.	4 weeks post vaccination 3 (Month 7)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Joura EA, Ulied A, Vandermeulen C, Rua Figueroa M, Seppa I, Hernandez Aguado JJ, Ahonen A, Reich O, Virta M, Perino A, Peris Tuser M, Peters K, Origoni M, Raspagliesi F, Tjalma WAA, Tummers P, Woelber L, Nieminen P, van Damme P, Sehouli J, Fiol Ruiz G, Brucker S, Fehm T, Cheon K, Rawat S, Luxembourg A, Wittke F. Immunogenicity and safety of a nine-valent human papillomavirus vaccine in women 27-45 years of age compared to women 16-26 years of age: An open-label phase 3 study. Vaccine. 2021 May 12;39(20):2800-2809. doi: 10.1016/j.vaccine.2021.01.074. Epub 2021 Mar 3.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2017
• Primary Completion (Actual): November 19, 2018
• Study Completion (Actual): November 19, 2018

Study Registration Dates

• First Submitted: May 16, 2017
• First Submitted That Met QC Criteria: May 16, 2017
• First Posted (Actual): May 18, 2017

Study Record Updates

• Last Update Posted (Actual): November 21, 2019
• Last Update Submitted That Met QC Criteria: November 4, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Virus Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; DNA Virus Infections; Skin Diseases, Infectious; Warts; Skin Diseases, Viral; Tumor Virus Infections; Vaginal Diseases; Vulvar Diseases; Vulvar Neoplasms; Papillomavirus Infections; Vaginal Neoplasms; Condylomata Acuminata; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: V503-004

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