Immunogenicity and Tolerability of V503 Versus GARDASIL (V503-009)

A Randomized, Double-Blinded, Controlled With GARDASIL (Human Papillomavirus Vaccine [Types 6, 11, 16, 18] (Recombinant, Adsorbed)), Phase III Clinical Trial to Study the Immunogenicity and Tolerability of V503 (9-Valent Human Papillomavirus (HPV) Vaccine) in Preadolescent and Adolescent Girls (9- to 15-year-old)

Primary objective:

• To demonstrate that administration of V503 induces non-inferior Geometric Mean Titers (GMTs) (for serum anti-HPV16 and anti-HPV18) compared to GARDASIL.

Secondary objectives:

• To evaluate the tolerability of V503 in 9-15 year-old girls.
• To summarize humoral immune response (anti-HPV 6, 11, 16, 18) induced by V503 or GARDASIL.

Study Overview

• Status: Completed
• Conditions: Human Papillomavirus
• Intervention / Treatment: Biological: V503; Biological: GARDASIL

• Study Type: Interventional
• Enrollment (Actual): 600
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female from 9 to 15 years old.
• Good physical health.

Exclusion Criteria:

• Known allergy to any vaccine component.
• History of severe allergic reaction.
• Thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections.
• Pregnant subject.
• Immunocompromised or immunodeficient subject.
• Splenectomy.
• Receipt of medication / vaccine that may interfere with study assessment.
• Fever
• History of a positive test for HPV, prior receipt of HPV vaccine or prior participation to HPV trial.
• Any condition that might interfere with study assessment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: V503; 9-valent HPV [Types 6, 11, 16, 18, 31, 33, 45, 52, and 58] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	Biological: V503; 9-valent HPV [Types 6, 11, 16, 18, 31, 33, 45, 52, and 58] L1 virus-like particle vaccine; Other Names: 9vHPV vaccine
Active Comparator: GARDASIL; Quadrivalent HPV [Types 6, 11, 16, and 18] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	Biological: GARDASIL; Quadrivalent HPV [Types 6, 11, 16, and 18] L1 virus-like particle vaccine; Other Names: qHPV vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers (GMTs) to HPV Types 16 and 18	Serum antibodies to HPV types 16 and 18 were measured with a Competitive Luminex Immunoassay.	4 weeks postdose 3 (Month 7)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMTs to HPV Types 6 and 11	Serum antibodies to HPV types 6 and 11 were measured with a Competitive Luminex Immunoassay.	4 weeks postdose 3 (Month 7)
Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18	Serum antibodies to HPV types were measured with a Competitive Luminex Immunoassay. The serostatus cutoffs (milli Merck Units/mL) for HPV types were as follows: HPV Type 6: ≥30; HPV Type 11: ≥16; HPV Type 16: ≥20; HPV Type 18: ≥24. The percentage of participants who were seropositive according to these cutoffs was assessed.	4 weeks postdose 3 (Month 7)
Percentage of Participants With One or More Adverse Events	An adverse event is defined as any unfavourable 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 product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine, is also an adverse event. The percentage of participants with one or more adverse events was assessed.	Up to Month 7
Percentage of Participants With One or More Injection-site Adverse Reactions	The percentage of participants with one or more injection-site adverse reactions (solicited or unsolicited) was assessed.	Up to 5 days after any vaccination
Percentage of Participants With One or More Systemic Adverse Events	The percentage of participants with one or more systemic adverse events was assessed.	Up to 15 days after any vaccination
Percentage of Participants With Maximum Oral Temperature ≥37.8°C	The percentage of participants with maximum oral temperature ≥37.8°C was assessed.	Up to 15 days after any vaccination
Percentage of Participants With One or More Serious Adverse Events	A serious adverse event is an adverse event that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is a cancer, or may jeopardize the participant and may require medical or surgical intervention. The percentage of participants with one or more serious adverse events was assessed.	Up to Month 7

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Moreira ED Jr, Block SL, Ferris D, Giuliano AR, Iversen OE, Joura EA, Kosalaraksa P, Schilling A, Van Damme P, Bornstein J, Bosch FX, Pils S, Cuzick J, Garland SM, Huh W, Kjaer SK, Qi H, Hyatt D, Martin J, Moeller E, Ritter M, Baudin M, Luxembourg A. Safety Profile of the 9-Valent HPV Vaccine: A Combined Analysis of 7 Phase III Clinical Trials. Pediatrics. 2016 Aug;138(2):e20154387. doi: 10.1542/peds.2015-4387. Epub 2016 Jul 15.
• Vesikari T, Brodszki N, van Damme P, Diez-Domingo J, Icardi G, Petersen LK, Tran C, Thomas S, Luxembourg A, Baudin M. A Randomized, Double-Blind, Phase III Study of the Immunogenicity and Safety of a 9-Valent Human Papillomavirus L1 Virus-Like Particle Vaccine (V503) Versus Gardasil(R) in 9-15-Year-Old Girls. Pediatr Infect Dis J. 2015 Sep;34(9):992-8. doi: 10.1097/INF.0000000000000773.

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2011
• Primary Completion (Actual): December 20, 2011
• Study Completion (Actual): December 20, 2011

Study Registration Dates

• First Submitted: February 24, 2011
• First Submitted That Met QC Criteria: February 24, 2011
• First Posted (Estimate): February 25, 2011

Study Record Updates

• Last Update Posted (Actual): December 14, 2018
• Last Update Submitted That Met QC Criteria: November 26, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: V503-009; GDS01C (Other Identifier: MCMVaccBV (SPMSD) Protocol Number); 2010-023393-39 (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