Prevention of Human Papillomavirus (HPV) in 20 to 45 Year Old Chinese Women (V501-041)

• ClinicalTrials.gov Identifier: NCT00834106
• Recruitment Status: Completed
• First Posted: February 3, 2009
• Results First Posted: October 12, 2017
• Last Update Posted: February 4, 2019
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

A study to test the safety and effectiveness of Quadrivalent HPV (types 6, 11, 16, 18) L1 VLP vaccine against combined incidence of HPV 6/11/16/18-related persistent infection and vaccine type-specific genital disease among Chinese females between the ages of 20 and 45.

Condition or disease	Intervention/treatment	Phase
HPV Infections	Biological: Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine; Biological: Comparator: placebo (unspecified)	Phase 3

Detailed Description:

The Base Study V501-041 duration was 30 months. The study was extended to further evaluate the efficacy of Quadrivalent HPV (Type 6, 11, 16, 18) L1 VLP (qHPV) vaccine against Cervical Intraepithelial Neoplasia Grade 2 (CIN 2), CIN 3, Adenocarcinoma In Situ (AIS), and/or cervical cancer. The efficacy was followed through the Month 78 visit, and the close-out visit was conducted at approximately Month 90 with only safety data collected

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3006 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Randomized, Placebo-Controlled, Double-Blind Study of Quadrivalent HPV (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) Vaccine to Investigate the Safety, and Efficacy in Chinese 20 - to 45-Years-Old Women
• Actual Study Start Date: December 31, 2008
• Actual Primary Completion Date: May 11, 2012
• Actual Study Completion Date: September 30, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: qHPV; Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine administered by intramuscular injection on Day 1, Month 2, and Month 6	Biological: Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine; Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine injection at Day 1, Month 2, and Month 6.; Other Names: Gardasil ™; V501
Placebo Comparator: Placebo; Placebo administered by intramuscular injection on Day 1, Month 2, and Month 6	Biological: Comparator: placebo (unspecified); Aluminum-containing Vaccine placebo injection at Day 1, Month 2, and Month 6.

Outcome Measures

Primary Outcome Measures :

1. Base Study: Combined Incidence of 6-Month Persistent Infection, Cervical Intraepithelial Neoplasia (CIN+), and External Genital Lesions Related to Human Papillomavirus (HPV) Type 6, 11, 16, or 18 in 20 to 45 Year Old Participants (Test of Hypothesis) [ Time Frame: From Day 1 until >=25 cases accumulate, up to Month 30 ]
   The endpoint included pathology panel consensus diagnosis of 6-month persistent infection, CIN+ (including CIN grade 1, 2, or 3, cervical adenocarcinoma in situ (AIS), and cervical cancer), or external genital lesions related to HPV Types 6, 11, 16, or 18 detected by polymerase chain reaction (PCR) in an adjacent section from the same tissue block.
2. Base Study: Combined Incidence of 6-Month Persistent Infection, CIN+, and External Genital Lesions Related to Human Papillomavirus (HPV) Type 6, 11, 16, or 18 in 20 to 26 Years Old Participants (Test of Hypothesis) [ Time Frame: From Day 1 until >=17 cases accumulate, up to Month 30 ]
   The endpoint included pathology panel consensus diagnosis of 6-month persistent infection, CIN+ (including CIN grade 1, 2, or 3, cervical adenocarcinoma in situ (AIS), and cervical cancer), or external genital lesions related to HPV Types 6, 11, 16, or 18 detected by PCR in an adjacent section from the same tissue block.
3. Entire Study: Combined Incidence of CIN2+ Related to HPV Types 16 or 18 in 20 to 45 Year Old Participants (End of Study Test of Hypothesis) [ Time Frame: Up to Month 78 ]
   The endpoint included pathology panel consensus diagnosis of CIN2+ (including CIN grade 2 or 3, AIS, and cervical cancer) related to HPV Types 16 or 18 detected by PCR in an adjacent section from the same tissue block.
4. Base Study: Percentage of Participants With One or More Solicited Injection-site Adverse Events [ Time Frame: Up to 15 days after any vaccination ]
   An adverse event (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 sponsor's product, 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 sponsor's product, is also an AE. Injection-site AEs were prompted on the Vaccination Report Card (VRC), which was completed by the participant for 15 days after each vaccination.
5. Base Study: Percentage of Participants With One or More Systemic Adverse Events [ Time Frame: Up to 15 days after any vaccination ]
   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 sponsor's product, 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 sponsor's product, is also an AE.
6. Base Study: Percentage of Participants Discontinued From Study Vaccination Due to an Adverse Event [ Time Frame: Up to 6 months ]
   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 sponsor's product, 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 sponsor's product, is also an AE.
7. Entire Study: Percentage of Participants With One or More Vaccine-related Serious Adverse Events [ Time Frame: Up to approximately 90 months ]
   A serious adverse event (SAE) is an AE 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 an overdose or, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention. Related SAEs were those deemed possibly, probably, or definitely related to study vaccine or a study procedure.
8. Entire Study: Percentage of Participants Who Died [ Time Frame: Up to approximately 90 months ]
   The percentage of participants who died on study due to any cause, whether or not related to the investigational product, were reported for each arm

Secondary Outcome Measures :

1. Entire Study: Combined Incidence of 12-Month Persistent Infection, CIN+, and External Genital Lesions Related to Human Papillomavirus (HPV) Type 6, 11, 16, or 18 in 20 to 45 Year Old Participants (End of Study Update) [ Time Frame: Up to 78 months ]
   The endpoint included pathology panel consensus diagnosis of 12-month persistent infection, CIN+ (including CIN grade 1, 2, or 3, cervical adenocarcinoma in situ (AIS), and cervical cancer), or external genital lesions related to HPV Types 6, 11, 16, or 18 detected by PCR in an adjacent section from the same tissue block.
2. Entire Study: Combined Incidence of 12-Month Persistent Infection, CIN+, and External Genital Lesions Related to Human Papillomavirus (HPV) Type 6, 11, 16, or 18 in 20 to 26 Year Old Participants (End of Study Update) [ Time Frame: Up to 78 months ]
   The endpoint included pathology panel consensus diagnosis of 12-month persistent infection, CIN+ (including CIN grade 1, 2, or 3, cervical adenocarcinoma in situ (AIS), and cervical cancer), or external genital lesions related to HPV Types 6, 11, 16, or 18 detected by PCR in an adjacent section from the same tissue block.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Healthy women between the ages of 20 and 45
• Have used effective contraception for 2 weeks prior to starting in the study
• Does not have a temperature within 24 hours before the first injection

Exclusion Criteria:

• Prior history of genital warts
• More than 4 lifetime sexual partners
• Have undergone hysterectomy
• Have active cervical disease or history of cervical disease

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

More Information

Publications:

Wei L, Xie X, Liu J, Zhao Y, Chen W, Zhao C, Wang S, Liao X, Shou Q, Qiu Y, Qiao Y, Saah AJ. Efficacy of quadrivalent human papillomavirus vaccine against persistent infection and genital disease in Chinese women: A randomized, placebo-controlled trial with 78-month follow-up. Vaccine. 2019 Jun 12;37(27):3617-3624. doi: 10.1016/j.vaccine.2018.08.009. Epub 2018 Aug 16.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chen W, Zhao Y, Xie X, Liu J, Li J, Zhao C, Wang S, Liao X, Shou Q, Zheng M, Saah AJ, Wei L, Qiao Y. Safety of a quadrivalent human papillomavirus vaccine in a Phase 3, randomized, double-blind, placebo-controlled clinical trial among Chinese women during 90 months of follow-up. Vaccine. 2019 Feb 4;37(6):889-897. doi: 10.1016/j.vaccine.2018.12.030. Epub 2019 Jan 9.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT00834106
• Other Study ID Numbers: V501-041; 2009_532
• First Posted: February 3, 2009
• Results First Posted: October 12, 2017
• Last Update Posted: February 4, 2019
• Last Verified: January 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Merck Sharp & Dohme Corp.:

HPV 6/11/16/18 Infection

Additional relevant MeSH terms:

Papillomavirus Infections; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections