search
Back to results

A Study to Evaluate the Immunogenicity, Safety and Tolerability of Quadrivalent Human Papillomavirus Vaccine (V501) in Chinese Girls Aged 9-19 Years and Young Women Aged 20-26 Years (V501-213)

Primary Purpose

Prevention of HPV Types 16- and 18-related Cervical Cancer, Cervical Intraepithelial Neoplasia (CIN) 1/2/3, and Cervical Adenocarcinoma in Situ

Status
Active
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
V501
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Prevention of HPV Types 16- and 18-related Cervical Cancer, Cervical Intraepithelial Neoplasia (CIN) 1/2/3, and Cervical Adenocarcinoma in Situ

Eligibility Criteria

9 Years - 26 Years (Child, Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Not pregnant and 1) not a woman of childbearing potential (WOCBP), or 2) a WOCBP who has not had sex with males or has had sex with males and used effective contraception since the first day of participant's last menstrual period through Day 1 and understands and agrees that during the study she should not have sexual intercourse with males without effective contraception (the rhythm method, withdrawal, and emergency contraception are not acceptable methods per the protocol).
  • Participant and participant's parent or guardian (participants aged 9-17 years only) provided written informed consent/assent.
  • Provided a primary and alternative telephone for follow-up purposes.
  • Extension Stage: participant was enrolled in the 9-19 years old group, received 3 doses of V501 in the Base Stage, and participant and participant's legally acceptable representative (if applicable) provided written informed consent/assent for the study extension.

Exclusion Criteria:

  • History of severe allergic reaction that required medical intervention.
  • Allergic to any vaccine component, including aluminum, yeast, or Benzonase® (nuclease).
  • Known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections.
  • Currently immunocompromised or was diagnosed as having congenital or acquired immunodeficiency, human immunodeficiency virus (HIV) infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease, or other autoimmune condition.
  • History of splenectomy.
  • Any condition which in the opinion of the investigator might interfere with the evaluation of the study objectives.
  • History of recent or ongoing alcohol or other drug abuse.
  • History of a positive test for HPV.
  • Any history of abnormal Pap test.
  • History of external genital wart, vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), vulvar cancer or vaginal cancer.
  • Undergone hysterectomy (either vaginal or total abdominal hysterectomy).
  • Receiving or has received in the year prior to Day 1 vaccination an excluded immunosuppressive therapy. A participant will be excluded if she is currently receiving steroid therapy, has recently received such therapy, or has received 2 or more courses of corticosteroids (orally or parenterally) lasting at least 1 week in duration in the year prior to Day 1 vaccination. Participants using inhaled, nasal or topical steroids are considered eligible for the study.
  • Received immune globulin product or blood-derived product within 6 months prior to Day 1 vaccination, or plans to receive any such product during the study.
  • Received a marketed HPV vaccine, or has participated in an HPV vaccine clinical trial and has received either active agent or placebo.
  • Received inactivated or recombinant vaccines within 14 days prior to Day 1 vaccination or receipt of live vaccines within 21 days prior to Day 1 vaccination.
  • Concurrently enrolled in a clinical study of investigational agents.
  • Had >4 lifetime sexual partners.
  • Unlikely to adhere to the study procedures, keep appointments, or is planning to permanently relocate from the area prior to the completion of the study or to leave for an extended period of time when study visits would need to be scheduled.
  • An immediate family member who is investigational site or sponsor staff directly involved with this study.
  • Extension Stage: reported overdose or received non-study HPV vaccine during the Base Stage.

Sites / Locations

  • Yangchun Center For Disease Prevention And Control ( Site 0003)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Chinese Girls Aged 9 to 19 Years

Chinese Young Women Aged 20 to 26 Years

Arm Description

Participants will receive V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6

Participants will receive V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6

Outcomes

Primary Outcome Measures

Geometric Mean Titers for Serum Anti-Human Papillomavirus (HPV) Types 6, 11, 16, and 18: Competitive Luminex Immunoassay (cLIA): Base Stage
Antibodies to HPV Types 6, 11, 16, and 18 were measured using a cLIA. Antibody titers were expressed as milli Merck Units/milliliter (mMU/mL).
Antibody Titers as Measured by cLIA: Extension Stage
Geometric mean titers to HPV Types 6, 11, 16, and 18 will be assessed. Antibodies will be measured using a Competitive Luminex Immunoassay (cLIA). This Outcome Measure applies only to participants aged 9 to 19 years.
Seropositivity Rates as Measured by cLIA: Extension Stage:
The percentage of participants who are seropositive to each of HPV Types 6, 11, 16, and 18 will be assessed. Antibodies will be measured using cLIA. This Outcome Measure applies only to participants aged 9 to 19 years.
Antibody Titers as Measured by Immunoglobulin G Luminex Immunoassay: Extension Stage:
Geometric mean titers to HPV Types 6, 11, 16, and 18 will be assessed. Antibodies will be measured using an Immunoglobulin G Luminex Immunoassay (IgG LIA). This Outcome Measure applies only to participants aged 9 to 19 years.
Seropositivity Rates as Measured by IgG LIA: Extension Stage:
The percentage of participants who are seropositive to each of HPV Types 6, 11, 16, and 18 will be assessed. Antibodies will be measured using IgG LIA. This Outcome Measure applies only to participants aged 9 to 19 years.

Secondary Outcome Measures

Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: cLIA: Base Stage
The percentage of participants who seroconverted to each of HPV Types 6, 11, 16, and 18 was assessed. Antibodies were measured using cLIA.
Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18: IgG LIA: Base Stage
Antibodies to HPV Types 6, 11, 16, and 18 were measured using an IgG LIA. Antibody titers were expressed as milli Merck Units/milliliter (mMU/mL).
Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: IgG LIA: Base Stage
The percentage of participants who seroconverted to each of HPV Types 6, 11, 16, and 18 was assessed. Antibodies were measured using IgG LIA.
Percentage of Participants With a Solicited Injection-site Adverse Event (AE): Base Stage
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited injection-site AEs included injection-site redness, swelling, induration, pain, and pruritus.
Percentage of Participants With a Solicited Systemic AE: Base Stage
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited systemic AEs included hypersensitivity, headache, fatigue, vomiting, nausea, diarrhea, myalgia, pyrexia, and cough.
Percentage of Participants Who Have a Serious Adverse Event (SAE): Base Stage
An SAE is an AE that results in death, is life threatening, requires hospitalization or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, according to medical or scientific judgment, may jeopardize the participant or requires medical or surgical intervention to prevent one of the other outcomes listed in the above definition.
Percentage of Participants With Any AE: Base Stage
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment
Maximum Axillary Temperature: Merck Sharp & Dohme (MSD) Criteria: Base Stage
In the global studies, fever is defined as an oral temperature of ≥37.8°C or 100.0°F, which is equivalent to axillary temperature of ≥37.2°C, while the definition of fever is axillary temperature of ≥37.1°C in Chinese criteria. To be compliant to Chinese criteria, axillary temperatures of ≥37.1°C was considered as a fever in this study. Body temperature readings assessed orally were converted to the axillary equivalent. The percentage of participants with a maximum axillary or converted axillary temperature was summarized by temperature range.
Serious Adverse Events: Extension Stage:
The percentage of participants with an SAE will be assessed. An SAE is an AE that results in death, is life threatening, requires hospitalization or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, according to medical or scientific judgment, may jeopardize the participant or requires medical or surgical intervention to prevent one of the other outcomes listed in the above definition. This Outcome Measure applies only to participants aged 9 to 19 years.

Full Information

First Posted
April 4, 2018
Last Updated
August 14, 2020
Sponsor
Merck Sharp & Dohme LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT03493542
Brief Title
A Study to Evaluate the Immunogenicity, Safety and Tolerability of Quadrivalent Human Papillomavirus Vaccine (V501) in Chinese Girls Aged 9-19 Years and Young Women Aged 20-26 Years (V501-213)
Official Title
A Phase 3 Open-Label Clinical Trial to Study the Immunogenicity, Safety and Tolerability of Recombinant Human Papillomavirus Quadrivalent (Types 6, 11, 16, 18) Vaccine (V501) in Chinese Girls Aged 9-19 Years and Young Women Aged 20-26 Years
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 31, 2018 (Actual)
Primary Completion Date
May 1, 2019 (Actual)
Study Completion Date
January 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is designed to evaluate the immunogenicity, safety, and tolerability of Gardasil® (quadrivalent human papillomavirus [qHPV] vaccine, V501) in Chinese girls aged 9-19 years and young women aged 20-26 years. The primary hypothesis of the study states that at 1 month postdose 3, a 3-dose regimen of V501 induces non-inferior geometric mean titers (GMTs) for serum anti-HPV 6, anti-HPV 11, anti-HPV 16, anti-HPV 18 in girls aged 9-19 years compared to young women aged 20-26 years.
Detailed Description
The study consists of a Base Stage wherein Chinese girls aged 9-19 years and young women aged 20-26 years receive a 3-dose regimen of V501 and are followed up to 1 month postdose 3 (Month 7). Participants aged 9-19 years who received 3 doses of V501 in the Base Stage will be eligible to participate in the Extension Stage and will be followed up to Month 60. No study vaccine will be administered during the Extension Stage.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prevention of HPV Types 16- and 18-related Cervical Cancer, Cervical Intraepithelial Neoplasia (CIN) 1/2/3, and Cervical Adenocarcinoma in Situ

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
766 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Chinese Girls Aged 9 to 19 Years
Arm Type
Experimental
Arm Description
Participants will receive V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6
Arm Title
Chinese Young Women Aged 20 to 26 Years
Arm Type
Active Comparator
Arm Description
Participants will receive V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6
Intervention Type
Biological
Intervention Name(s)
V501
Other Intervention Name(s)
(Gardasil®) human papillomavirus (types 6, 11, 16, 18) recombinant vaccine, qHPV
Intervention Description
0.5 mL intramuscular injection in the deltoid muscle at Day 1, Month 2, and Month 6
Primary Outcome Measure Information:
Title
Geometric Mean Titers for Serum Anti-Human Papillomavirus (HPV) Types 6, 11, 16, and 18: Competitive Luminex Immunoassay (cLIA): Base Stage
Description
Antibodies to HPV Types 6, 11, 16, and 18 were measured using a cLIA. Antibody titers were expressed as milli Merck Units/milliliter (mMU/mL).
Time Frame
Month 7 (1 month postdose 3)
Title
Antibody Titers as Measured by cLIA: Extension Stage
Description
Geometric mean titers to HPV Types 6, 11, 16, and 18 will be assessed. Antibodies will be measured using a Competitive Luminex Immunoassay (cLIA). This Outcome Measure applies only to participants aged 9 to 19 years.
Time Frame
Month 12, 24, 36, 48, and 60
Title
Seropositivity Rates as Measured by cLIA: Extension Stage:
Description
The percentage of participants who are seropositive to each of HPV Types 6, 11, 16, and 18 will be assessed. Antibodies will be measured using cLIA. This Outcome Measure applies only to participants aged 9 to 19 years.
Time Frame
Month 12, 24, 36, 48, and 60
Title
Antibody Titers as Measured by Immunoglobulin G Luminex Immunoassay: Extension Stage:
Description
Geometric mean titers to HPV Types 6, 11, 16, and 18 will be assessed. Antibodies will be measured using an Immunoglobulin G Luminex Immunoassay (IgG LIA). This Outcome Measure applies only to participants aged 9 to 19 years.
Time Frame
Month 12, 24, 36, 48, and 60
Title
Seropositivity Rates as Measured by IgG LIA: Extension Stage:
Description
The percentage of participants who are seropositive to each of HPV Types 6, 11, 16, and 18 will be assessed. Antibodies will be measured using IgG LIA. This Outcome Measure applies only to participants aged 9 to 19 years.
Time Frame
Month 12, 24, 36, 48, and 60
Secondary Outcome Measure Information:
Title
Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: cLIA: Base Stage
Description
The percentage of participants who seroconverted to each of HPV Types 6, 11, 16, and 18 was assessed. Antibodies were measured using cLIA.
Time Frame
Month 7 (1 month postdose 3)
Title
Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18: IgG LIA: Base Stage
Description
Antibodies to HPV Types 6, 11, 16, and 18 were measured using an IgG LIA. Antibody titers were expressed as milli Merck Units/milliliter (mMU/mL).
Time Frame
Month 7 (1 month postdose 3)
Title
Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: IgG LIA: Base Stage
Description
The percentage of participants who seroconverted to each of HPV Types 6, 11, 16, and 18 was assessed. Antibodies were measured using IgG LIA.
Time Frame
Month 7 (1 month postdose 3)
Title
Percentage of Participants With a Solicited Injection-site Adverse Event (AE): Base Stage
Description
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited injection-site AEs included injection-site redness, swelling, induration, pain, and pruritus.
Time Frame
Up to 15 days after any vaccination
Title
Percentage of Participants With a Solicited Systemic AE: Base Stage
Description
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited systemic AEs included hypersensitivity, headache, fatigue, vomiting, nausea, diarrhea, myalgia, pyrexia, and cough.
Time Frame
Up to 15 days after any vaccination
Title
Percentage of Participants Who Have a Serious Adverse Event (SAE): Base Stage
Description
An SAE is an AE that results in death, is life threatening, requires hospitalization or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, according to medical or scientific judgment, may jeopardize the participant or requires medical or surgical intervention to prevent one of the other outcomes listed in the above definition.
Time Frame
Up to Month 7 (1 month postdose 3)
Title
Percentage of Participants With Any AE: Base Stage
Description
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment
Time Frame
Up to 31 days after any vaccination
Title
Maximum Axillary Temperature: Merck Sharp & Dohme (MSD) Criteria: Base Stage
Description
In the global studies, fever is defined as an oral temperature of ≥37.8°C or 100.0°F, which is equivalent to axillary temperature of ≥37.2°C, while the definition of fever is axillary temperature of ≥37.1°C in Chinese criteria. To be compliant to Chinese criteria, axillary temperatures of ≥37.1°C was considered as a fever in this study. Body temperature readings assessed orally were converted to the axillary equivalent. The percentage of participants with a maximum axillary or converted axillary temperature was summarized by temperature range.
Time Frame
Up to 5 days after any vaccination
Title
Serious Adverse Events: Extension Stage:
Description
The percentage of participants with an SAE will be assessed. An SAE is an AE that results in death, is life threatening, requires hospitalization or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, according to medical or scientific judgment, may jeopardize the participant or requires medical or surgical intervention to prevent one of the other outcomes listed in the above definition. This Outcome Measure applies only to participants aged 9 to 19 years.
Time Frame
Up to Month 60

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
9 Years
Maximum Age & Unit of Time
26 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Not pregnant and 1) not a woman of childbearing potential (WOCBP), or 2) a WOCBP who has not had sex with males or has had sex with males and used effective contraception since the first day of participant's last menstrual period through Day 1 and understands and agrees that during the study she should not have sexual intercourse with males without effective contraception (the rhythm method, withdrawal, and emergency contraception are not acceptable methods per the protocol). Participant and participant's parent or guardian (participants aged 9-17 years only) provided written informed consent/assent. Provided a primary and alternative telephone for follow-up purposes. Extension Stage: participant was enrolled in the 9-19 years old group, received 3 doses of V501 in the Base Stage, and participant and participant's legally acceptable representative (if applicable) provided written informed consent/assent for the study extension. Exclusion Criteria: History of severe allergic reaction that required medical intervention. Allergic to any vaccine component, including aluminum, yeast, or Benzonase® (nuclease). Known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections. Currently immunocompromised or was diagnosed as having congenital or acquired immunodeficiency, human immunodeficiency virus (HIV) infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease, or other autoimmune condition. History of splenectomy. Any condition which in the opinion of the investigator might interfere with the evaluation of the study objectives. History of recent or ongoing alcohol or other drug abuse. History of a positive test for HPV. Any history of abnormal Pap test. History of external genital wart, vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), vulvar cancer or vaginal cancer. Undergone hysterectomy (either vaginal or total abdominal hysterectomy). Receiving or has received in the year prior to Day 1 vaccination an excluded immunosuppressive therapy. A participant will be excluded if she is currently receiving steroid therapy, has recently received such therapy, or has received 2 or more courses of corticosteroids (orally or parenterally) lasting at least 1 week in duration in the year prior to Day 1 vaccination. Participants using inhaled, nasal or topical steroids are considered eligible for the study. Received immune globulin product or blood-derived product within 6 months prior to Day 1 vaccination, or plans to receive any such product during the study. Received a marketed HPV vaccine, or has participated in an HPV vaccine clinical trial and has received either active agent or placebo. Received inactivated or recombinant vaccines within 14 days prior to Day 1 vaccination or receipt of live vaccines within 21 days prior to Day 1 vaccination. Concurrently enrolled in a clinical study of investigational agents. Had >4 lifetime sexual partners. Unlikely to adhere to the study procedures, keep appointments, or is planning to permanently relocate from the area prior to the completion of the study or to leave for an extended period of time when study visits would need to be scheduled. An immediate family member who is investigational site or sponsor staff directly involved with this study. Extension Stage: reported overdose or received non-study HPV vaccine during the Base Stage.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Yangchun Center For Disease Prevention And Control ( Site 0003)
City
Yangchun
State/Province
Guangdong
ZIP/Postal Code
529600
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
33239228
Citation
Huang Z, He J, Su J, Ou Z, Liu G, Fu R, Shou Q, Zheng M, Group T, Luxembourg A, Liao X, Zhang J. Immunogenicity and safety of the quadrivalent human papillomavirus vaccine in Chinese females aged 9 to 26 years: A phase 3, open-label, immunobridging study. Vaccine. 2021 Jan 22;39(4):760-766. doi: 10.1016/j.vaccine.2020.11.008. Epub 2020 Nov 22.
Results Reference
derived

Learn more about this trial

A Study to Evaluate the Immunogenicity, Safety and Tolerability of Quadrivalent Human Papillomavirus Vaccine (V501) in Chinese Girls Aged 9-19 Years and Young Women Aged 20-26 Years (V501-213)

We'll reach out to this number within 24 hrs