Clinical Trials List
Protocol NumberV503-069
NCT Number(ClinicalTrials.gov Identfier)NCT04708041
2021-02-01 - 2030-03-31
Phase III
Not yet recruiting3
ICD-10B97.7
Papillomavirus as the cause of diseases classified elsewhere
ICD-9079.4
Human papilloma virus infections in conditions classified elsewhere and of unspecified site
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
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Sponsor
Merck Sharp & Dohme Corp.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Yhu-Chering Huang Division of Pediatrics
- 黃冠穎 Division of Pediatrics
- 謝育嘉 Division of Pediatrics
- Chi-Long Chen Division of Pediatrics
- 陳苡靜 Division of Pediatrics
- 郭貞孍 Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- FANG-LIANG HUANG Division of Pediatrics
- 許雅淇 Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 蔡幸真 Division of Pediatrics
- 陳立倫 Division of Pediatrics
- 楊德亮 Division of Pediatrics
- 吳季憲 Division of Pediatrics
- 何昇原 Division of Pediatrics
- Luan-Yin Chang Division of Pediatrics
- 戴君芙 Division of Pediatrics
- 劉裕誠 Division of Pediatrics
- 胡雅莉 Division of Pediatrics
- 白孟丘 Division of Pediatrics
- 馬瑄吟 Division of Pediatrics
- 林筱琪 Division of Pediatrics
- 丁詠恬 Division of Pediatrics
- 黃筱倫 Division of Pediatrics
- Chun-yi Lu Division of Pediatrics
- 邢子芸 Division of Pediatrics
- 賴貞吟 Division of Pediatrics
- 黃崧銘 Division of Pediatrics
- 周昱廷 Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Condition/Disease
Human Papillomavirus(HPV) Infections
Objectives
Primary Objective #1: In a population who are seronegative to the relevant HPV type at Day 1, to demonstrate that administration of a 2-dose regimen of 9vHPV vaccine in boys and girls 9 to 14 years of age induces noninferior cLIA GMTs of antibodies to each of the 9vHPV vaccine types compared with young women 16 to 26 years of age receiving a 3-dose regimen of the same vaccine at Day 1, Month 2, and Month 6.
Primary Objective #2:In 10-to 15-year old boys and girls who received a single dose of 9vHPV vaccine at least 1 year prior to enrollment, to characterize the immune response to a second dose of 9vHPV vaccine (as measured by cLIA GMTs of antibodies to each of the 9vHPV vaccine types) at 4 weeks post dose 2 taking into account the time interval between administration of doses 1 and 2.
Primary Objective #3:To evaluate the safety of administering the 9vHPV vaccine based on the dosing regimens investigated in this study.
Test Drug
Gardasil 9
Active Ingredient
Human Papillomavirus 9-valent Vaccine, Recombinant
Dosage Form
IVT
Dosage
NA
Endpoints
Primary Outcome Measures :
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 [ Time Frame: 4 weeks post last vaccination (Up to ~Month 61) ]
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).
Percentage of Participants With at Least 1 Solicited Injection-site Adverse Event [ Time Frame: Up to 5 days post vaccination ]
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.
Percentage of Participants With at Least 1 Systemic Adverse Event [ Time Frame: Up to 15 days post vaccination ]
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.
Percentage of Participants With at Least 1 Serious Vaccine-Related Adverse Event [ Time Frame: Entire study period (Up to ~Month 96) ]
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.
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 [ Time Frame: 4 weeks post last vaccination (Up to ~Month 61) ]
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).
Percentage of Participants With at Least 1 Solicited Injection-site Adverse Event [ Time Frame: Up to 5 days post vaccination ]
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.
Percentage of Participants With at Least 1 Systemic Adverse Event [ Time Frame: Up to 15 days post vaccination ]
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.
Percentage of Participants With at Least 1 Serious Vaccine-Related Adverse Event [ Time Frame: Entire study period (Up to ~Month 96) ]
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.
Inclution Criteria
1. Is healthyindividual who meets all inclusioncriteriaand none of the exclusiondefined in this section.
2. Is male orfemale, from 10 years to 15 years of age inclusive, who received 1 dose of 9vHPV vaccine at least 1 year prior to enrollmentand did not receive Dose 2 of any HPV vaccine (Cohort 0).
3. Is male or female, from9 years to 14 years of age inclusive, on the day of enrollment (Cohorts 1to 4).
4. Is female, from 16 yearsto 26 years inclusive, on the day of enrollment(Cohort 5).
5.(Participants 9 to 15years of age only)Has not yet had coitarche and does not plan on becoming sexually active during the vaccination period.
6.(Female participants 16 to 26 years of age only)Has never had Pap testing (cervical or anal) or has had only normal Pap test results.
7. (Female participants16 to 26 years of age only) Has a lifetime history of 0 to 4 male and/or female sexual partners at the time of enrollment. Male or female partner is defined as someone with whom the participant has had penile penetrative sexual intercourse or someone who has contacted, either by penetrative (with fingers or other objects) or non-penetrative means, the participant's genitalia during sexual activity.
8. (Female participants 16 to 26 years of age only, defined as WOCBP in Appendix5) Has not had sex with males or has had sex with males and used effective contraception with no failures (Appendix5) since the first day of the participant’s last menstrual period through Day 1. The participant understands and agrees that during the interventionperiod, sheshould not have sexual intercourse with males without effective contraception, and that the use of the rhythm method, withdrawal, and emergencycontraception are not acceptable methods per the protocol.Effective contraception is defined as a marketed, approved contraceptive product that the participant has used per the manufacturer’s instructions with every act of sexual intercourse (Appendix5).
9. Participant or participant’s legally acceptable representative understands the studyprocedures, alternate treatments available, and risks involved with the study and voluntarily agrees to participate by providing documentedinformed consent. As appropriate based on local guidelines, the participant will also provide documentedinformed assent for the study. The participant or the participant’s legally acceptable representative may also provide assent/consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research.
10. Agrees to provide study personnel with a primary telephone number as well as an alternate form of contact, if available, for follow-up purposes.
11. Participant or participant’s legally acceptable representative can read, understand, and complete the eVRC.
2. Is male orfemale, from 10 years to 15 years of age inclusive, who received 1 dose of 9vHPV vaccine at least 1 year prior to enrollmentand did not receive Dose 2 of any HPV vaccine (Cohort 0).
3. Is male or female, from9 years to 14 years of age inclusive, on the day of enrollment (Cohorts 1to 4).
4. Is female, from 16 yearsto 26 years inclusive, on the day of enrollment(Cohort 5).
5.(Participants 9 to 15years of age only)Has not yet had coitarche and does not plan on becoming sexually active during the vaccination period.
6.(Female participants 16 to 26 years of age only)Has never had Pap testing (cervical or anal) or has had only normal Pap test results.
7. (Female participants16 to 26 years of age only) Has a lifetime history of 0 to 4 male and/or female sexual partners at the time of enrollment. Male or female partner is defined as someone with whom the participant has had penile penetrative sexual intercourse or someone who has contacted, either by penetrative (with fingers or other objects) or non-penetrative means, the participant's genitalia during sexual activity.
8. (Female participants 16 to 26 years of age only, defined as WOCBP in Appendix5) Has not had sex with males or has had sex with males and used effective contraception with no failures (Appendix5) since the first day of the participant’s last menstrual period through Day 1. The participant understands and agrees that during the interventionperiod, sheshould not have sexual intercourse with males without effective contraception, and that the use of the rhythm method, withdrawal, and emergencycontraception are not acceptable methods per the protocol.Effective contraception is defined as a marketed, approved contraceptive product that the participant has used per the manufacturer’s instructions with every act of sexual intercourse (Appendix5).
9. Participant or participant’s legally acceptable representative understands the studyprocedures, alternate treatments available, and risks involved with the study and voluntarily agrees to participate by providing documentedinformed consent. As appropriate based on local guidelines, the participant will also provide documentedinformed assent for the study. The participant or the participant’s legally acceptable representative may also provide assent/consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research.
10. Agrees to provide study personnel with a primary telephone number as well as an alternate form of contact, if available, for follow-up purposes.
11. Participant or participant’s legally acceptable representative can read, understand, and complete the eVRC.
Exclusion Criteria
1. *Has a fever (defined as oral temperature ≥100.0°F or ≥37.8°C) within the 24-hour period prior to the Day 1 visit.
2. Has a history of severe allergic reaction (eg, swelling of the mouth and throat, difficultybreathing, hypotension, or shock) that required medical intervention.
3. Is allergicto any vaccine component, including aluminum, yeast, or BENZONASETM(nuclease, Nycomed [used to remove residual nucleic acids from this and other vaccines]). For this exclusion criterion, an allergy to vaccine components is defined as an allergic reactionthat met the criteria for severe AEs or SAEs defined in Appendix 3.
4. Has known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections.
5. Is currently immunocompromised or has been diagnosed as having congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune condition.
6. Has a history of splenectomy.
7. Is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence at the discretion of the investigator. Alcohol abusers are defined as those who drink despite recurrent social, interpersonal, and/or legal problems because of alcohol use.
8. Has a history of a positive test for HPV.
9.(Female participants 16 to 26 years of age only)Has a history of an abnormal cervical biopsy result (showing cervical intraepithelial neoplasia or worse).
10.(Female participants 16 to 26 years of age only) Has a history of HPV-related external genital lesions (eg, condyloma acuminata, or vulvar intraepithelial neoplasia) or external genital cancer, HPV-related vaginal lesions (eg, condyloma acuminata, or vaginal intraepithelial neoplasia) or vaginal cancer, or HPV-related anal lesions (eg, condyloma acuminata, or anal intraepithelial neoplasia) or anal cancer.
11.(Female participants only)Is pregnant as determined by a serum pregnancy test or urine pregnancy test that is sensitive to 25 mIU/mL β-hCG.
12.(Female participants only)Is expecting to donate eggs during the intervention periodofthe study.
13. Has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study, or interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate by judgmentof investigator.
The history of medical conditions will be based on the self-report or medical recordprovided by the participantor the participant’s legally acceptable representative.
14. Has received within 12 months prior to enrollment, is receiving, or plans to receive during the study, the following immunosuppressive therapies: radiation therapy, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporin, leflunomide (AravaTM), TNF-α antagonists, monoclonal antibody therapies (includingrituximab [Rituxan™]), IVIG, antilymphocyte sera, or other therapy known to interfere with the immune response. Regarding systemic corticosteroids, a participant will be excluded if he/she is currently receiving steroid therapy, has recently (defined as within 2 weeks of Day 1 vaccination) received such therapy, or has received 2 or more courses of corticosteroids 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.
15. Has received within the 3 months prior to the Day 1 vaccination, is receiving, or plans to receive during the study, any immune globulin product (including RhoGAM™ [Ortho-Clinical Diagnostics]) or blood-derived product other than IVIG
16. *Has 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 (Note: If there is local requirement for the longer period between receipt of live vaccines and studyvaccine, then it should follow local regulatory requirement.)
17. Is concurrently enrolled in other clinical studies of investigational agents.
18. Has received more than 1 dose of an HPV vaccine (Cohort 0).
19. Has previously received a marketedor investigationalHPV vaccine(Cohorts 1 to 5).
20. Has participated in a clinical study for any HPV vaccine (receiving either active agent or placebo)
21. Is unlikely to adhere to the study procedures, keep appointments, or is planning topermanently relocate from the area prior to the completion of the study or to leave foran extended period when study visits would need to be scheduled.
22. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.
* For items denoted with an asterisk, if the exclusioncriterion is met, then the Day 1 visit may be rescheduled for a time when the criterion is not met
2. Has a history of severe allergic reaction (eg, swelling of the mouth and throat, difficultybreathing, hypotension, or shock) that required medical intervention.
3. Is allergicto any vaccine component, including aluminum, yeast, or BENZONASETM(nuclease, Nycomed [used to remove residual nucleic acids from this and other vaccines]). For this exclusion criterion, an allergy to vaccine components is defined as an allergic reactionthat met the criteria for severe AEs or SAEs defined in Appendix 3.
4. Has known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections.
5. Is currently immunocompromised or has been diagnosed as having congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune condition.
6. Has a history of splenectomy.
7. Is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence at the discretion of the investigator. Alcohol abusers are defined as those who drink despite recurrent social, interpersonal, and/or legal problems because of alcohol use.
8. Has a history of a positive test for HPV.
9.(Female participants 16 to 26 years of age only)Has a history of an abnormal cervical biopsy result (showing cervical intraepithelial neoplasia or worse).
10.(Female participants 16 to 26 years of age only) Has a history of HPV-related external genital lesions (eg, condyloma acuminata, or vulvar intraepithelial neoplasia) or external genital cancer, HPV-related vaginal lesions (eg, condyloma acuminata, or vaginal intraepithelial neoplasia) or vaginal cancer, or HPV-related anal lesions (eg, condyloma acuminata, or anal intraepithelial neoplasia) or anal cancer.
11.(Female participants only)Is pregnant as determined by a serum pregnancy test or urine pregnancy test that is sensitive to 25 mIU/mL β-hCG.
12.(Female participants only)Is expecting to donate eggs during the intervention periodofthe study.
13. Has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study, or interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate by judgmentof investigator.
The history of medical conditions will be based on the self-report or medical recordprovided by the participantor the participant’s legally acceptable representative.
14. Has received within 12 months prior to enrollment, is receiving, or plans to receive during the study, the following immunosuppressive therapies: radiation therapy, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporin, leflunomide (AravaTM), TNF-α antagonists, monoclonal antibody therapies (includingrituximab [Rituxan™]), IVIG, antilymphocyte sera, or other therapy known to interfere with the immune response. Regarding systemic corticosteroids, a participant will be excluded if he/she is currently receiving steroid therapy, has recently (defined as within 2 weeks of Day 1 vaccination) received such therapy, or has received 2 or more courses of corticosteroids 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.
15. Has received within the 3 months prior to the Day 1 vaccination, is receiving, or plans to receive during the study, any immune globulin product (including RhoGAM™ [Ortho-Clinical Diagnostics]) or blood-derived product other than IVIG
16. *Has 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 (Note: If there is local requirement for the longer period between receipt of live vaccines and studyvaccine, then it should follow local regulatory requirement.)
17. Is concurrently enrolled in other clinical studies of investigational agents.
18. Has received more than 1 dose of an HPV vaccine (Cohort 0).
19. Has previously received a marketedor investigationalHPV vaccine(Cohorts 1 to 5).
20. Has participated in a clinical study for any HPV vaccine (receiving either active agent or placebo)
21. Is unlikely to adhere to the study procedures, keep appointments, or is planning topermanently relocate from the area prior to the completion of the study or to leave foran extended period when study visits would need to be scheduled.
22. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.
* For items denoted with an asterisk, if the exclusioncriterion is met, then the Day 1 visit may be rescheduled for a time when the criterion is not met
The Estimated Number of Participants
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Taiwan
90 participants
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Global
700 participants
