Clinical trial NCT03493542: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prevention of HPV Types 16- and 18-related Cervical Cancer, Cervical Intraepithelial Neoplasia (CIN) 1/2/3, and Cervical Adenocarcinoma in Situ
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-04-10
Enrollment: 766
Sex: FEMALE
Minimum age (years): 9
Maximum age (years): 26
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Base Stage: Geometric Mean Titers for Serum Anti-Human Papillomavirus (HPV) Types 6, 11, 16, and 18: Competitive Luminex Immunoassay (cLIA)
timeFrame: Month 7 (1 month postdose 3)
measure: Extension Stage: GMTs for Serum Anti-Human Papillomavirus (HPV) Types 6, 11, 16, and 18 at Month 12 Assessed by cLIA
timeFrame: Month 12 post-vaccination 1
measure: Extension Stage: GMTs for Serum Anti-Human Papillomavirus (HPV) Types 6, 11, 16, and 18 at Month 24 Assessed by cLIA
timeFrame: Month 24 post-vaccination 1
measure: Extension Stage: GMTs for Serum Anti-Human Papillomavirus (HPV) Types 6, 11, 16, and 18 at Month 36 Assessed by cLIA
timeFrame: Month 36 post-vaccination 1
measure: Extension Stage: GMTs for Serum Anti-Human Papillomavirus (HPV) Types 6, 11, 16, and 18 at Month 48 Assessed by cLIA
timeFrame: Month 48 post-vaccination 1
measure: Extension Stage: GMTs for Serum Anti-Human Papillomavirus (HPV) Types 6, 11, 16, and 18 at Month 60 Assessed by cLIA
timeFrame: Month 60 post-vaccination 1
measure: Extension Stage: Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 12 Assessed by cLIA
timeFrame: Month 12 post-vaccination 1
measure: Extension Stage: Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 24 Assessed by cLIA
timeFrame: Month 24 post-vaccination 1
measure: Extension Stage: Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 36 Assessed by cLIA
timeFrame: Month 36 post-vaccination 1
measure: Extension Stage: Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 48 Assessed by cLIA
timeFrame: Month 48 post-vaccination 1
measure: Extension Stage: Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 60 Assessed by cLIA
timeFrame: Month 60 post-vaccination 1
measure: Extension Stage: GMTs for Serum Anti-HPV Types 6, 11, 16, and 18 at Month 12 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA)
timeFrame: Month 12 post-vaccination 1
measure: Extension Stage: GMTs for Serum Anti-HPV Types 6, 11, 16, and 18 at Month 24 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA)
timeFrame: Month 24 post-vaccination 1
measure: Extension Stage: GMTs for Serum Anti-HPV Types 6, 11, 16, and 18 at Month 36 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA)
timeFrame: Month 36 post-vaccination 1
measure: Extension Stage: GMTs for Serum Anti-HPV Types 6, 11, 16, and 18 at Month 48 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA)
timeFrame: Month 48 post-vaccination 1
measure: Extension Stage: GMTs for Serum Anti-HPV Types 6, 11, 16, and 18 at Month 60 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA)
timeFrame: Month 60 post-vaccination 1
measure: Extension Stage: Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 12 Assessed by IgG LIA
timeFrame: Month 12 post-vaccination 1
measure: Extension Stage: Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 24 Assessed by IgG LIA
timeFrame: Month 24 post-vaccination 1
measure: Extension Stage: Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 36 Assessed by IgG LIA
timeFrame: Month 36 post-vaccination 1
measure: Extension Stage: Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 48 Assessed by IgG LIA
timeFrame: Month 48 post-vaccination 1
measure: Extension Stage: Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 60 Assessed by IgG LIA
timeFrame: Month 60 post-vaccination 1
Secondary outcomes:
measure: Base Stage: Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: cLIA
timeFrame: Month 7 (1 month postdose 3)
measure: Base Stage: Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18: IgG LIA
timeFrame: Month 7 (1 month postdose 3)
measure: Base Stage: Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: IgG LIA
timeFrame: Month 7 (1 month postdose 3)
measure: Base Stage: Percentage of Participants Who Experienced a Solicited Injection-site Adverse Event (AE)
timeFrame: Up to 15 days after any vaccination
measure: Base Stage: Percentage of Participants Participants Who Experienced a Solicited Systemic AE
timeFrame: Up to 15 days after any vaccination
measure: Base Stage: Percentage of Participants Who Experienced a Serious Adverse Event (SAE)
timeFrame: Up to Month 7 (1 month postdose 3)
measure: Base Stage: Percentage of Participants Who Experienced an AE
timeFrame: Up to 31 days after any vaccination
measure: Base Stage: Maximum Axillary Temperature: Merck Sharp & Dohme (MSD) Criteria
timeFrame: Up to 5 days after any vaccination
measure: Extension Stage: Percentage of Participants Who Experienced an SAE
timeFrame: Month 7 up to Month 60
Other outcomes:
Locations:
city: Yangchun
country: China
facility: Yangchun Center For Disease Prevention And Control ( Site 0003)
state: Guangdong
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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.