A Study to Evaluate the Efficacy, Safety, and Immunogenicity of SCT1000 in Healthy Women Aged 18-45 Years

Study Overview
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Brief Summary
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A total of 18000 healthy women aged 18-45 years old were divided into three age groups: 18-26 years old, 27-35 years old, and 36-45 years old. The experimental group and the placebo group were randomly assigned in a ratio of 1:1. All subjects enrolled in the upper arm deltoid muscle were injected with 3 doses of test vaccine or placebo according to the 0, 2, and 6 months immunization program.

Detailed Description
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Introduction: SCT1000 is a recombinant 14-valent human papillomavirus vaccine (insect cell) that covers all 12 WHO-recognized high-risk oncogenic HPV subtypes Indications are for the prevention of cervical, vulvar, vaginal, and anal cancers, and genital warts caused by HPV6, HPV11 and HPV11 in females 9-45 years of age, as well as intraepithelial neoplasia and AIS. Intraepithelial neoplasia and AIS and genital warts due to HPV6 and HPV11. Aim:To evaluate the protective efficacy of 3 doses of HPV vaccine (SCT1000) for the prevention of HPV type 6,11,16,18,31,33,35,39,45,51,52,56,58,59-associated lesions in healthy females aged 18-45 years compared with placebo. Design: A Multicenter, Randomized, Double-blind, Placebo-controlled phase III Clinical trial Subject Information: a total of 18000 healthy women aged 18-45 years selected by inclusion and exclusion criteria. Cluster situation: a ratio of 1:1 between the experimental group and the placebo group. End point index: relative index with efficacy, safety, and immunogenicity of SCT1000

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Clinical Trial Evaluating the Efficacy, Safety, and Immunogenicity of a 14- Valent Recombinant Human Papillomavirus Vaccine (SCT1000) in Healthy Women Aged 18-45 Years

Conditions
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HPV InfectioN, HPV-Related Carcinoma

Intervention / Treatment
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* Biological: Recombinant 14-Valent Human Papillomavirus Vaccine（Insect Cell）
* Biological: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Females who are at least 18 years old and less than 46 years old (i.e., 18 to 45 years old). 2. Subjects sign a written informed consent form (ICF) to participate in the trial voluntarily, and are able to fully understand the trial procedures, the risks of participating in the trial, and the alternative interventions available to them if they do not participate in the trial. 3. Be able to read, understand and complete the diary/contact card. 4. Be in good health as judged by the history interview and physical examination. 5. Have a history of sexual behavior prior to enrollment. 6.*Avoid sexual intercourse (including same-sex or opposite-sex anal, vaginal, or genital/genital contact) and avoid vaginal douching, vaginal cleansing, or the use of vaginal medications or preparations for 48 hours prior to any visit that includes sample collection. 7. Subjects who are not breastfeeding at the time of enrollment and who have used effective contraception from the time of their last menstrual period until enrollment in the study, and who understand and agree to use effective contraception from the first day of enrollment until 1 month after the last vaccination. 8.* Those with axillary body temperature <37.3°C on the day of enrollment. 9. Note: Subjects who do not meet the *enrollment criteria are allowed to be screened again, but the enrollment criteria still need to be confirmed again at the time of enrollment. Exclusion Criteria: 1. *Positive urine pregnancy test or pregnancy (including ectopic pregnancy) that has ended less than 6 weeks ago. 2. Prior vaccination with a marketed HPV vaccine or already enrolled in a clinical trial of another HPV vaccine or have plans to receive a non-study HPV vaccine during the study period. 3. Have a prior history of cervical cancer screening abnormalities or lesions [including HPV DNA positivity, squamous intraepithelial lesions (SIL) or atypical squamous cells of undetermined significance (ASC-US), atypical squamous epithelial cells-without the exception of high grade squamous intraepithelial lesions (ASC-H), atypical glandular cells (AGC), or have cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ (AIS) or cervical cancer]. ) or cervical cancer, etc.]. 4. Previous or current anal or genital disease (e.g. vulvar intraepithelial neoplasia, vaginal intraepithelial neoplasia, genital warts, vulvar, vaginal, and anal cancers) 5. Previous total hysterectomy or pelvic radiation therapy or severe developmental abnormalities of the cervix/vagina. 6. History of drug or alcohol abuse or dependence in the last year. 7. Have hypertension or diabetes mellitus that cannot be controlled and stabilized with pharmacological interventions. 8. Subjects with a history of severe allergic reactions to any vaccine or medication requiring medical intervention (e.g., anaphylaxis, anaphylactic laryngeal edema, anaphylactic purpura, thrombocytopenic purpura, localized anaphylactic necrotic reaction [Arthus reaction], etc.). 9. Currently immunocompromised or diagnosed with congenital or acquired immunodeficiency, HIV infection, lymphoma, tuberculosis, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis (JRA), inflammatory bowel disease, or other autoimmune disease. 10. Previous splenectomy or impaired splenic function. 11. Currently receiving or have received the following immunosuppressive therapies in the last year: radiation therapy, cyclophosphamide, imidazathioprine, methotrexate, as well as chemotherapy, cyclosporine, leflunomide, tumor necrosis factor-alpha antagonists, monoclonal antibody therapies, intravenous gammaglobulin, anti-lymphocytic serums, or other therapies that are known to interfere with immunity 12. Current treatment with systemic corticosteroids or 2 or more courses of high-dose glucocorticoids lasting one week in the year prior to enrollment. The use of nasal inhaled glucocorticoids or topical short-term topical application on the skin may not be excluded. 13. Receipt of any immunoglobulin product or blood product within 3 months prior to vaccination, or planning to receive such similar products during the study period from Day 1 to Month 7. 14. * Inactivated/recombinant/nucleic acid vaccine, etc. (non-attenuated) within 14 days prior to vaccination or live attenuated vaccine within 28 days prior to vaccination. 15. Contraindication to intramuscular injection such as thrombocytopenia or other coagulation disorders. 16. *Blood donation within 1 week prior to vaccination or planning to donate blood between Day 1 and Month 7 of study participation. 17. Participation in other experimental clinical studies or studies with unregistered products (drugs or vaccines) or collection of cervical specimens within 3 months prior to vaccination. 18. Inability to follow trial procedures or planned relocation during the study. 19. *Fever (axillary temperature ≥37.3°C) within 3 days prior to vaccination or any acute illness requiring systemic antibiotic or antiviral therapy within the past 5 days. 20. *Clinical signs/symptoms suggestive of acute reproductive tract infection (e.g. acute vulvovaginitis/vaginitis/cervicitis [including purulent cervicitis], etc.) during gynecological examination. 21. * Being in the menstrual period (sampling should be done 2 days after the end of menstruation). 22. Have an active neurological/psychiatric/psychological disorder that prevents compliance with the study requirements. 23. Have other abnormalities, conditions that may confound the results of the study, or conditions that are not in the best interest of the subject and may be excluded as determined by the investigator. 24. Note: Subjects who meet *exclusion criteria are allowed to be re-screened, but enrollment will still require re-confirmation of inclusion criteria.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Recombinant 14-Valent Human Papillomavirus Vaccine (Types 6,11,16,18,31,33,35,39, 45,51,52,56,58,59) （Insect Cell）
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experiment group<br>According to the 0, 2, and 6 months immunization program, intramuscular injection of the upper arm deltoid muscle, 3 doses of the experiment vaccine | Biological: Recombinant 14-Valent Human Papillomavirus Vaccine（Insect Cell）<br>* According to the 0, 2, and 6 months immunization program, intramuscular injection of the upper arm deltoid muscle, 3 doses of the experiment vaccine<br>|
| Placebo Comparator: placebo<br>According to the 0, 2, and 6 months immunization program, intramuscular injection of the upper arm deltoid muscle, 3 doses of the placebo | Biological: placebo<br>* According to the 0, 2, and 6 months immunization program, intramuscular injection of the upper arm deltoid muscle, 3 doses of the placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined Incidence of HPV Type 16/18-related CIN2/3, AIS, Invasive cervical cancer, VIN2/3, VaIN2/3, AIN1/2/3, vulvar, vaginal and anal cancer | The endpoint is defined to have occurred: (a) a HPV Pathology Panel consensus diagnosis from the results of cervical biopsy: Cervical Intraepithelial Neoplasia (CIN, including grade 2 or 3), Adenocarcinoma in Situ (AIS), Invasive cervical cancer, Vulvar Intraepithelial Neoplasia (VIN, including grade 2 or 3), Vaginal Intraepithelial Neoplasia (VaIN, including grade 2 or 3), Anal intraepithelial neoplasia (AIN, including grade 1, 2, or 3), vulvar, vaginal and anal cancer; AND (b) detection of at least 1 of Human Papillomavirus (HPV) types 16/18 by Polymerase Chain Reaction (PCR) assay for virus subtype. | 1 month after 3 doses of vaccine | 
| Combined Incidence of HPV Type 31/33/45/52/58-related CIN2/3, AIS, Invasive cervical cancer, VIN2/3, VaIN2/3, AIN1/2/3, vulvar, vaginal and anal cancer | The endpoint is defined to have occurred: (a) a HPV Pathology Panel consensus diagnosis from the results of cervical biopsy: Cervical Intraepithelial Neoplasia (CIN, including grade 2 or 3), Adenocarcinoma in Situ (AIS), Invasive cervical cancer, Vulvar Intraepithelial Neoplasia (VIN, including grade 2 or 3), Vaginal Intraepithelial Neoplasia (VaIN, including grade 2 or 3), Anal intraepithelial neoplasia (AIN, including grade 1, 2, or 3), vulvar, vaginal and anal cancer; AND (b) detection of at least 1 of Human Papillomavirus (HPV) types 31/33/45/52/58 by Polymerase Chain Reaction (PCR) assay for virus subtype. | 1 month after 3 doses of vaccine | 
| Combined Incidence of HPV Type 35/39/51/56/59-related CIN2/3, AIS, Invasive cervical cancer, VIN2/3, VaIN2/3, AIN1/2/3, vulvar, vaginal and anal cancer | The endpoint is defined to have occurred: (a) a HPV Pathology Panel consensus diagnosis from the results of cervical biopsy: Cervical Intraepithelial Neoplasia (CIN, including grade 2 or 3), Adenocarcinoma in Situ (AIS), Invasive cervical cancer, Vulvar Intraepithelial Neoplasia (VIN, including grade 2 or 3), Vaginal Intraepithelial Neoplasia (VaIN, including grade 2 or 3), Anal intraepithelial neoplasia (AIN, including grade 1, 2, or 3), vulvar, vaginal and anal cancer; AND (b) detection of at least 1 of Human Papillomavirus (HPV) types 35/39/51/56/59 by Polymerase Chain Reaction (PCR) assay for virus subtype. | 1 month after 3 doses of vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of 6-month Persistent Infection associated with HPV types 16/18 | The endpoint of a 6-month Persistent Infection was defined to a subject was positive for the same HPV type by the HPV PCR assay to at least 1 common gene in 2 or more consecutive cervicovaginal/external genital swab, biopsy, or definitive therapy samples obtained for over a period of at least 6 months. | 1 month after 3 doses of vaccine | 
| Incidence of 12-month Persistent Infection associated with HPV types 16/18 | The endpoint of a 12-month Persistent Infection was defined to a subject was positive for the same HPV type by the HPV PCR assay to at least 1 common gene in 3 or more consecutive cervicovaginal/external genital swab, biopsy, or definitive therapy samples obtained for over a period of at least 12 months. | 1 month after 3 doses of vaccine | 
| Incidence of 6-month Persistent Infection associated with HPV types 31/33/45/52/58 | The endpoint of a 6-month Persistent Infection was defined to a subject was positive for the same HPV type by the HPV PCR assay to at least 1 common gene in 2 or more consecutive cervicovaginal/external genital swab, biopsy, or definitive therapy samples obtained for over a period of at least 6 months. | 1 month after 3 doses of vaccine | 
| Incidence of 12-month Persistent Infection associated with HPV types 31/33/45/52/58 | The endpoint of a 12-month Persistent Infection was defined to a subject was positive for the same HPV type by the HPV PCR assay to at least 1 common gene in 3 or more consecutive cervicovaginal/external genital swab, biopsy, or definitive therapy samples obtained for over a period of at least 12 months. | 1 month after 3 doses of vaccine | 
| Incidence of 6-month Persistent Infection associated with HPV types 35/39/51/56/59 | The endpoint of a 6-month Persistent Infection was defined to a subject was positive for the same HPV type by the HPV PCR assay to at least 1 common gene in 2 or more consecutive cervicovaginal/external genital swab, biopsy, or definitive therapy samples obtained for over a period of at least 6 months. | 1 month after 3 doses of vaccine | 
| Incidence of 12-month Persistent Infection associated with HPV types 35/39/51/56/59 | The endpoint of a 12-month Persistent Infection was defined to a subject was positive for the same HPV type by the HPV PCR assay to at least 1 common gene in 3 or more consecutive cervicovaginal/external genital swab, biopsy, or definitive therapy samples obtained for over a period of at least 12 months. | 1 month after 3 doses of vaccine | 
| Incidence of 6-month Persistent Infection associated with HPV types 6/11 | The endpoint of a 6-month Persistent Infection was defined to a subject was positive for the same HPV type by the HPV PCR assay to at least 1 common gene in 2 or more consecutive cervicovaginal/external genital swab, biopsy, or definitive therapy samples obtained for over a period of at least 6 months. | 1 month after 3 doses of vaccine | 
| Incidence of 12-month Persistent Infection associated with HPV types 6/11 | The endpoint of a 12-month Persistent Infection was defined to a subject was positive for the same HPV type by the HPV PCR assay to at least 1 common gene in 3 or more consecutive cervicovaginal/external genital swab, biopsy, or definitive therapy samples obtained for over a period of at least 12 months. | 1 month after 3 doses of vaccine | 
| Incidence of histopathologically confirmed genital warts related to HPV types 6, 11 | Genital warts were diagnosed by the HPV Vaccine program pathology panel from the results of cervical biopsy. HPV types 6/11 DNA was detected by PCR assay. | 1 month after 3 doses of vaccine | 
| Incidence of histopathologically confirmed cervical, and/or anal, and/or vulvar, and/or vaginal lesions cases associated with HPV types 6/11/16/18 infection detected in the cervical cytology specimen | HPV types 6/11/16/18 DNA was detected by PCR assay. Cervical, anal, vulvar, and vaginal lesions were diagnosed by the HPV vaccine program pathology panel from the results of cervical biopsy. | 1 month after 3 doses of vaccine | 
| Incidence of histopathologically confirmed cervical, and/or anal, and/or vulvar, and/or vaginal lesions cases associated with HPV types 31/33/45/52/58 infection detected in the cervical cytology specimen | HPV types 31/33/45/52/58 DNA was detected by PCR assay. Cervical, anal, vulvar, and vaginal lesions were diagnosed by the HPV vaccine program pathology panel from the results of cervical biopsy. | 1 month after 3 doses of vaccine | 
| Incidence of histopathologically confirmed cervical, and/or anal, and/or vulvar, and/or vaginal lesions cases associated with HPV types 35/39/51/56/59 infection detected in the cervical cytology specimen | HPV types 35/39/51/56/59 DNA was detected by PCR assay. Cervical, anal, vulvar, and vaginal lesions were diagnosed by the HPV vaccine program pathology panel from the results of cervical biopsy. | 1 month after 3 doses of vaccine | 
| Incidence of histopathologically confirmed cervical, and/or anal, and/or vulvar, and/or vaginal lesions cases associated with HPV types 6/11/16/18/31/33/45/52/58 infection detected in the cervical cytology specimen | HPV types 6/11/16/18/31/33/45/52/58 DNA was detected by PCR assay. Cervical, anal, vulvar, and vaginal lesions were diagnosed by the HPV vaccine program pathology panel from the results of cervical biopsy. | 1 month after 3 doses of vaccine | 
| Incidence of histopathologically confirmed cervical, and/or anal, and/or vulvar, and/or vaginal lesions cases associated with HPV types 6/11/16/18/31/33/45/52/58/35/39/51/56/59 infection detected in the cervical cytology specimen | HPV types 6/11/16/18/31/33/45/52/58/35/39/51/56/59 DNA was detected by PCR assay. Cervical, anal, vulvar, and vaginal lesions were diagnosed by the HPV vaccine program pathology panel from the results of cervical biopsy. | 1 month after 3 doses of vaccine | 
| GMC of total anti-HPV6/11/16/18/31/33/45/52/58/35/39/51/56/59 type-associated specific IgG antibodies assessed by cLIA | GMCs was as geometric mean concertration of HPV Immunoglobulin G (IgG) antibodies and was measured using a Competitive Luminex Immunoassay (cLIA). | At least 1 month after 3 doses of immunization | 
| Positive conversion rate of total anti-HPV6/11/16/18/31/33/45/52/58/35/39/51/56/59 type-associated specific IgG antibodies assessed by cLIA | Positive conversion rate of total HPV6/11/16/18/31/33/45/52/58/35/39/51/56/59 type-associated specific IgG antibodies using cLIA. | At least 1 month after 3 doses of immunization | 
| GMT of HPV6/11/16/18/31/33/45/52/58/35/39/51/56/59 type-associated neutralizing antibodies. | GMTs was defined as geometric mean titers of HPV types 6/11/16/18/31/33/45/52/58/35/39/51/56/59 determined by pseudovirus-based neutralization assay. | At least 1 month after 3 doses of immunization | 
| AEs Incidence | Adverse Events (AEs) was considered to be all adverse medical events occurring after the subject is immunized with the experimental vaccine, which may be manifested as symptoms, signs, diseases, or abnormalities in laboratory tests, but are not necessarily causal to the experimental vaccine immunization relationship | During the entire study period (From Month 0 up to Month 60) | 
| SAEs Incidence | Serious Adverse Events (SAEs) was refered to adverse medical events, e.g., death, life-threatening, permanent or serious disability or loss of function, hospitalization or prolonged hospitalization of the subject, or congenital abnormality or birth defect after receiving the investigational vaccine. In addition, other important medical events should also be considered for SAE accelerated reporting | During the entire study period (From Month 0 up to Month 60) | 
| Pregnancy outcomes in pregnant subjects( pregnancy event report form) | Previous pregnancy, current pregnancy mode, neonatal information. | During the entire study period (From Month 0 up to Month 60) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV, Vaccine