Phase IIIb Clinical Trial of Quadrivalent Recombinant Human Papillomavirus Vaccine (Hansenulapolymorpha) for Age/Immunization Schedule Bridging

A Randomized, Open-label, Non-inferiority Phase IIIb Clinical Trial to Evaluate the Immunogenicity Age/Schedule Bridging Between Adolescent Girls Aged 9-14 Years Receiving a 2-dose Regimen or Adolescent Girls Aged 9-17 Years Receiving a 3-dose Regimen of a Quadrivalent Recombinant Human Papillomavirus (HPV) Vaccine (Hansenula Polymorpha) and Women Aged 18-35 Years.

This vaccine was jointly developed by Chengdu Institute of Biological Products Co., Ltd. and National Vaccine and Serum Institute, China, is co-sponsoring this clinical trial.

This trial plans to enroll 1,800 female subjects aged 9-35 years, 450 in each of the 18-25 years old 3-dose group, 26-35 years old 3-dose group, 9-17 years old 3-dose group and 9-14 years old 2-dose group.

All subjects in the 9-14 years old 2-dose group will be injected with 2 doses of the experimental vaccine in the deltoid muscle of the upper arm according to the 0-6 month immunization schedule. Subjects in the non-immune persistence subgroup will need to complete 6 on-site visits and subjects in the immune persistence subgroup will need to complete 13 on-site visits ; All subjects in the 9-17 years old 3-dose group and the 18-35 years old 3-dose group will be injected with 3 doses of the experimental vaccine in the deltoid muscle of the upper arm according to the 0, 2, and 6 month immunization schedule. Subjects in the non-immune persistence subgroup will need to complete 9 on-site visits and subjects in the immune persistence subgroup will need to complete 16 on-site visits

Study Overview

• Status: Active, not recruiting
• Conditions: Human Papillomavirus (HPV) Infection; HPV (Human Papillomavirus)-Associated Carcinoma
• Intervention / Treatment: Biological: 3 doses of vaccine Quadrivalent Recombinant Human Papillomavirus Vaccine (Hansenulapolymorpha); Biological: 2 doses of vaccine Quadrivalent Recombinant Human Papillomavirus Vaccine (Hansenulapolymorpha)

• Study Type: Interventional
• Enrollment (Actual): 1800
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shandong
    • Heze, Shandong, China
      • Shanxian Center for Disease Control and Prevention
    • Liaocheng, Shandong, China
      • Liaocheng Center for Disease Control and Prevention
    • Tai’an, Shandong, China
      • Daiyue District Center for Disease Control and Prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Females aged 9-35 years at the time of enrollment;
• Subjects aged 9-17 years at the time of enrollment and at least one legal guardian are informed and willing to participate, sign the informed consent form and can provide valid identity documents; subjects aged 18-35 years at the time of enrollment are informed and willing to participate, sign the informed consent form and can provide valid identity documents;
• Subjects are able to understand the research procedures and cooperate with the requirements of the clinical trial to participate in regular follow-up;
• Female subjects of childbearing age have a negative urine pregnancy test on the day of enrollment, are not breastfeeding and have no fertility plans within 7 months after enrollment; have taken effective contraceptive measures since the end of the last menstruation until enrollment, and agree to continue to use effective contraceptive measures within 7 months after participating in the study (effective contraceptive measures include: oral contraceptives, injections or implants, sustained-release local contraceptives, hormone patches, intrauterine devices (IUDs), sterilization, abstinence, condoms (male), diaphragms, cervical caps, etc.);
• Body temperature ≤37.0℃ (axillary temperature) on the day of enrollment.

Exclusion Criteria:

First dose exclusion criteria

• Those who have received a commercially available HPV vaccine in the past or plan to receive a commercially available HPV vaccine during the study; or have participated in other HPV vaccine clinical trials and have received the vaccine/placebo;
• Those who have a history of cervical lesions that are likely to be related to HPV infection (such as abnormal cervical cancer screening, CIN disease history); Those who have a history of hysterectomy or pelvic radiotherapy; Patients who have a history of external genital diseases that are likely to be related to HPV infection (such as vulvar intraepithelial neoplasia, vaginal intraepithelial neoplasia, and genital warts);
• Those who have a history of severe allergic reactions to any vaccine or drug (including yeast) that require medical intervention, such as anaphylactic shock, allergic laryngeal edema, allergic purpura, thrombocytopenic purpura, local allergic necrosis reaction (Arthus reaction), etc.Or individuals with a known hypersensitivity to any of the components of the test vaccine (L-histidine, sodium chloride, aluminum hydroxide, and water for injection);
• Those who have impaired immune function or have been diagnosed with congenital or acquired immunodeficiency, human immunodeficiency virus (Human Immunodeficiency Virus). Virus, HIV) infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease or other autoimmune diseases;
• Those who have received long-term (≥14 days) immunomodulatory therapy (including immune enhancers and immunosuppressants) within 1 year prior to vaccination or within 7 months after enrollment, such as oral or injectable systemic glucocorticoid therapy (≥14 days, dose ≥2 mg/kg/day or ≥20 mg/day prednisone or equivalent prednisone dose), are permitted to use topical medications (such as ointments, eye drops, inhalers or nasal sprays), but topical medications must not exceed the dose recommended in the instructions or have any signs of systemic exposure;
• Any immunoglobulin or blood products within 3 months before vaccination or planned within 7 months after enrollment;
• Those who have received a non-live vaccine within 14 days prior to vaccination, or a live vaccine within 28 days prior to vaccination;
• Acute onset or use of antipyretic, analgesic and antiallergic drugs (such as acetaminophen, ibuprofen, aspirin, loratadine, cetirizine, etc.) 3 days before vaccination, or acute attack of chronic diseases;
• History of convulsions (except febrile convulsions), or history or family history of epilepsy, encephalopathy, mental illness;
• Past or current severe (such as emergency treatment, surgical treatment, etc.) heart disease (such as congenital heart disease, etc.), liver and kidney disease (such as chronic hepatitis or suspected active hepatitis, nephrotic syndrome, uremia, etc.), complications of diabetes, malignant tumors, etc.;
• Elevated blood pressure measured by on-site physical examination (9-15 years old: systolic blood pressure ≥100+1.5×age (years) mmHg and/or diastolic blood pressure ≥65+age (years) mmHg; 16-26 years old: systolic blood pressure ≥140mmHg and/or diastolic blood pressure ≥90mmHg);
• Participating in clinical studies of other investigational or unmarketed products (drugs, vaccines and medical devices) within 3 months before vaccination or planning to participate in the study period;
• Asplenia or functional asplenia, or splenectomy caused by any circumstances;
• Suffering from thrombocytopenia or other coagulation disorders that may be contraindications to intramuscular injection;
• Any other factors that the researcher believes make the subject unsuitable for participation in clinical trials.

Subsequent doses of vaccination should be postponed if any of the following conditions occur. Delays should ideally be made within the prescribed time window:

• Axillary temperature >37.0℃ before vaccination;
• Received any immunoglobulin or blood products within 3 months prior to vaccination;
• Received a non-live vaccine within 14 days prior to vaccination, or a live vaccine within 28 days prior to vaccination;
• Acute onset of illness or use of antipyretics, analgesics, and antihistamines (such as acetaminophen, ibuprofen, aspirin, loratadine, cetirizine, etc.) within 3 days prior to vaccination, or an acute exacerbation of a chronic disease;
• Any other reason deemed necessary for postponement by the investigator.

If any of the following situations occur, the researcher will terminate the subsequent doses of vaccination for the subject.

• Positive urine pregnancy test before vaccination (on the day of vaccination); Note: If the subject chooses to terminate the pregnancy, at least 6 weeks after the end of the pregnancy and can submit medical evidence of termination of pregnancy (such as imaging reports or relevant medical records, etc.), the researcher can continue to vaccinate if it is considered that the subject can continue to vaccinate; if the subject chooses to continue the pregnancy, the subsequent doses of vaccination will not be administered.
• Newly discovered or newly occurring situations that meet the first dose exclusion criteria 1, 2, 3, 4, 9, 10, 13, and 14;
• After vaccination, adverse reactions related to vaccination are evaluated and considered unsuitable for continued vaccination;
• Any other reasons that the researcher assesses to terminate vaccination.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 9-17 years old 3 doses group	Biological: 3 doses of vaccine Quadrivalent Recombinant Human Papillomavirus Vaccine (Hansenulapolymorpha); Three doses of the experimental vaccine were injected into the deltoid muscle of the upper arm according to the immunization schedule at 0, 2, and 6 months.
Experimental: 9-14 years old 2 doses group	Biological: 2 doses of vaccine Quadrivalent Recombinant Human Papillomavirus Vaccine (Hansenulapolymorpha); Two doses of the experimental vaccine were injected into the deltoid muscle of the upper arm according to the immunization schedule at 0 and 6 months.
Experimental: 18-25 years old 3 doses group	Biological: 3 doses of vaccine Quadrivalent Recombinant Human Papillomavirus Vaccine (Hansenulapolymorpha); Three doses of the experimental vaccine were injected into the deltoid muscle of the upper arm according to the immunization schedule at 0, 2, and 6 months.
Experimental: 26-35 years old 3 doses group	Biological: 3 doses of vaccine Quadrivalent Recombinant Human Papillomavirus Vaccine (Hansenulapolymorpha); Three doses of the experimental vaccine were injected into the deltoid muscle of the upper arm according to the immunization schedule at 0, 2, and 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Geometric mean titers (GMTs) of neutralizing antibodies against HPV types 6, 11, 16, and 18 among subjects who were seronegative at baseline (pre-vaccination)	1 month after completion of the vaccination series

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with a ≥4-fold rise in neutralizing antibody titers against HPV types 6, 11, 16, and 18 among subjects who were seronegative at baseline (pre-vaccination)		1 month after completion of the vaccination series
Geometric mean fold rise (GMFR) of neutralizing antibodies against HPV types 6, 11, 16, and 18 among participants who were seronegative at baseline (pre-vaccination)		1 month after completion of the vaccination series
Geometric Mean Titers (GMTs) of neutralizing antibodies against HPV types 6, 11, 16, and 18 at 1 month after completion of the vaccination series among participants who were seropositive at baseline (pre-vaccination).		1 month after completion of the vaccination series
Geometric mean fold rise (GMFR) of neutralizing antibodies against HPV types 6, 11, 16, and 18 among participants who were seropositive at baseline (pre-vaccination)		1 month after completion of the vaccination series
Proportion of participants with a ≥4-fold rise in neutralizing antibody titers to HPV types 6, 11, 16, and 18 among participants who were seropositive at baseline (pre-vaccination)		1 month after completion of the vaccination series
Geometric mean titers (GMTs) of neutralizing antibodies against HPV types 6, 11, 16, and 18 in all subjects		1 month after completion of the vaccination series
Geometric mean fold rise (GMFR) of neutralizing antibodies against HPV types 6, 11, 16, and 18 in all subjects		1 month after completion of the vaccination series
Proportion of subjects with a ≥4-fold rise in neutralizing antibody titers against HPV types 6, 11, 16, and 18 in all subjects		1 month after completion of the vaccination series
Geometric mean titers (GMTs) of neutralizing antibodies against HPV types 6, 11, 16, and 18 in all subjects		6, 12, 24, 36, 48, 60, and 72 months after completion of the vaccination series
Seropositivity rate of neutralizing antibodies against HPV types 6, 11, 16, and 18 in all subjects		6, 12, 24, 36, 48, 60, and 72 months after completion of the vaccination series
The number of cases of AE（Adverse Event）		From the first vaccination through 1 month after completion of the vaccination series
The incidence of AEs leading to subjects withdrawing from clinical trials		From the first vaccination through 1 month after completion of the vaccination series
Distribution of severity of AE		From the first vaccination through 1 month after completion of the vaccination series
The incidence of AEs		Within 0-30 days after each vaccination (including 30 minutes, 0-7 days, and 8-30 days) and >30 days after each vaccination
Distribution of severity of AE		Within 0-30 days after each vaccination (including 30 minutes, 0-7 days, and 8-30 days) and >30 days after each vaccination
The incidence of SAE		From the first vaccination through 6 months after completion of the vaccination series
Collect information about previous pregnancies of pregnant women survey	Such as previous pregnancy, current pregnancy mode, etc	From the first vaccination through the end of the study（Approximately 72 months）
Obtain pregnancy outcomes in pregnant subjects survey	Collecting newborn information	From the first vaccination through the end of the study（Approximately 72 months）

Collaborators and Investigators

• Sponsor: National Vaccine and Serum Institute, China
• Collaborators: Chengdu Institute of Biological Products Co.,Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2025
• Primary Completion (Estimated): July 1, 2032
• Study Completion (Estimated): July 1, 2032

Study Registration Dates

• First Submitted: October 8, 2024
• First Submitted That Met QC Criteria: October 8, 2024
• First Posted (Actual): October 9, 2024

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: hpv; hpv vaccine
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Disease Attributes; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; DNA Virus Infections; Tumor Virus Infections; Pathological Conditions, Signs and Symptoms; Infections; Papillomavirus Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: CNBG-CD-022-CT-4-Ⅲb

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No