Evaluate the Safety and Immunogenicity of a 9-valent HPV Vaccine in Chinese Healthy Male Aged 9-45 Year-old

Study Overview
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Brief Summary
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To evaluate the safety and tolerability of the 9vHPV vaccine in Chinese healthy male aged 9 to 45 years.

Official Title
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Evaluate the Safety and Immunogenicity of the 9-valent Human Papillomavirus Recombinant Vaccine (Hansenula Polymorpha) in Chinese Male Aged 9-45 Years: A Randomized, Blinded and Placebo-Controlled Phase I Study

Conditions
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Penile Cancer, Anal Cancer, PIN-1, PIN-2, PIN-3, AIN1, AIN2, AIN3, Genital Wart

Intervention / Treatment
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* Biological: Placebo among 18-45 yrs
* Biological: Placebo among 9-17 yrs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Chinese male aged 9 to 45 years; Provide legal identification; For those under the age of 18, they must also provide their guardian's legal identification; Adults voluntarily agrees to enroll in this study. If the subject is a minor, both the subject and subject's legal guardian should voluntarily agree to enroll in this study and sign an informed consent form; Subjects and/or their legal guardian are able to read and understand the study schedule, and commitment to regular follow-up as required by the study; Subjects will take effective contraception from Day 0 to month 7 (For Male: celibate, wear a condom, vasectomy, etc. ; For Female Sexual Partners: use IUD, oral/injecting/Slow-release topical contraceptives (except emergency contraceptives), Hormone patches, sterilization, contraceptive diaphragm, etc. Exclusion Criteria: Subjects aged over 14 years on the day of enrolment had fever (axillary temperature≥37.3℃) within 24 hours prior to the first dose of vaccination; subjects aged≤14 had fever within 24 hours prior to the first dose of vaccination (axillary temperature≥37.5℃); Poor controlled hypertension, i.e., after lifestyle modification and/or treated (aged 9 to 17 years: systolic BP≥120mmHg and/or diastolic BP≥80mmHg; aged 18 to 45 years: Systolic BP≥140mmHg and/or diastolic BP ≥90mmHg); Had received marketed HPV vaccine; plan to receive marketed HPV vaccine during this study period; have enrolled in HPV vaccine clinical trials and have received trial vaccine/placebo; History of positive test to HPV (including types not covered by 9vHPV vaccine); History of external genital disease (e.g. genital warts, penis/perianal region/perineum intraepithelial neoplasia, penile/perianal/perineal cancer), diseases within the anus (e.g. anal intraepithelial neoplasia and anal cancer), or history of head and neck cancer; Present history of severe liver and kidney disease, severe CVDs, severe hypertension, diabetic complications, or history of malignant tumour; History of convulsions (except fever convulsions in children under 2 years of age), epilepsy, brain diseases, mental illness, or family history; With prohibitive contraindications to intramuscular injection, such as Thrombocytopenia, coagulopathy, or being treated with anticoagulants; Asplenic, functionally asplenic, or splenectomy caused by any condition; History of severe allergic reactions requiring medical intervention (e.g., anaphylactic shock, allergic laryngeal edema, Anaphylactoid purpura, thrombocytopenic purpura, local allergic necrosis reaction (Arthus reaction), etc.); History of severe side effects or a history of severe allergies to any of the components of the vaccine (Histidine, Polysorbate 80, Aluminum Phosphate Adjuvant); History of congenital/acquired immunodeficiency, such as lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, Inflammatory bowel disease, or other autoimmune diseases, etc.; Received immunosuppressive treatment within 6 months before vaccination, such as long-term glucocorticoid use (Dosage reference: equivalent to prednisone 20mg per day, more than one week); Or monoclonal antibodies; Or thymus peptides; Or interferon, etc.; Or plan to receive such products during this study period (From Day 0 to Month 7); Allow topical medication (e.g., ointments, eye drops, inhalants, or nasal sprays, etc.); Present history of infectious diseases, such as Tuberculosis (TB), Hepatitis, HIV infection, and/or TeponemaPllidum infection; Within 3 days prior to vaccination, have an acute disease or are in the acute attack of a chronic disease or have used antipyretic, analgesic and anti-allergic drugs (such as: acetaminophen, ibuprofen, aspirin, loratadine, cetirizine, etc.); Inactivated/recombinant/nucleic acid vaccines, etc. (non-attenuated vaccines) have been given within 14 days before enrollment; or have been vaccinated within 28 days of attenuated vaccines; or have received immunoglobulin products or blood-related products within 3 months before enrollment; Received other investigative or unregistered products within 30 days before vaccination or plan to receive such products during this study period; Or still participating in other clinical trial within 3 months prior to enroll this study; Plan to receive immunoglobulin products or blood-related products during this study period (From Day 0 to Month 7); Plan to relocate permanently from the area before the end of the study or leave the local area for a long time during the study visit (affecting the scheduled visit time); Abnormal laboratory testing indicators specified in study protocol (except NCS); According to the investigator's judgment, the subjects had any condition that were not suitable for participation in this study.

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The 9vHPV Recombinant Vaccine among 18-45yrs<br>Subjects received 3 doses of 9-valent HPV vaccine according to a 0, 2, 6-month schedule (0.5mL/each dose). | Biological: Placebo among 18-45 yrs<br>* Subjects received 3 doses of placebo according to a 0, 2, 6-month schedule (0.5mL/each dose).<br>|
| Experimental: The 9vHPV Recombinant Vaccine among 9-17 yrs<br>Subjects received 3 doses of 9-valent HPV vaccine according to a 0, 2, 6-month schedule (0.5mL/each dose). | Biological: Placebo among 9-17 yrs<br>* Subjects received 3 doses of placebo according to a 0, 2, 6-month schedule (0.5mL/each dose).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with Adverse Events (AEs) | Subjects with solicited and unsolicited AEs | From Day 0 to Month 7 | 
| Number of subjects with Severe adverse events (SAE) | SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. | From Day 0 to Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects receiving the 3-doses scheduled vaccination with antibody responses as assessed by Geometric mean titer (GMT) | Immunogenicity were assessed by the GMT of anti HPV6/11/16/18/33/45/52/58 neutralizing antibodies after day 31 post last dose, among the subjects who were aged 9-45 | day 31 post last dose | 
| Number of subjects receiving the 3-doses scheduled vaccination with antibody responses as assessed by seroconversion rate | Immunogenicity were assessed by the seroconversion rate of anti HPV6/11/16/18/33/45/52/58 neutralizing antibodies after day 31 post last dose, among the subjects who were aged 9-45 and seronegative before vaccination | day 31 post last dose | 
| Number of subjects receiving the 3-doses scheduled vaccination with antibody responses as assessed by IgG antibody GMT and seroconversion rate | Immunogenicity were assessed by the seroconversion rate and GMT of anti HPV6/11/16/18/33/45/52/58 IgG antibodies after day 31 post last dose, among the subjects who were aged 9-45 and seronegative before vaccination | day 31 post last dose | 
| The immunogenicity of subjects receiving 3 doses of vaccination was assessed by IgG antibodies and neutralizing antibodies | Immunogenicity were assessed by the seroconversion rate and GMT (4-fold increase rate) of anti HPV6/11/16/18/33/45/52/58 IgG and neutralizing antibodies after day 31 post last dose, among the subjects who were aged 9-45 and seropositive before vaccination | day 31 post last dose |