A Phase III Clinical Trial of a 11-valent Recombinant Human Papillomavirus Vaccine (Hansenulapolymorpha) in Chinese Women Aged 9-45 Years

Официальное название

A Multicenter Randomized, Blinded, Placebo-controlled Phase III Clinical Trial Evaluating the Protective Efficacy, Safety and Immunogenicity of a 11-valent Recombinant Human Papillomavirus Vaccine (Hansenulapolymorpha) in Chinese Women Aged 9-45 Years

Обзор

A total of 13500 Chinese women aged 18-45 years old were divided into three age groups: 18-26 years old, 27-35 years old, and 35-45 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.

Вмешательства

• Биопрепарат 11-valent recombinant human papilloma virus vaccine (Hansenula polymorpha)
  According to the 0, 2, and 6 months immunization program, intramuscular injection of the upper arm deltoid muscle, 3 doses of the experiment vaccine
• Биопрепарат placebo
  According to the 0, 2, and 6 months immunization program, intramuscular injection of the upper arm deltoid muscle, 3 doses of the placebo

Первичные конечные точки

• Person-years incidence of CIN2+ associated with HPV6/11/16/18. [Срок оценки: 1 month after 3 doses of vaccine]
• Person-years incidence of CIN2+ associated with HPV31/33/45/52/58/59/68 [Срок оценки: 1 month after 3 doses of vaccine]

Вторичные конечные точки (12)

• Person-years incidence of PI12 and PI6 associated with HPV6/11/16/18 types. [Срок оценки: 1 month after 3 doses of vaccine]
• Person-years incidence of PI12 and PI6 associated with HPV31/33/45/52/58 [Срок оценки: 1 month after 3 doses of vaccine]
• Person-years incidence of HPV6/11/16/18/31/33/45/52/58/59/68 types associated with CIN2+, CIN1+, PI12 and PI6 [Срок оценки: 1 month after 3 doses of vaccine]
• Person-years incidence of HPV6/11/16/18/31/33/45/52/58/59/68-associated anogenital and vaginal lesions (including: genital warts, VIN1+, VaIN1+, and AIN1+). [Срок оценки: 1 month after 3 doses of vaccine]
• Person-years incidence of CIN2+, PI12 and PI6 associated with HPV6/11/16/18 [Срок оценки: After at least 1 dose of vaccine]
• Person-years incidence of CIN2+, PI12 and PI6 associated with HPV31/33/45/52/58/59/68 [Срок оценки: After at least 1 dose of vaccine]
• Person-years incidence of CIN2+, CIN1+, PI12 and PI6 associated with HPV6/11/16/18/31/33/45/52/58/59/68 types. [Срок оценки: After at least 1 dose of vaccine]
• Person-years incidence of HPV6/11/16/18/31/33/45/52/58/59/68-associated anogenital and vaginal lesions (including: genital warts, VIN1+, VaIN1+, and AIN1+). [Срок оценки: After at least 1 dose of vaccine]
• AE incidence and severity distribution [Срок оценки: The first dose of vaccination to within 1 month after the full vaccination]
• AE incidence and severity distribution [Срок оценки: 0-30 days after each dose vaccination (including 30 minutes, 0-7 days, 8-30 days)]
• SAE incidence [Срок оценки: During the study，an average of 6 year]
• Number of pregnant [Срок оценки: The first dose of vaccination to within 6 months after the full vaccination]

Критерии участия

Критерии включения

\- non-gynecological related

• \*Chinese women with a history of sexual life who are 18-45 years old at the time of enrollment and can provide legal identification;
• \*Axillary body temperature <37.3℃ on the day of enrollment;
• The subjects themselves have the ability to understand the clinical trial and voluntarily sign the informed consent;
• Subjects have the ability to read, understand, and fill out research application forms such as diary cards/contact cards, and promise to follow the research requirements participate in follow-up visits;
• No previous HPV vaccination history, no commercially available HPV vaccine during the study period (about 6 years after enrollment) plan of;
• The subject has a negative urine pregnancy test on the day before vaccination.

\- Gynecology related

• \*Effective contraception was taken from day 1 of last menstrual cycle to day 0 of the study, and no childbearing within 7 months after enrollment plan.
• \*Before the gynecological visit and within 48 hours before any subsequent visit that includes a gynecological sample collection: asexual life (including same-sex or opposite-sex anal, vaginal or genital contact), unwashed/washed vagina (Except for normal bathing outside the vagina）, no vaginal drugs or preparations are used.

Критерии исключения

First dose exclusion criteria:

(Visits may be rescheduled if the criteria described in the "\*" option are met at screening)

\- Non-gynecological related

• \* Those with abnormal blood pressure (systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg) on physical examination before vaccination;
• \*3 months prior to vaccination or planned to receive any immune globulin or blood products within 7 months of enrollment;
• \*Received any vaccine within 14 days prior to vaccination, or received live vaccine within 28 days;
• \*3 days before vaccination, suffering from acute febrile illness (body temperature ≥38.5℃) or using antipyretic, analgesic and antiallergic drugs (eg: acetaminophen, ibuprofen, aspirin, loratadine, cetirizine, etc.);
• History of severe allergies/conditions requiring medical intervention (e.g. Anaphylactic shock, anaphylactic laryngeal edema, anaphylactoid purpura, thrombocytopenic purpura, local allergic necrosis(Arthus reaction) etc.);
• Immunocompromised or diagnosed with congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia Blood disease, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammation STD or other autoimmune disease;
• 1 month before vaccination or plan to receive immunosuppressive therapy within 7 months after enrollment, such as oral administration for more than 2 consecutive weeks Oral or injectable systemic corticosteroid therapy (≥2 mg/kg/day or ≥20 mg/day prednisone or equivalent to prednisone) amount); however, topical medications (such as ointments, eye drops, inhalers, or nasal sprays) are not limited;
• Previous splenectomy or impaired spleen function;
• Those with previous or current severe liver, kidney and cardiovascular diseases, complicated diabetes, and malignant tumors;
• Have a history of epilepsy, convulsions, mental illness or a family history of mental illness;
• Suffering from thrombocytopenia or any coagulation disorder that can become a contraindication to intramuscular injection;
• Participate in other clinical studies (drugs, vaccines and medical devices) within 3 months before vaccination or during the planned study period;
• The investigator believes that the subject has any other factors that are not suitable for participating in the clinical trial (such as: poor compliance or planning Permanent relocation from the area before the study is completed, etc.).

\- Gynecology related

• \*Pregnant, breastfeeding, or within 6 weeks of pregnancy at the time of the first dose of the vaccine;
• \*The subject is in the menstrual period;
• \*Acute lower genital tract infection (such as acute vulvitis/vaginitis/cervicitis, etc.) found by the naked eye during gynecological examination;
• Previous history of abnormal cervical cancer screening or lesions (including HPV DNA positive, squamous intraepithelial lesion (SIL)or atypical squamous cells of undetermined significance (ASC-US), atypical squamous epithelial cells - excluding high-grade squamous cells Intraepithelial lesions (ASC-H), atypical glandular cells (AGC) or with cervical intraepithelial neoplasia (CIN),Adenocarcinoma in situ (AIS) or cervical cancer, etc.);
• Past or current anal and genital diseases (such as vulvar intraepithelial neoplasia, vaginal intraepithelial neoplasia, genital warts,vulvar cancer, vaginal cancer and anal cancer, etc.);
• Previous hysterectomy or pelvic radiation therapy or severe cervical/vaginal dysplasia.

Exclusion criteria for 2nd and 3rd dose vaccination：

If any of the following occurs, the investigator will terminate the subject's vaccination with the investigational vaccine.

• Meet the first dose exclusion criteria 5, 6, 7, 8, 9, 12;
• Any other reasons that, in the judgment of the investigator, warrant discontinuation of the investigational vaccination.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Профилактика

Центры проведения

Китай · 8 центров

• Hechi Yizhou District Center for Disease Control and Prevention — Hechi
• Hezhou Center for Disease Control and Prevention — Hezhou
• Lianyuan Center for Disease Control and Prevention — Lianyuan
• Qiyang Center for Disease Control and Prevention — Wuxi
• Yongji Center for Disease Control and Prevention — Yongji
• Yuanqu Center for Disease Control and Prevention — Yuncheng
• Mianyang Youxian District Center for Disease Control and Prevention — Mianyang
• Neijiang Shizhong District Center for Disease Control and Prevention — Neijiang

Идентификаторы

NCT: NCT05262010 · GXIRB2021-0029-1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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