High-grade squamous intraepithelial lesions associated with human papillomavirus type 16/18
Conditions
Interventions
Different dose intervention groups:SYS6026 injection was administered subcutaneously in four dose groups of 50 µg, 100µg, 150 µg, and 200 µg
Sponsors
Peking University People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Aged >= 18 years; 2. Confirmed HPV type 16 and/or 18 associated HSIL, including cervical, vulvar, vaginal, or anal; unwilling to received surgery or failure of medication (eg: 5% imiquimod cream, 1% cidofoviur gel, etc) 3. Pathological diagnosis of Grade 2 or 3 CIN, VIN, VAIN, AIN and other HSIL by colposcopy or anoscopy at local hospital (the time to obtain lesion specimens was within 4 weeks before the first vaccination). Agree to provide biological samples during the study; 4. Adequate organ function within 1 week before the first vaccination: a. Bone marrow function: Hb>=100 g/L; PLT>=100×10^9/L; Neutrophil count >=1.5×10^9/L; b. Hepatic function: TB=30 g/L; c. Renal function: Scr=60 mL/min (calculated by Cockcroft-Gault formula); d. Coagulation function: PT, APTT and INR<=1.5×ULN; 5. Normal electrocardiogram or abnormal values without clinical significance; 6. Normal vital signs: a. Axillary body temperature <=37.0? on the day of the first vaccination; b. Systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg; 7. Women of child-bearing potiental agree to use a reliable method of contraception (hormonal contraceptives, barrier methods, or abstinence) or have a partner who is sterile during the trial period and for at least 1 year after the last vaccination; Female participants of reproductive age must have had a negative blood pregnancy test within 7 days prior to enrollment; 8. Fully understood and signed writen informed consent.
Exclusion criteria
Exclusion criteria: 1. During the screening period cytological or pathological diagnosed AIS, AGC-FN, invasive carcinoma, etc.; 2. Have received HSIL treatment within 4 weeks prior to initial vaccination; 3. Have received previous HPV vaccine treatment (approved prophylactic HPV vaccine is allowed); 4. Have received any live vaccine injection within 4 weeks or any non-live vaccine injection within 2 weeks prior to the first vaccination; 5. Previous or current other malignancies (except for completely cured breast ductal carcinoma in situ, skin basal cell carcinoma, non-muscle invasion bladder tumor, or any malignancies cured more than 5 years); 6. Have a history of active autoimmune disease; 7. Other immune function abnormalities, such as those with immunoenhancement or immunosuppressive therapy within 3 months (continuous oral or intravenous administration for more than 14 days); Or have received whole blood, plasma and immunoglobulin treatment within 1 month; Or have a known impairment or low immunological function, or any condition resulting in functional asplenia or splenectomy; 8. Have a history of severe allergies, or a history of allergic diseases, or are an allergic constitution; 9. Have participating in other clinical trials within 4 weeks prior to the first vaccination; 10. Have received major surgery or significant trauma within 4 weeks prior to the first vaccination; 11. Have a fever (axillary temperature >=38.0?) within 3 days or have a acute illness or acute eposide of chronic disease within 5 days or use of antipyretic, analgesic, anti-allergic drugs within 3 days before the first vaccination; 12. Have a active hepatitis B (hepatitis B virus titer >1000 copies /mL or 200 IU/mL) or Hepatitis C virus infection; 13. Have a history of immunodeficiency, or HIV antibody test positive; 14. Have bacterial, fungal or viral infections and received systemic antibiotion treatment ; 15. Have received long-term (>=7 days) systemic use of corticosteroids (prednisone >=20 mg/ day or equivalent) or other immunosuppressive therapy (allowing short-term use of corticosteroids for prophylactic treatment; Topical use of glucocorticoids is permitted, e.g., ocular, intra-articular, intranasal, and inhaled). Current or intended use of anti-rheumatoid or immunomodulatory drugs, such as azathioprine, cyclophosphamide, cyclosporin, methotrexate, and TNF-a inhibitors (such as infliximab, adalimumab, or Etanercep); 16. Have a history of organ transplantation or bone marrow transplantation; 17. Female participants in pregnancy or lactation; 18. Other circumstances that may interfere with study process or affect the study outcome or any other illness or condition of clinical significance that investigators deems unsuitable to participate in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence and severity of AE; | — |
Secondary
| Measure | Time frame |
|---|---|
| The immunogenicity of SYS6026 injection: specific cytotoxic T cell (CTL) killing activity, anti-HPV16 E6/E7, anti-HPV18 E6/E7 antibody titers;The proportion of subjects with histopathological regression to CIN1 or normal and clearance of HPV16 or HPV18;Exogenous mRNA exposure levels in plasma (e.g. AUC, Cmax, etc.);Biomarkers: IL-1ß, IL-6, TNF-a, IFN-?, and T lymphocyte infiltration in tissues, et; | — |
Countries
China
Contacts
Public ContactWang Jianliu; Fang Yi
Peking University People's Hospital
Outcome results
None listed