This is a single-arm, open label, multi-center Phase 1 clinical study to evaluate the safety and tolerability of HPV-16 and HPV-18-targeted DNA plasmid vaccine (NWRD08) in patients HPV-16 and/or HPV-18 related cervical HSIL.
This study is divided into three dose groups:1mg, 4mg, and 8mg. Each patient will be administered NWRD08 by electroporation in entire study period. The Maximum Tolerated Dose of NWRD08 will be determined by the classical 3+3 dose escalation schedule. The number of patients will be ranged from 9 to 18. After the completion of treatment, the subjects shall continue to receive safety follow-up until 28 days after the last administration. Colposcopy and biopsy were performed at week 12, if HSIL was identified, loop electro-surgical excisional procedure (LEEP) or cold Knife conization (CKC) will be performed when necessary. The subjects were then followed up at week 36 and all adverse events shall revert to level I or all adverse events shall be clinically stable (whichever is later achieved).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
9
DNA plasmid delivered via IM injection + electroporation using TERESA device
Peking Union Medical College Hospital
Beijing, Beijing Municipality, China
RECRUITINGSafety
All adverse events (AE) will be determined based on the rate and severity grade of events, including incidence and severity of serious adverse events (SAE) (according to NCI-CTCAE Standard version 5.0 of common Terms for Adverse Events). The grade of injection-site AEs will be determined on the basis of the Guidelines for Adverse Event Classification Standards for Clinical Trials of Preventive Vaccines (2019) issued by the National Medical Products Administration.
Time frame: From first administration of NWRD08 to 24 weeks (Week36) after the last administration.
Dose-limiting toxicity (DLT)
t would be determined based on the rate and severity grade of events or abnormalities through evaluating systemic or local adverse events, clinical laboratory test results, vital signs that is definitely, probably, or possibly related to the test drug occurring within 28 days of the last dosing will be classified as DLT during dosing climb.
Time frame: From first administration of NWRD08 to 28 days after the last administration
Immunogenicity
Immunologic reactogenicity by measuring HPV16/18 E6/E7 specific T cell response (IFN-γ ELISPOT) and anti-HPV16/18 E6/E7antibodies (ELISA) in blood samples.
Time frame: At week 0, week 2, week 4, week 6, week 8, week 10, week 12 and week 36.
Histopathology outcome and HPV Viral clearance
Number of subjects with virologically-proven clearance of HPV 16 or 18 and number of subjects with histopathological regression of cervical lesions to CIN 1 or normal.
Time frame: Week 12
The recommended phase II dose (RP2D)
The recommended phase II dose (RP2D) was selected on the basis of tolerability during the safety expansion.
Time frame: Week 12
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