This is a randomized, double-blind, placebo controlled Phase 2 study to determine the efficacy and safety of NWRD08 administered by intramuscular (IM) injection followed by electroporation (EP) in adult women with histologically confirmed cervical high grade squamous intraepithelial lesion (HSIL) (cervical intraepithelial neoplasia grade 2 \[CIN2\] or grade 3 \[CIN3\]) associated with human papillomavirus (HPV) 16 and/or HPV18.
This is a Phase II, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of NWRD08 in patients with HPV16 and/or HPV18 positive cervical high-grade squamous intraepithelial lesion (HSIL). Eligible subjects will be randomized in a 2:2:1:1 ratio to four arms: 2 mg NWRD08, 4 mg NWRD08, and their respective matching placebo arms. Participants will receive intramuscular injections of either NWRD08 or matching placebo at the corresponding dose at Week0, 4, 8, and 16 (a total of 4 doses). Efficacy evaluations at Week 36 will include colposcopy, histopathological biopsy, cervical cytology, and HPV testing.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
150
NWRD08 delivered via IM injection + electroporation using TERESA device
Placebo delivered via IM injection + electroporation using TERESA device
Cancer Institute and Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
RECRUITINGBeijing Obstetrics and Gynecology Hospital
Beijing, Beijing Municipality, China
RECRUITINGPeking University First Hospital
Beijing, Beijing Municipality, China
Proportion of Participants with Histopathological Regression of Cervical Lesions to CIN 1 or no lesions at week 36
The number of participants with histopathologically confirmed CIN2/3 or CIN 3 associated with HPV16 or HPV18 whose cervical lesions regress to CIN 1 or no lesions at the 36 week visit.
Time frame: Week 36
Incidence and severity of local and systemic adverse events (AEs).
Adverse events (AEs) and serious adverse events (SAEs) will be monitored based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
Time frame: up to 40 weeks
Incidence and severity of adverse events (AEs) at the injection site.
Adverse events (AEs) and serious adverse events (SAEs) will be monitored based on the Guidance on Grading Standards for Adverse Events in Clinical Trials of Preventive Vaccines.
Time frame: up to 40 weeks
Incidence and severity of all serious adverse events (SAEs).
Incidence and severity of all serious adverse events (SAEs) during the study period (e.g., suspected unexpected serious adverse reactions, unexpected adverse device effects).
Time frame: up to 40 weeks
Pregnancy occurrences and outcomes during the study period
Time frame: up to 40 weeks
Incidence of investigational product-related adverse events (AEs) leading to treatment discontinuation.
Time frame: up to 40 weeks
Incidence of Grade 3 or higher adverse events (AEs) related to the investigational product.
Time frame: up to 40 weeks
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Peking Union Medical College Hospital
Beijing, Beijing Municipality, China
RECRUITINGThe Second Hospital of Shanxi Medical University
Taiyuan, Shanxi, China
RECRUITINGProportion of Participants with Histopathological Regression to no lesions.
The number of participants with histopathologically confirmed CIN2/3 or CIN 3 associated with HPV16 or HPV18 whose cervical lesions regress to no lesions at the 36 week visit.
Time frame: Week 36
Proportion of Participants with Histopathological Regression to LSIL/CIN1.
The number of participants with histopathologically confirmed CIN2/3 or CIN 3 associated with HPV16 or HPV18 whose cervical lesions regress to LSIL/CIN1 at the 36 week visit.
Time frame: Week 36
Proportion of Participants with Virologically-proven Clearance of HPV 16 and/or HPV18.
The number of participants with virologically-proven clearance of HPV16 and/or HPV18 at the 36 week visit.
Time frame: Week 36
Proportion of Participants with Virologically-proven Clearance of HPV 16 or HPV18 or Histopathological Regression of Cervical Lesions to LSIL/CIN 1 or no lesion.
The number of participants with Virologically-proven Clearance of HPV 16 or HPV18 or Histopathological Regression of Cervical Lesions to LSIL/CIN 1 or no lesion at the 36 week visit.
Time frame: Week 36
Proportion of Participants with Virologically-proven Clearance of HPV 16 or HPV18 in Combination with Histopathological Regression of Cervical Lesions to LSIL/CIN 1 or no lesion.
The number of participants with Virologically-proven Clearance of HPV 16 or HPV18 in Combination with Histopathological Regression of Cervical Lesions to LSIL/CIN 1 or no lesion at the 36 week visit.
Time frame: Week 36
Proportion of Participants with Virologically-proven Clearance of HPV 16 or HPV18 in Combination with Histopathological Regression of Cervical Lesions to no lesion.
The number of participants with Virologically-proven Clearance of HPV 16 or HPV18 in Combination with Histopathological Regression of Cervical Lesions to no lesion at the 36 week visit.
Time frame: Week 36
Levels of cellular immune responses.
Levels of cellular immune responses measured by interferon-gamma enzyme-linked immunospot (IFN-γ ELISPOT) assay in peripheral blood mononuclear cells (PBMCs) of subjects at baseline and at Week 10, 18, 24, and 36 after first dose.
Time frame: Week 10, 18, 24, and 36
Levels of serum anti-HPV16 and anti-HPV18 antibody titers.
Levels of serum anti-HPV16 and anti-HPV18 antibody titers measured in peripheral blood samples collected at baseline and at Week 10, 18, 24, and 36 after initial vaccination.
Time frame: Week 10, 18, 24, and 36