๐ฌIn plain words
What the trial is, and whether it could suit you
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.
Sign in to get the eligibility rules as simple questions to take to your doctor.
๐ Eligibility rules (as published)
Inclusion Criteria:
Subjects had to meet all of the following inclusion criteria:
1\. Aged 18 to 60 years, female.
2\. Confirmed by the central laboratory, histopathology results demonstrated cervical HSIL with concurrent HPV16 and/or HPV18 positivity.
3\. Colposcopy results during screening must meet the following criteria:
1. The colposcopy must be satisfactory, allowing clear visualization of the entire acetowhite area or the extent of suspected cervical intraepithelial neoplasia (CIN) lesions, including the upper border of the lesion.
2. If the upper border of the lesion is unclear, endocervical curettage (ECC) results must be negative.
3. The cervical lesion area must be less than 75% of the surface of the ectocervix.
4\. Fully understand the study and voluntarily sign the informed consent form, able to communicate well with the investigator and complete all treatments, examinations, and visits as required by the study protocol. The informed consent form must be signed before performing any study-specific procedures.
5\. At screening, the investigator judges the electrocardiogram (ECG) as normal or without clinically significant findings.
6\. Normal function of major organs within 1 week before the first dose: Blood routine: Hemoglobin (Hb) โฅ100 g/L; platelet count (PLT) โฅ75ร10โน/L; white blood cell count (WBC) โฅ3.0ร10โน/L; absolute neutrophil count (ANC) โฅ1.5ร10โน/L.
Liver: Total bilirubin (TB) โค1.5 ร upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) โค1.5 ร ULN; plasma albumin โฅ30 g/L.
Kidney: Serum creatinine (Scr) โค1.5 ร ULN, or creatinine clearance rate โฅ60 mL/min (calculated by Cockcroft-Gault formula) (if serum creatinine \>1.5 ร ULN).
7\. Women of childbearing potential must be willing to consistently and correctly use a contraceptive method with a failure rate of less than 1% per year from the time of signing the informed consent form until the end of the study. Acceptable methods include:
1. Hormonal contraceptives: Combined or progestin-only methods, including oral contraceptives, injections, implants, vaginal rings, or transdermal patches. Subjects with a history of hypercoagulable states (e.g., deep vein thrombosis, pulmonary embolism) must not use hormonal contraceptives.
2. Abstinence from penile-vaginal intercourse.
3. Intrauterine device (IUD) or intrauterine system (IUS).
4. Female subject's male partner sterilized for at least 6 months prior to study entry, and this male is the subject's sole sexual partner.
5. Condom use, with emergency contraception required in case of accidents such as slippage or breakage.
6. Postmenopausal patients (defined as at least 12 consecutive months of amenorrhea without alternative medical causes, with serum follicle-stimulating hormone levels within the laboratory reference range for postmenopausal women) or those sterilized for more than 12 months prior to screening may be considered not requiring contraception.
Exclusion Criteria:
Patients with any of the following were excluded from the study:
1. Any histopathologically confirmed cervical adenocarcinoma/adenocarcinoma in situ (AIS), high-grade vulvar, vaginal, or anal intraepithelial lesions or invasive cancer.
2. Female participants who are pregnant, breastfeeding, or planning to become pregnant during the study.
3. Administration of any live vaccine within 4 weeks prior to the first dose and/or any non-live vaccine within 2 weeks prior to the first dose.
4. Use of blood or blood-related products (including immunoglobulins) within 3 months prior to the first dose or planned use during the study.
5. Prior receipt of therapeutic HPV vaccines (excluding prophylactic HPV vaccines) before screening.
6. Treatment for cervical HSIL within 4 weeks prior to the first dose.
7. Presence of metal implants or implantable medical devices within the electroporation area.
8. Participation in another clinical trial within 30 days prior to screening or being in the follow-up period of another clinical trial.
9. Continuous (for more than 1 week) systemic treatment with corticosteroids (at a dose equivalent to \>10 mg/day prednisone or equivalent doses of other corticosteroids) or other immunosuppressive drugs within 30 days prior to screening, with the following exceptions.
1. Inhaled, ophthalmic, or topical use of corticosteroids at doses โค10 mg/day prednisone or equivalent is permitted.
2. Physiological corticosteroid replacement therapy at doses โค10 mg/day prednisone or equivalent is permitted.
10. History of immunodeficiency or autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, etc.) or current active autoimmune diseases requiring systemic treatment (e.g., use of disease-modifying drugs, corticosteroids, or immunosuppressive drugs).
11. Current or anticipated use of disease-modifying antirheumatic drugs (e.g., azathioprine, cyclophosphamide, cyclosporine, methotrexate) and biologic disease-modifying drugs (e.g., infliximab, adalimumab, etanercept) during the study.
12. Continuous (for more than 1 week) use of immunosuppressants such as cyclosporine, tacrolimus, azathioprine, 6-mercaptopurine, and antilymphocyte globulin, as well as other inhibitors affecting immune function (e.g., IL-6 inhibitors, TNF inhibitors, IL-17/23 inhibitors, JAK inhibitors) within 30 days prior to screening.
13. History of solid organ or bone marrow transplantation.
14. Active infections requiring systemic treatment (including active tuberculosis, active Treponema pallidum infection, and bacterial, fungal, or viral infections requiring systemic therapy).
15. Positive test results for any of the following: hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV), Treponema pallidum antibody (TP-Ab), or human immunodeficiency virus antibody (anti-HIV).
16. Participants with active herpes zoster virus infection.
17. Participants with severe dysfunction of other organs or cardiopulmonary disea