DNA vaccine for treating cervical lesions caused by HPV-16 and HPV-18

Phase I Safety and Tolerability Study of NWRD08 in HPV-16 and/or HPV-18 Related Cervical High-grade Squamous Intraepithelial Lesion (HSIL) Patients

This study is testing a new DNA vaccine to see if it can safely treat cervical lesions caused by HPV-16 and HPV-18 in patients with high-grade lesions.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years to 60 Years
• Sex: Female
• Sponsor: Newish Technology (Beijing) Co., Ltd. (Industry-sponsored)
• Drugs / interventions: infliximab, adalimumab, methotrexate, cyclophosphamide, prednisone
• Locations: 1 site (Beijing, Beijing)
• Trial ID: NCT06276101 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and tolerability of a DNA plasmid vaccine, NWRD08, targeting HPV-16 and HPV-18 in patients with high-grade squamous intraepithelial lesions (HSIL). It is a single-arm, open-label Phase 1 study that administers the vaccine through electroporation in three different dose groups: 1mg, 4mg, and 8mg. The study will determine the maximum tolerated dose using a 3+3 dose escalation schedule, with a total of 9 to 18 participants. Follow-up assessments will include colposcopy and biopsy at week 12, with additional safety monitoring for 28 days post-treatment.

Who should consider this trial

Good fit: Ideal candidates for this study are females aged 18 to 60 with histopathologically confirmed HPV-16 and/or HPV-18-related cervical HSIL.

Not a fit: Patients with other types of cervical lesions or those who do not have HPV-16 or HPV-18 infections may not benefit from this study.

Why it matters

Potential benefit: If successful, this vaccine could provide a novel therapeutic option for patients with HPV-related cervical HSIL, potentially reducing the need for invasive procedures.

How similar studies have performed: While there have been studies on HPV vaccines, this specific approach using a DNA plasmid vaccine for HSIL is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Female aged between 18 and 60 years;
2. histopathological examination/biopsy confirmed HPV-16 and/or HPV-18-associated cervical High-grade squamous intraepithelial lesion (HSIL);
3. The electrocardiograms deemed normal or with abnormalities not considered clinically significant by the site investigators.
4. Major organ functions were normal within 1 week before the first NWRD08 administration: 1) Blood routine: Hemoglobin (Hb) ≥100 g/L; Platelet count (PLT) ≥75×109/L; 2) The liver: Total bilirubin (TB) ≤1.5× upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; Plasma albumin ≥30 g/L; 3)Kidney: Serum creatinine (Scr) ≤1.5×ULN, or creatinine clearance ≥40 mL/min (serum creatinine \> 1.5 x ULN);
5. Within 1 week before the first NWRD08 administration, women of childbearing age must have a negative serum pregnancy test and consent to use effective contraception form the signing of the ICF to the end of the study.
6. Have fully understood the study and voluntarily signed the ICF, have good communication with the investigator, and are able to complete all treatments, examinations, and visits stipulated in the study protocol.

Exclusion Criteria:

1. Microscopic or gross evidence of adenocarcinoma-in-situ (AIS), high grade vulvar, vaginal, or anal intraepithelial neoplasia or invasive cancer in any histopathologic specimen at screening;
2. Pregnant, breastfeeding or considering becoming pregnant during the study;
3. Administration of any non-live vaccines within 2 weeks prior to the first NWRD08 administration;
4. Administration of any live vaccines within 4 weeks prior to the first NWRD08 administration;
5. Treatment for cervical HSIL within 4 weeks prior to the first NWRD08 administration;
6. Any metallic implants/implanted electric devices around the intended sites of electroporation (deltoid muscles);
7. Participated in another clinical trial or was under observation in another clinical trial within 30 days prior to screening;
8. Continuous (more than 1 week) glucocorticoid therapy (dose equivalent to prednisone \> 10 mg/ day) within 30 days prior to screening, except hormone replacement therapy, intratracheal, ocular and topical administration;
9. A history of immune deficiency or autoimmune diseases (e.g., rheumatoid joint disease, systemic lupus erythematosus, multiple sclerosis, etc.);
10. Current or intended use of disease-modifying antirheumatic drugs (e.g., azathioprine, cyclophosphamide, cyclosporin and methotrexate) and biologic drugs (e.g., infliximab, adalimumab and etanercept);
11. Continuous (more than 1 week) use of immunosuppressive agents. (e.g., cyclosporin, tacrolimus, azathioprine, 6-mercaptoputine and antilymphocyte globulin, etc.);
12. Patients with a history of solid organ or bone marrow transplantation;
13. With uncontrolled severe infection (\> grade 2 NCI-CTCAE adverse events, version 5.0);
14. Patients with a history of human immunodeficiency virus (HIV) infection or carriers of syphilis;
15. Patients who are found to have active zoster virus infections;
16. Patients with serious other organ dysfunction or cardiopulmonary diseases;
17. Epilepsy that requires treatment with medication (e.g. steroids or antiepileptic drugs);
18. Had or currently has other malignancies (with the exception of adequately treated and completely cured ductal carcinoma in situ of the breast, carcinoma in situ of the cervix, basal cell carcinoma of the skin, superficial bladder tumor, or any malignancy that was cured more than 5 years before study entry);
19. A known history of albumin allergy, or severe allergy, or allergic disease, or allergic constitution, or severe iodine contrast allergy, meeting any of these criteria;
20. Patients with clinically significant heart disease or medical history;
21. Severe mental illness;
22. A history of drug or alcohol abuse;
23. Pregnant or lactating women, or women of childbearing age with positive blood pregnancy tests, or women of reproductive age and their spousal not willing to use contraception during and up to 6 months following completion of the study;
24. Patients deemed by the investigator to be ineligible for this clinical trial.

Where this trial is running

Beijing, Beijing

• Peking Union Medical College Hospital — Beijing, Beijing, China (Recruiting)

Study contacts

• Principal investigator: Yang Xiang, M.D. — Peking Union Medical College Hospital
• Study coordinator: Fang Jiang, M.D.

Conditions High-grade Squamous Intraepithelial Lesion; NWRD08; DNA Vaccine; HPV16; HPV18; HSIL