NWRD08 DNA Plasmid for HPV-16 and/or HPV-18 Related Cervical HSIL

NCT06276101 | Recruiting Phase 1

• 1 other identifier: NEWISH-HPV-101
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

High-grade Squamous Intraepithelial Lesion (HSIL)

Keywords

NWRD08; DNA Vaccine; HPV16; HPV18; HSIL

Outcome Measures

Primary Outcomes (2)

• Safety

  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.

  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.

  From first administration of NWRD08 to 28 days after the last administration

Secondary Outcomes (3)

• Immunogenicity

  At week 0, week 2, week 4, week 6, week 8, week 10, week 12 and week 36.

• Histopathology outcome and HPV Viral clearance

  Week 12

• The recommended phase II dose (RP2D)

  Week 12

Study Arms (1)

NWRD08 administered by electroporation

EXPERIMENTAL

Patients will be assigned to 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.

Biological: NWRD08 administered by electroporation

Interventions

NWRD08 administered by electroporation BIOLOGICAL

DNA plasmid delivered via IM injection + electroporation using TERESA device

NWRD08 administered by electroporation

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female aged between 18 and 60 years;
• histopathological examination/biopsy confirmed HPV-16 and/or HPV-18-associated cervical High-grade squamous intraepithelial lesion (HSIL);
• The electrocardiograms deemed normal or with abnormalities not considered clinically significant by the site investigators.
• 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);
• 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.
• 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.

You may not qualify if:

• 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;
• Pregnant, breastfeeding or considering becoming pregnant during the study;
• Administration of any non-live vaccines within 2 weeks prior to the first NWRD08 administration;
• Administration of any live vaccines within 4 weeks prior to the first NWRD08 administration;
• Treatment for cervical HSIL within 4 weeks prior to the first NWRD08 administration;
• Any metallic implants/implanted electric devices around the intended sites of electroporation (deltoid muscles);
• Participated in another clinical trial or was under observation in another clinical trial within 30 days prior to screening;
• 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;
• A history of immune deficiency or autoimmune diseases (e.g., rheumatoid joint disease, systemic lupus erythematosus, multiple sclerosis, etc.);
• 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);
• Continuous (more than 1 week) use of immunosuppressive agents. (e.g., cyclosporin, tacrolimus, azathioprine, 6-mercaptoputine and antilymphocyte globulin, etc.);
• Patients with a history of solid organ or bone marrow transplantation;
• With uncontrolled severe infection (\> grade 2 NCI-CTCAE adverse events, version 5.0);
• Patients with a history of human immunodeficiency virus (HIV) infection or carriers of syphilis;
• Patients who are found to have active zoster virus infections;

Sponsors & Collaborators

• Newish Technology (Beijing) Co., Ltd.: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

MeSH Terms

Conditions

Squamous Intraepithelial Lesions

Condition Hierarchy (Ancestors)

Morphological and Microscopic Findings; Pathological Conditions, Signs and Symptoms

Study Officials

• Yang Xiang, M.D.

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fang Jiang, M.D.

CONTACT

86-010-69155635; 13671170943@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2024
• First Posted: February 23, 2024
• Study Start: January 25, 2024
• Primary Completion: December 30, 2024
• Study Completion: July 30, 2025
• Last Updated: February 23, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: starting 6 months after publication
• Access Criteria: by publication

Locations

CN (1)