NWRD09 for Persistent Cervical HPV16 Infection

Official title

A Randomized, Double-Blind, Placebo-Controlled Clinical Study Evaluating the Efficacy and Safety of NWRD09 in Patients With Persistent Cervical HPV16 Infection

Overview

This is a randomized, double-blind, placebo controlled study to determine the efficacy and safety of NWRD09 in adult women with persistent cervical HPV16 infection.

Detailed description

This is a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of NWRD09 in patients with persistent cervical HPV16 infection who may or may not have concomitant cervical LSIL. Eligible participants will be randomized in a 1:1 ratio to two groups: NWRD09 and placebo.

Participants will receive intramuscular injections of either NWRD09 or placebo at the corresponding dose at weeks 0, 2, 4, and 12 (a total of 4 doses).

Efficacy evaluations at Week 16 will include cervical cytology and HPV testing.

Interventions

• Biological NWRD09/ Placebo administered by IM injection
  NWRD09/ Placebo

Primary outcome measures

• Proportion of participants with virologically-proven clearance of HPV 16 at week 16. [Time frame: Week 16]

Secondary outcome measures (5)

• Incidence and severity of local and systemic adverse events (AEs). [Time frame: up to 36 weeks]
• Proportion of participants with virologically-proven clearance of HPV 16 at week 28. [Time frame: Week 28]
• Proportion of participants with virologically-proven clearance of HPV 16 at weeks 16 and 28. [Time frame: Weeks 16、28]
• Proportion of participants with baseline cervical LSIL showing histopathological regression to no lesions at 28 weeks after the first dose. [Time frame: Week 28]
• Levels of cellular immune responses. [Time frame: Weeks 6, 16 , 28]

Eligibility criteria

Inclusion criteria

• Female, aged 45 to 65 years (inclusive).
• Documented positive result for HPV 16 from a cervical sample collected at screening, with a confirmed duration of positivity for at least 12 months before screening.
• Satisfactory colposcopy examination. For participants with concomitant cervical LSIL, the entire aceto-white staining area or the suspected cervical intraepithelial neoplasia (CIN) lesion, including the upper border of the transformation zone, must be fully visualized.
• Adequate organ function within 1 week before the first dose, defined as:

1\) Hematology: Hemoglobin (Hb) ≥ 100 g/L; Platelet count (PLT) ≥ 75 × 10⁹/L; Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L.

2\) Hepatic: Total bilirubin (TB) ≤ 1.5 × Upper Limit of Normal (ULN); Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 1.5 × ULN; Plasma albumin ≥ 30 g/L.

3\) Renal: Serum creatinine (Scr) ≤ 1.5 × ULN, or calculated creatinine clearance ≥ 60 mL/min (using the Cockcroft-Gault formula) \[for participants with serum creatinine > 1.5 × ULN\].

(5) For premenopausal women of childbearing potential: a negative serum pregnancy test within 7 days before the first dose. Eligible participants of childbearing potential and their partners must agree to use highly effective contraception throughout the trial and for 6 months after the last study dose (at Week 12).

(6) Ability to understand the study and voluntarily provide written informed consent (ICF), willingness and ability to communicate effectively with the investigator, and to comply with all protocol-required treatment, examinations, and visits.

Exclusion criteria

• Any histopathologically confirmed cervical adenocarcinoma/adenocarcinoma in situ (AIS), high-grade cervical, vulvar, vaginal, or anal intraepithelial neoplasia, or invasive cancer.
• Cervical cytology results indicating ASC-H (Atypical Squamous Cells - cannot exclude HSIL), HSIL (High-grade Squamous Intraepithelial Lesion), SCC (Squamous Cell Carcinoma), AGC (Atypical Glandular Cells), or AIS; \*Exception: Participants with ASC-H or HSIL may be enrolled if histopathological evidence confirms no lesion or CIN1, upon investigator's assessment.\*.
• Pregnant or lactating women, or individuals planning to conceive during the study period.
• Participation in another clinical trial within 30 days before screening, or currently within the observational follow-up period of another clinical trial.
• Continuous systemic corticosteroid therapy (at a dose equivalent to >10 mg/day of prednisone) for more than one week within 30 days before screening; Exceptions: Hormone replacement therapy, and local administration (e.g., intra-tracheal, ocular).
• Continuous use of immunosuppressants (e.g., cyclosporine, tacrolimus, azathioprine, 6-mercaptopurine, antilymphocyte globulin) for more than one week within 30 days before screening.
• Administration of any non-live vaccine within 4 weeks, or any live vaccine within 4 weeks, before the first dose.
• History of receiving any therapeutic HPV vaccination; Note: Vaccination with approved prophylactic HPV vaccines is acceptable.
• Use of blood or blood-derived products (including immunoglobulins) within 3 months before the first dose, or planned use during the study period.
• History of immunodeficiency or autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis).
• Current or anticipated use during the study period of disease-modifying antirheumatic drugs (e.g., azathioprine, cyclophosphamide, cyclosporine, methotrexate) or biologic disease-modifying agents (e.g., infliximab, adalimumab, etanercept).
• History of solid organ or bone marrow transplantation.
• History or current diagnosis of other malignancies.
• Presence of active infection requiring systemic therapy (including active tuberculosis, active syphilis, and bacterial, fungal, or viral infections requiring systemic treatment).
• 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).
• Known history of allergy to any component of the investigational product or similar drugs; or history of severe allergy to any food, drug, or other substances (e.g., urticaria, eczema, dyspnea, angioedema).
• Severe dysfunction of other organs or severe cardiopulmonary disease.
• Presence of tattoos, scars, or active lesions/rashes within a 2 cm radius of the intended injection site (deltoid muscle) that may interfere with safety assessment.
• Known psychiatric disorders or substance abuse disorders that may interfere with the subject's ability to comply with study requirements.
• Any condition, therapy, laboratory abnormality, history of other circumstances, or current evidence that, in the investigator's judgment, may increase the risk associated with study participation or investigational product administration, may interfere with the interpretation of study results, or render the participant unsuitable for enrollment in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University First Hospital — Beijing

Identifiers

NCT: NCT07710703 · NWRD09-201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗