Evaluation of NWRD09 for HPV-16 Related Cervical HSIL

Official title

A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Study to Evaluate the Efficacy and Safety of NWRD09 in Patients With HPV16-Positive Cervical High-Grade Squamous Intraepithelial Lesion (HSIL)

Overview

This is a randomized, double-blind, placebo controlled Phase 2 study to determine the efficacy and safety of NWRD09 administered by intramuscular (IM) injection 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.

Detailed description

This is a Phase II, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of NWRD09 in patients with HPV16 positive cervical high-grade squamous intraepithelial lesion (HSIL). Eligible participants are randomized to receive either NWRD09 or the corresponding placebo.

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

Efficacy evaluations at Week 24 will include histopathological biopsy and HPV testing.

Interventions

• Biological NWRD09 Injection
  NWRD09 administered by intramuscular injection at weeks 0, 2, 4, and 12.
• Biological NWRD09 Placebo
  Placebo administered by intramuscular injection at weeks 0, 2, 4, and 12.

Primary outcome measures

• Proportion of Participants with Histopathological Regression of Cervical Lesions to non-HSIL (LSIL/CIN1 or no lesion) at week 24. [Time frame: Week24]

Secondary outcome measures (12)

• Incidence and severity of local and systemic adverse events (AEs). [Time frame: Up to week 64]
• Incidence and severity of all serious adverse events (SAEs). [Time frame: Up to week 64]
• Pregnancy occurrences and outcomes during the study period. [Time frame: Up to week 64]
• Incidence of investigational product-related adverse events (AEs) leading to treatment discontinuation. [Time frame: Up to week 64]
• Proportion of Participants with Histopathological Regression of Cervical Lesions to no lesions. [Time frame: Week 24]
• Proportion of Participants with Histopathological regression of Cervical Lesions to LSIL/CIN1. [Time frame: Week 24]
• Proportion of Participants with Virologically-proven Clearance of HPV 16. [Time frame: Week 24]
• Proportion of Participants with Histopathological Regression of Cervical Lesions to non-HSIL(LSIL /CIN1 or lesion) and with Virologically-proven Clearance of HPV 16. [Time frame: Week 24]
• Proportion of Participants with Histopathological Regression of Cervical Lesions to no Lesion and with Virologically-proven Clearance of HPV 16. [Time frame: Week 24]
• Proportion of Participants with Histopathological Regression to non-HSIL (LSIL/CIN1 or no lesion) in Participants with Baseline HPV16-only Infection. [Time frame: Week 24]
• Proportion of Participants with Histopathological Regression to no Lesion in Participants with Baseline HPV16-only Infection. [Time frame: Week 24]
• Proportion of Participants with Virologically-proven Clearance of Both HPV16 and non-HPV16 in Participants with Baseline Co-infection with non-HPV16. [Time frame: Week 24]

Eligibility criteria

Inclusion criteria

Participants had to meet all of the following inclusion criteria:

• Age between 18 and 65 years (inclusive), female;
• Confirmed by the central laboratory: histopathologically diagnosed cervical high-grade squamous intraepithelial lesion (HSIL) and HPV genotyping positive for HPV16;
• Colposcopy results at each study center during the screening period must meet the following criteria:

1\) The colposcopy examination is adequate, allowing clear visualization of the entire area of acetowhite epithelium or suspected cervical intraepithelial neoplasia (CIN) lesions, including the upper margin of the lesion; 2) If the upper margin of the lesion is not clearly visible, the endocervical curettage (ECC) result must be negative; 3) The area of cervical lesion is less than 75% of the cervical area visible by colposcopy; (4) Within 14 days (inclusive) before the first dose, major organ function meets the following criteria:

• Hematology: hemoglobin (Hb) ≥ 100 g/L; platelet count (PLT) ≥ 75 × 10⁹/L; absoluteneutrophil count ≥ 1.8 × 10⁹/L;
• 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;
• Kidney: serum creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance (Ccr) ≥ 40 mL/min (calculated by Cockcroft-Gault formula); (5) For premenopausal women with childbearing potential, serum pregnancy test within 14 days before the first dose must be negative. Eligible participants of childbearing potential and their spouse/partner must agree to use effective contraceptive measures during the study period or until 64 weeks after the first dose; (6) Fully understand the study and voluntarily sign the informed consent form (ICF), be able to communicate well with the investigator, and be able to complete all treatments, examinations, and visits as required by the study protocol.

Exclusion criteria

Participants with any of the following were excluded from the study:

• Any histopathologically confirmed cervical adenocarcinoma/adenocarcinoma in situ (AIS), vulvar, vaginal, or anal high-grade intraepithelial lesions, or invasive cancer;
• Women who are pregnant or breastfeeding, or who plan to become pregnant during the study period;
• Participation in another clinical trial within 30 days prior to screening, or currently being in the follow-up period of another clinical trial;
• Continuous use (for more than 1 week) of systemic glucocorticoid therapy (at a dose equivalent to >10 mg/day prednisone or equivalent dose of other glucocorticoids) or other immunosuppressive agents within 30 days prior to screening, except for the following:

• Inhaled, ophthalmic, or topical glucocorticoid therapy at a dose ≤10 mg/day prednisone or equivalent is permitted;
• Physiological glucocorticoid replacement therapy at a dose ≤10 mg/day prednisone or equivalent;
• Continuous use (for more than 1 week) of immunosuppressants such as cyclosporine, tacrolimus, azathioprine, 6-mercaptopurine, anti-lymphocyte globulin, etc., within 30 days prior to screening;
• Receipt 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;
• Any history of therapeutic HPV vaccination (approved prophylactic HPV vaccination is acceptable);
• Receipt of any drug or physical therapy for HSIL within 4 weeks prior to screening;
• Use of blood or blood-related products (including immunoglobulin) within 3 months prior to the first dose, or planned use during the study period;
• History of immunodeficiency or autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, etc.), or currently active autoimmune disease requiring systemic treatment (e.g., with disease-modifying agents, corticosteroids, or immunosuppressants);
• Current or anticipated continuous use (for more than 1 week) of disease-modifying antirheumatic drugs (e.g., azathioprine, cyclophosphamide, cyclosporine, methotrexate) and biologic disease-modifying antirheumatic drugs (e.g., infliximab, adalimumab, etanercept) during the study period;
• History of solid organ or bone marrow transplantation;
• Previous or current other malignancy;
• Uncontrolled serious infection (> Grade 2 NCI-CTCAE, version 6.0);
• Positive test for hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, or Treponema pallidum antibody; positive for hepatitis B surface antigen (HBsAg) unless HBV-DNA ≤ 2500 copies/mL or ≤ 500 IU/mL or within the normal range of the study site;
• Known allergy to any component of the investigational drug or similar drugs; history of severe allergic reactions to food, drugs, or other substances (e.g., urticaria, eczema, dyspnea, angioedema, etc.);
• Tattoos, scars, or active lesions/rash within 2 cm of the intended injection site (deltoid of the upper arm) that may affect safety observation;
• Severe dysfunction of other organs or cardiopulmonary disease;
• Definite history of neurological or psychiatric disorders, including epilepsy or dementia;
• History of drug abuse or alcohol use disorder;
• History or current evidence of any condition, treatment, laboratory abnormality, or other circumstances that may increase the risk of study participation or investigational product administration, or may interfere with interpretation of study results, and in the judgment of the investigator, make 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 · 15 centers

• Beijing Obstetrics and Gynecology Hospital, Capital Medical University — Beijing
• Cancer Hospital, Chinese Academy of Medical Sciences — Beijing
• Peking Union Medical College Hospital, Chinese Academy of Medical Sciences — Beijing
• Peking University First Hospital — Beijing
• Chongqing University Cancer Hospital — Chongqing
• The First Hospital Affiliated to AMU (SOUTHWEST HOSPITAL) — Chongqing
• Gansu Provincial Maternity and Child-care Hospital / Gansu Provincial central Hospital — Lanzhou
• Affiliated Hospital of Hebei University — Baoding
• … and 7 more centers

Identifiers

NCT: NCT07712692 · NWRD09-202

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗