NWRD09 mRNA vaccine for HPV16-related cervical HSIL

Safety, Tolerability and Immunogenicity Study of NWRD09 in HPV16 Related Cervical High-grade Squamous Intraepithelial Lesions (HSlL)

This Phase 1 study will try an mRNA vaccine called NWRD09 to see if it is safe and triggers immune responses in people with HPV16-related cervical HSIL.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years to 65 Years
• Sex: Female
• Sponsor: Newish Biotech (Wuxi) Co., Ltd. (industry)
• Drugs / interventions: infliximab, adalimumab, methotrexate, cyclophosphamide, prednisone
• Locations: 1 site (Beijing)
• Trial ID: NCT07047989 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label Phase 1 trial using a classical 3+3 dose-escalation design across three dose groups with 9–18 patients planned. Participants receive intramuscular NWRD09 at weeks 0, 2, 4 and 12, with safety follow-up until 28 days after the third administration. Colposcopy and biopsy are performed at week 24 to monitor lesion status, and 1–2 dose levels may be expanded after dose escalation to further evaluate safety, immunogenicity, and early efficacy. The study is sponsored by Newish Biotech and conducted at participating sites including Peking Union Medical College Hospital in Beijing.

Who should consider this trial

Good fit: Women aged 18–65 with HPV16-positive, histologically confirmed cervical HSIL, adequate colposcopic visualization of the lesion, and normal major organ function are the intended participants.

Not a fit: Patients with non-HPV16 lesions, pregnancy, significant organ dysfunction, immunosuppression, or inability to undergo required colposcopy/biopsy are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, NWRD09 could stimulate clearance of HPV16 and promote regression of HSIL, potentially reducing the need for surgical excision.

How similar studies have performed: Therapeutic HPV vaccines have produced mixed but promising results in prior trials with some lesion regression observed, and mRNA-based therapeutic vaccines are an emerging but still early-stage approach with limited encouraging data.

Eligibility criteria

Inclusion Criteria:

Patients had to meet all of the following inclusion criteria:

1. Women aged between 18 and 65 years.
2. HPV16-positive patients with histologically confirmed cervical HSlL.
3. Colposcopic examination should be adequate, enabling clear visualization of the entire squamocolumnar junction(SCJ), as well as the full extent of acetowhite staining or suspected cervical intraepithelial neoplasia (ClN) lesions, including the upper boundary of the lesion.
4. Major organ functions were normal within 1 week before the first NWRD09 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 ≥40mL/min (Cockcroft-Gault);
5. For premenopausal women of child bearing potential, a blood pregnancy test must yield a negative result within 7 days prior to the first administration of the investigational drug; eligible subjects with reproductive capacity, as well as their spouses/partners, must agree to use effective contraceptive measures during the trial period or for at least 6 month safter the end-of-study visit (Week 24).
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:

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

1. Any histologically confirmed adenocarcinoma or adenocarcinoma in situ (AIS) or invasive cancer.
2. Pregnant, breastfeeding, or planning to conceive during the study period.
3. Participated in another clinical trial or is in the observation period of another clinical trial within 30 days prior to screening.
4. Continuous (more than 1 week) use of corticosteroids (equivalent to \>10 mg/day of prednisone) within 30 days prior to screening, except for hormone replacement therapy and local administration such as inhaled or ocular treatments.
5. Continuous (more than 1 week) use of immunosuppressants (e.g., cyclosporine, tacrolimus, azathioprine, 6-mercaptopurine, and anti-lymphocyte globulin) within 30 days prior to screening.
6. Received any non-live/live vaccine injection within 4 weeks prior to the first dose of NWRD09.
7. Any history of therapeutic HPV vaccination (previously approved preventive HPV vaccination is acceptable).
8. Received treatment HSIL within 4 weeks prior to the first dose of NWRD09.
9. Prohibited: Use of blood/blood-derived products (e.g., immunoglobulins) within 3 months before first dose or intended use during the study.
10. History of immunodeficiency or autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis).
11. Current or anticipated use of disease-modifying antirheumatic drugs (e.g., azathioprine, cyclophosphamide, cyclosporine, methotrexate) and biological agents (e.g., infliximab, adalimumab, etanercept) during the study.
12. History of solid organ or bone marrow transplantation.
13. Past or current malignancies, except for adequately treated and completely cured ductal carcinoma in situ of the breast, basal cell carcinoma of the skin, superficial bladder tumors, or any other malignancies cured more than 5 years before entering the study.
14. Uncontrolled severe infections (\>Grade 2 NCI-CTCAE adverse events, version 5.0).
15. Patients who test positive for any of the following: hepatitis C virus (HCV)antibody, human immunodeficiency virus (HlV) antibody, or syphilis treponema antibody; except those with abnormal hepatitis B serology (i.e., positive for hepatitis B surface antigen \[HBsAg\] or hepatitis B core antibody \[HBcAb\]) but meet one of the following criteria:

1)HBV-DNA ≤2,500 copies/mL or ≤ 500lU/mL, or 2)HBV-DNA within the normal reference range of the testing center. 16.History of severe or multiple hypersensitivity to drugs or pharmaceutical preparations.

17.Severe dysfunction of other organs or heart and lung diseases. 18.History of definite neurological or psychiatric disorders, including epilepsy or dementia.

19.History of drug abuse or alcoholism. 20.Patients deemed unsuitable to participate in this clinical trial by the investigator.

Where this trial is running

Beijing

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

Study contacts

• Study coordinator: Yang Xiang

Conditions: High-grade Squamous Intraepithelial Lesion, NWRD09, mRNA vaccine, HPV16, HSIL