Persistent HPV16 Infection
Conditions
Keywords
persistent HPV16 infection, therapeutic mRNA vaccine, NWRD09
Brief summary
This is an open-label, single-center, investigator-initiated exploratory trial evaluating NWRD09 in 10 participants with persistent HPV16 infection in the anal region.
Detailed description
This is an open-label, single-center, investigator-initiated clinical trial (IIT) designed to evaluate the efficacy, safety, and immunogenicity of NWRD09 in patients with persistent HPV16 infection localized to the anal region. A total of 10 participants will be enrolled and allocated to two parallel treatment groups. Participants are assigned to two parallel treatment groups, with one sentinel participant per group. Sentinel safety observation over 7 days post-first dose precedes enrollment of subsequent participants. Objectives include assessment of safety/tolerability, HPV16 DNA clearance, cytological regression, histopathological improvement (for baseline AIN1), and cellular immune responses through Week 28.
Interventions
DRUGNWRD09
Each participant will be administered NWRD09 by IM injection
Sponsors
Newish Biotech (Wuxi) Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Female and male, aged 18 to 60 years (inclusive). 2. HPV DNA genotyping of anal specimens demonstrates positivity for HPV16, with documented persistence for at least 12 months (≥12 months). 3. Histopathological findings show low-grade lesion, inflammation, or no abnormality. 4. Adequate organ function within 4 week before the first dose. 5. For premenopausal women of childbearing potential: a negative serum pregnancy test within 4 weeks 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. 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. Key
Exclusion criteria
1. Any histopathologically confirmed adenocarcinoma/adenocarcinoma in situ (AIS), high-grade cervical, vulvar, vaginal, or anal intraepithelial neoplasia, or invasive cancer. 2. Pregnant or breastfeeding women, or those planning to become pregnant during the study period. 3. Participation in another clinical trial within 30 days prior to screening, or currently being in the follow-up period of another clinical trial. 4. Continuous use (for \>1 week) of systemic corticosteroids at a dose equivalent to \>10 mg/day of prednisone within 30 days prior to screening, with the exception of hormone replacement therapy and topical administration (e.g., intratracheal, ophthalmic). 5. Continuous use (for \>1 week) of immunosuppressants (e.g., cyclosporine, tacrolimus, azathioprine, 6-mercaptopurine, antilymphocyte globulin) within 30 days prior to screening. 6. Receipt of any inactivated or live vaccine within 4 weeks prior to the first dose of study drug. 7. Receipt of any AIN-related drug or physical therapy within 4 weeks prior to the first dose. 8. History of any therapeutic HPV vaccination (prior receipt of licensed prophylactic HPV vaccines is acceptable). 9. Use of blood or blood-related products (including immunoglobulins) within 3 months prior to the first dose, or planned use during the study period. 10. History of immunodeficiency or autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, etc.).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of local and systemic adverse events (AEs). | Up to 28 weeks | Based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V6.0, adverse events (AEs) and serious adverse events (SAEs) will be monitored. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with virologically-proven clearance of HPV 16 at week 16. | Week 16 | The number of participants with virologically-proven clearance of HPV 16 at week 16. |
| Proportion of participants with virologically-proven clearance of HPV 16 at week 28. | Week 28 | The number of participants with virologically-proven clearance of HPV 16 at week 28. |
| Proportion of participants with virologically-proven clearance of HPV 16 at weeks 16 and 28. | Weeks 16、28 | The number of participants with virologically-proven clearance of HPV 16 at weeks 16 and 28. |
| Proportion of participants with baseline AIN1 showing histopathological regression to no lesions at 28 weeks after the first dose. | Week 28 | The number of participants with AIN1 showing histopathological regression to no lesions at week 28. |
| Levels of cellular immune responses. | Weeks 6, 16 , 28 | Levels of cellular immune responses measured by interferon-gamma enzyme-linked immunospot (IFN-γ ELISPOT) assay in peripheral blood mononuclear cells (PBMCs) of participants at baseline and at weeks 6, 16, 28. |
Countries
China
Contacts
CONTACTDr. Chen Zeyang, MD
PRINCIPAL_INVESTIGATORPengyuan Wang, MD
Peking University First Hospital
PRINCIPAL_INVESTIGATORZeyang Chen, MD
Peking University First Hospital
Outcome results
None listed