- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT07634497
HAL-PDT for Cervical Intraepithelial Neoplasia Grade 2
A Prospective, Multicenter Real-world Study of HAL-PDT for Cervical Intraepithelial Neoplasia Grade 2
Studieöversikt
Status
Betingelser
Detaljerad beskrivning
BACKGROUND:
Cervical intraepithelial neoplasia grade 2 (CIN2) is a high-grade precancerous lesion with a variable natural history. Current management options include active surveillance or local ablation/excision, but there is interest in minimally invasive treatments that preserve cervical integrity. Hexaminolevulinate photodynamic therapy (HAL-PDT) uses a photosensitizer that accumulates in dysplastic cells and, upon activation by red light, induces targeted cell death while potentially stimulating local anti-HPV immunity.
STUDY DESIGN RATIONALE:
This prospective, multicenter real-world study is designed to assess the effectiveness and safety of HAL-PDT in routine clinical practice. Unlike a traditional randomized controlled trial, this study uses an adaptive treatment regimen guided by colposcopic response at predefined time points. Participants receive an initial two PDT sessions, and additional sessions (up to a total of four) are given if lesions persist on colposcopy. This response-adaptive approach mirrors clinical decision-making and allows evaluation of a tailored treatment strategy.
DETAILED PROCEDURES:
- Index date: Day 1 (first PDT).
- PDT sessions: Day 1, Day 30-37 (mandatory for all). Additional PDT at Day 60-67 (if lesions present at D60 colposcopy) and/or at Day 90-97 (if lesions persist after third PDT).
- Colposcopy with biopsy for histopathology is performed at baseline (within 3 months pre-enrollment), at Month 6 (±7 days), and at Month 12 (±7 days). HPV genotyping and TCT are performed at screening, Month 3 (only for those receiving additional PDT), Month 6, and Month 12.
- Adverse events are collected from informed consent through the 12-month follow-up.
STATISTICAL METHODS:
The primary analysis will estimate the histopathological regression rate at 6 months with a two-sided 95% confidence interval using the exact binomial method. Secondary endpoints (regression at 12 months, HPV clearance at 6 and 12 months) will be analyzed similarly. Subgroup analyses by number of PDT sessions (2, 3, or 4) are exploratory. No formal hypothesis testing against an external control is planned. Safety data will be summarized descriptively.
SAMPLE SIZE CONSIDERATIONS:
A total of 500 participants will be enrolled.
Studietyp
Inskrivning (Beräknad)
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
- Vuxen
Tar emot friska volontärer
Testmetod
Studera befolkning
Beskrivning
Inclusion Criteria:
- Voluntarily participate in this clinical study, fully understand the study content, procedures, and potential adverse reactions, and be able to sign the written informed consent form.
- Able to complete the study in accordance with the study protocol.
- Female aged ≥18 years and ≤50 years.
Newly diagnosed High-Grade Squamous Intraepithelial Lesion (HSIL), cervical intraepithelial neoplasia grade 2 (CIN2) within 3 months, specifically: CIN2 confirmed by tissue biopsy within 3 months prior to the first treatment.
Note: Histopathological diagnosis will be assessed by the pathology department of the participating hospital for enrollment.
Adequate colposcopy, including:
- Complete visibility of the cervical transformation zone, including the squamocolumnar junction;
- Complete visibility of lesion margins;
- No lesion extension into the cervical canal.
- Cervical size deemed suitable for placement of the HAL-PDT device as assessed by the investigator according to the HAL-PDT package insert.
- Meets the following conditions: negative pregnancy test; no plan for pregnancy during the study period; no sexual activity or use of effective and reliable contraception from the end of the last menstrual period to the start of the study, and agreement to use condoms for barrier contraception during the study period.
Exclusion Criteria:
Subjects who meet any of the following criteria will be excluded from this study:
- Cervical adenocarcinoma in situ or other glandular lesions, invasive cervical cancer, or suspected malignant lesions.
- Lesions extending to the vaginal wall, cervical canal, or vaginal fornix, or lesions located on the vulva.
- Prior treatment (surgical or physical therapy) for the condition, or receipt of physical or surgical therapy within 3 months after the current histopathological diagnosis of CIN2.
- The date of the first HAL-PDT treatment falls within 7 half-lives of the last antiviral medication.
- History of toxic shock syndrome.
- Severe pelvic inflammatory disease, severe cervicitis, or other severe gynecological infectious diseases found on colposcopic or clinical examination.
- Investigator judges that vaginal bleeding during treatment may affect treatment outcomes.
- Receipt of any inactivated vaccine within 2 weeks prior to the first treatment, or any live vaccine within 4 weeks prior to the first treatment.
- Previous severe cardiovascular, cerebrovascular, neurological, psychiatric, endocrine, or hematopoietic disease that has not been cured; known severely compromised immune function, or need for long-term use of corticosteroids or immunosuppressants; history of malignancy within 5 years.
- History of clinically significant immunosuppression or confirmed autoimmune disease; or primary immunodeficiency.
- Known or newly identified active sexually transmitted diseases (STDs), including but not limited to HIV, syphilis, genital herpes, unless adequately treated and tested negative before study treatment.
- Presence of a cardiac pacemaker.
- Suspected or known porphyria, or known allergy to hexaminolevulinate, its chemically similar compounds, or photosensitizers.
- Allergy to silicone.
- Pregnant or breastfeeding women.
- Delivery or miscarriage within 6 weeks prior to enrollment.
- Participation in any other clinical trial within 30 days prior to HAL-PDT treatment.
- Poor compliance or judged by the investigator to be unsuitable for participation in this clinical study.
Studieplan
Hur är studien utformad?
Designdetaljer
Kohorter och interventioner
Grupp / Kohort |
|---|
|
HAL-PDT
All enrolled participants with histologically confirmed CIN2 receive response-guided HAL-PDT.
The first two PDT sessions are administered on Day 1 and Day 30-37.
At Day 60 (±7 days), colposcopy is performed: participants with complete lesion resolution receive no further PDT (Cohort A, 2 sessions total); those with persistent lesions receive a third PDT at Day 60-67, followed by colposcopy at Day 90.
If lesions resolve at Day 90, participants enter follow-up (Cohort B, 3 sessions total); if still persistent, a fourth PDT is given at Day 90-97 (Cohort C, 4 sessions total).
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Histopathological regression rate at 6 months
Tidsram: 6 months after the first HAL-PDT session
|
Proportion of participants with histopathological downgrading from cervical intraepithelial neoplasia grade 2 (CIN2) to normal or low-grade squamous intraepithelial lesion (LSIL/CIN1) on colposcopy-directed cervical biopsy, assessed at 6 months after the first HAL-PDT treatment.
|
6 months after the first HAL-PDT session
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Histopathological regression rate at 12 months
Tidsram: 12 months after the first HAL-PDT session
|
Proportion of participants with histopathological downgrading from cervical intraepithelial neoplasia grade 2 (CIN2) to normal or low-grade squamous intraepithelial lesion (LSIL/CIN1) on colposcopy-directed cervical biopsy, assessed at 12 months after the first HAL-PDT treatment.
|
12 months after the first HAL-PDT session
|
|
HPV clearance rate at 6 months
Tidsram: 6 months after the first HAL-PDT session
|
Proportion of participants with clearance of high-risk human papillomavirus (HPV) subtypes (including but not limited to HPV 16, 18, 52, 58) assessed at 6 months after the first HAL-PDT treatment.
HPV clearance is defined as undetectable of the same high-risk HPV subtype that was present at baseline.
|
6 months after the first HAL-PDT session
|
|
HPV clearance rate at 12 months
Tidsram: 12 months after the first HAL-PDT session
|
Proportion of participants with clearance of high-risk human papillomavirus (HPV) subtypes (including but not limited to HPV 16, 18, 52, 58) assessed at 12 months after the first HAL-PDT treatment.
HPV clearance is defined as undetectable of the same high-risk HPV subtype that was present at baseline.
|
12 months after the first HAL-PDT session
|
|
Safety and tolerability of HAL-PDT
Tidsram: From informed consent through 12 months after first HAL-PDT session (approximately up to 12 months)
|
Incidence, type, severity (mild, moderate, severe), duration, and relatedness to study treatment of adverse events (AEs) and serious adverse events (SAEs) occurring from signing of informed consent through the end of study follow-up.
|
From informed consent through 12 months after first HAL-PDT session (approximately up to 12 months)
|
Samarbetspartners och utredare
Studieavstämningsdatum
Studera stora datum
Studiestart (Beräknad)
Primärt slutförande (Beräknad)
Avslutad studie (Beräknad)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Faktisk)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Andra studie-ID-nummer
- WHRWS2601
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