Efficacy and Safety of Cevira® in Patients With Cervical Histologic High-grade Squamous Intraepithelial Lesions (HSIL)

Study Overview
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Brief Summary
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A double blind, prospective, randomized, placebo controlled, multi-center phase 3 study to evaluate efficacy and safety of Cevira® in patients with cervical histologic high-grade squamous intraepithelial lesions (HSIL).

Detailed Description
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To evaluate the efficacy and safety of Cevira® compared to placebo in treatment of patients with cervical histologic HSIL.A total of 384 subjects will be enrolled globally, among which, 300 subjects of them will be enrolled in China.

Official Title
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A Double Blind, Prospective, Randomized, Placebo Controlled, Multi-center Phase 3 Study to Evaluate Efficacy and Safety of Cevira® in Patients With Cervical Histologic High-grade Squamous Intraepithelial Lesions (HSIL)

Conditions
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Cervical Intraepithelial Neoplasia Grade 2/3

Intervention / Treatment
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* Combination Product: Cevira®
* Combination Product: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy-confirmed HSIL histology determined by a panel of 3 pathologists from a central laboratory in each region (China, US, and Europe); Adequate colposcopy including: visualization of entire cervical transformation zone including the squamocolumnar junction visualization of entire lesion margin Colposcopically visible lesion after biopsy, before treatment (Note: To ensure a colposcopically visible lesion after biopsy, the lesion should cover approximately 15% of the uterine cervix before biopsy) Average sized uterine cervix suitable for application of the Cevira® device Use of adequate birth control until completion of the 6 month assessment visit Age 18 or older (Note: Patients aged 18-20 should not be actively recruited) Signed written informed consent Exclusion Criteria: Biopsy-confirmed HSIL (CIN3) histology with a total lesion area covering more than half of the uterine cervix area Invasive cervical cancer Adenocarcinoma in situ, or other glandular intraepithelial lesions Lesion(s) extending to the cervical canal (as clinically indicated and whether to perform endocervical curettage [ECC] test at the discretion of the investigators) Lesion(s) extending to the vaginal vault Current severe pelvic inflammatory disease, severe cervicitis, or other severe gynecological infection as per colposcopy and clinical examination Vaginal bleeding at time of treatment at the discretion of the investigator Pregnancy Nursing Childbirth or miscarriage within six weeks of enrolment Patients who previously received surgical treatment, have incomplete cervical structure and have recurrent HSIL; or patients who received other treatment after the confirmed diagnosis of HSIL History of toxic shock syndrome Known or suspected porphyria Known allergy to hexaminolevulinate or similar compounds (e.g. methyl aminolevulinate or aminolevulinic acid) Known allergy to silicone Use of heart pacemaker Participation in other therapeutic clinical trials using investigational agents either concurrently or within the last 30 days Patients that in the investigator's opinion are not suitable for participation Patient is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cevira® treatment<br>The Cevira® treatment is an integrated combination of drug and device | Combination Product: Cevira®<br>* The device is a single-use, disposable, LED-based red light source. The device will automatically switch on the light 5 hours after administration, and provide continuous photoactivation of 125 J/cm2 over 4.6 hours before automatically shutting down.<br>|
| Placebo Comparator: Placebo ointment<br>The placebo ointment contains only vehicle, and is similar in appearance and consistence as the Cevira® ointment. The placebo device is identical in appearance as the Cevira® device, but does not provide light. | Combination Product: Placebo<br>* The placebo device is identical in appearance as the Cevira® device, but does not provide light.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of responders at 6 months after first treatment | A responder is defined as follows: Normal histology; or LSIL histology and clearance of baseline HPV | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of HPV positive patients with clearance of baseline HPV at 6 months after first treatment. | The proportion of HPV positive patients with clearance of baseline HPV at 6 months after first treatment. | 6 months | 
| The proportion of HPV16 positive patients with clearance of HPV16 at 6 months after first treatment. | The proportion of HPV16 positive patients with clearance of HPV16 at 6 months after first treatment. | 6 months | 
| The proportion of HPV16 and/or HPV18 positive patients with clearance of baseline HPV at 6 months after first treatment. | The proportion of HPV16 and/or HPV18 positive patients with clearance of baseline HPV at 6 months after first treatment. | 6 months | 
| The proportion of patients with histologic regression, defined as LSIL or normal histology, at 6 months after first treatment. | The proportion of patients with histologic regression, defined as LSIL or normal histology, at 6 months after first treatment. | 6 months |