E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with cervical histologic HSIL.
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E.1.1.1 | Medical condition in easily understood language |
cervical histologic high-grade squamous intraepithelial lesions means that some changes have taken place to cervical epithelial |
cervikálna skvamózna intraepiteliálna lézia vysokého stupňa podľa histologickej klasifikácie znamená určité zmeny v bunkovej výstelke krčka maternice
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064455 |
E.1.2 | Term | HSIL |
E.1.2 | System Organ Class | 100000004872 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy and safety of Cevira® compared to placebo in treatment of patients with cervical histologic HSIL. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Biopsy-confirmed HSIL histology determined by a panel of three pathologists from at the central laboratory in of each region (China, US, and Europe), biopsy tests performed before the signing of the informed consent form within 2 months prior to administration are acceptable, no repeated test is required; 2. Adequate colposcopy including: a. visualization of entire cervical transformation zone including the squamocolumnar junction b. visualization of entire lesion margin 3. 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) 4. Average sized uterine cervix (approximately 27 mm diameter) suitable for application of the Cevira® device 5. Female (not breastfeeding, with negative pregnancy test and using either a highly effective method of contraception during the entire study and 30 days after end of the study or being post-menopausal for at least 1 year or sterilized women) 6. Age 18 or older (Note: Patients aged 18-20 should not be actively recruited) 7. Signed written informed consent
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E.4 | Principal exclusion criteria |
1. Biopsy-confirmed HSIL (CIN3) histology with a total lesion area covering more than half of the uterine cervix area 2. Invasive cervical cancer 3. Adenocarcinoma in situ, or other glandular intraepithelial lesions 4. Lesion(s) extending to the cervical canal (as clinically indicated and whether to perform endocervical curettage [ECC] test at the discretion of the investigators) 5. Lesion(s) extending to the vaginal vault 6. Current severe pelvic inflammatory disease, severe cervicitis, or other severe gynecological infection as per colposcopy and clinical examination 7. Vaginal bleeding at time of treatment at the discretion of the investigator 8. Pregnancy 9. Nursing 10. Childbirth or miscarriage within six weeks of enrolment 11. 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 12. History of toxic shock syndrome 13. Known or suspected porphyria 14. Known allergy to hexaminolevulinate or similar compounds (e.g. methyl aminolevulinate or aminolevulinic acid) 15. Known allergy to silicone. 16. Use of heart pacemaker, and other electronic implants 17. Use of any mechanical barriers such as the contraceptive FemCap 18. Inappropriate anatomical and physiological conditions (natural or acquired through disease) such as metrorrhagia and causes (myoma, endometrial carcinoma, polyposis, etc.), uterine/cervical prolapse, vaginal dryness, period of the woman's menstruation and other. If the therapeutic drugs for concomitant diseases have the effect of treating HPV, HSIL and tumours, as well as regulating immunologic function, which will affect the efficacy evaluation of Cevira® 19. Participation in other therapeutic clinical trials using investigational agents either concurrently or within the last 30 days or five half-lives of the drug, whichever is longer, prior to enrolment 20. Patients that in the investigator’s opinion are not suitable for participation 21. 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for IMP (Cevira® 5% HAL HC ointment): 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
The primary endpoint for IMD (Cevira® CL7 device): The performance of Cevira medical device is positively correlated with the efficacy of the Cevira ointment (Responder), as without the device's photodynamic therapy, components of Cevira ointment will not be absorbed and consequently will not provide the intended treatment effect. Therefore, the performance of Cevira device will be explained by the proportion of responders 6 months after treatment as defined for the primary endpoint for the IMP. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 months after first treatment |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints for IMP: The proportion of HPV positive patients with clearance of baseline HPV at 6 months after first treatment. The proportion of HPV16 positive patients with clearance of HPV16 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. The proportion of patients with histologic regression, defined as LSIL or normal histology, at 6 months after first treatment.
Secondary performance endpoints for IMD: The proportion of devices with correct light signals before insertion. The proportion of gynaecologists successfully insertinged the device within 15 minutes.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At 6 months after first treatment. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
China |
Poland |
Netherlands |
Romania |
Czechia |
Germany |
Hungary |
Russian Federation |
Slovakia |
Ukraine |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |