E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with cervical histologic HSIL.
|
|
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 |
|
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 |
|
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. |
|
E.2.2 | Secondary objectives of the trial |
|
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); 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 suitable for application of the Cevira® device 5. Use of adequate birth control until completion of the 6 month assessment visit 6. Age 18 or older (Note: Patients aged 18-20 should not be actively recruited) 7. Signed written informed consent
|
|
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. Previous treatment of cervical intraepithelial lesions (CIN) or cervical invasive disease 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 17. Participation in other therapeutic clinical trials using investigational agents either concurrently or within the last 30 days 18. Patients that in the investigator’s opinion are not suitable for participation 19. 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 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
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
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 months after first treatment |
|
E.5.2 | Secondary end point(s) |
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.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At 6 months after first treatment. |
|
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 |
Germany |
Hungary |
Romania |
Russian Federation |
Ukraine |
|
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
|
Patients in the placebo treatment group visit 7 is the last study visit. Patients in the active treatment group should continue in the study extension (Visit E1). |
|
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 | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
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 |