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

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)

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Cervical Intraepithelial Neoplasia Grade 2/3
• Intervention / Treatment: Combination product: Cevira®; Combination product: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 402
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Biopsy-confirmed HSIL histology determined by a panel of 3 pathologists from a central laboratory in each region (China, US, and Europe);

2. Adequate colposcopy including:

   1. visualization of entire cervical transformation zone including the squamocolumnar junction
   2. 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

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
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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cevira® treatment; The Cevira® treatment is an integrated combination of drug and device	Combination product: Cevira®; 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.
Placebo Comparator: Placebo ointment; 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; The placebo device is identical in appearance as the Cevira® device, but does not provide light.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Asieris MediTech (Hong Kong) Co., Ltd.
• Investigators: Principal Investigator: Jinghe Lang, MD,PhD, Peking Union Medical College Hospital; Study Chair: John Zhuang, PhD, Asieris MediTech (Hong Kong) Co., Ltd.

Publications and helpful links

General Publications

• Chen F, Novak Z, Dannecker C, Mokras C, Sui L, Zhang Y, You Z, Han L, Lang J, Hillemanns P. Multicentre, prospective, randomised controlled trial to evaluate hexaminolevulinate photodynamic therapy (Cevira) as a novel treatment in patients with high-grade squamous intraepithelial lesion: APRICITY phase 3 study protocol. BMJ Open. 2022 Jun 6;12(6):e061740. doi: 10.1136/bmjopen-2022-061740.

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2020
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: July 20, 2020
• First Submitted That Met QC Criteria: July 20, 2020
• First Posted (Actual): July 23, 2020

Study Record Updates

• Last Update Posted (Actual): August 12, 2022
• Last Update Submitted That Met QC Criteria: August 11, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Carcinoma in Situ; Cervical Intraepithelial Neoplasia
• Other Study ID Numbers: YHGT-CEV-R1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No