Study of the Efficacy and Safety of Longidaze® for the Treatment of Patients With External Genital Endometriosis

Multicenter Prospective Non-interventional Study of the Efficacy and Safety of Longidaze®, Vaginal and Rectal Suppositories, 3000 IU, for the Treatment of Patients With External Genital Endometriosis

A study is being conducted to evaluate the efficacy and safety of Longidaze for the prevention and treatment of external genital endometriosis .

Study Overview

• Status: Active, not recruiting
• Conditions: External Genital Endometriosis
• Intervention / Treatment: Drug: Bovhyaluronidase azoximer

Detailed Description

The aim of the study is to compare the outcomes of complex therapy in patients with external genital endometriosis who, in addition to hormonal therapy, were prescribed Longidaze®, vaginal and rectal suppositories, 3000 IU, with the outcomes of therapy in patients who received only hormonal therapy.

• Study Type: Observational
• Enrollment (Anticipated): 149

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 109388
    • Federal State Autonomous Educational Institution of Higher Education "Peoples' Friendship University of Russia"
  • Moscow, Russian Federation, 119048
    • Federal State Autonomous Educational Institution of Higher Education First Moscow State Medical University named after I.M. Sechenov of the Ministry of Health of the Russian Federation
  • Chelyabinsk Region
    • Chelyabinsk, Chelyabinsk Region, Russian Federation, 454048
      • State budgetary healthcare institution "Chelyabinsk Regional Clinical Skin and Venereal Diseases Dispensary"
  • Leningrad Region
    • Saint Petersburg, Leningrad Region, Russian Federation, 199034
      • Federal State Budgetary Scientific Institution "Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott "
  • Nizhny Novgorod Region
    • Nizhny Novgorod, Nizhny Novgorod Region, Russian Federation, 603140
      • Private health care institution "Road clinical hospital at the station Nizhny Novgorod of the open joint stock company" Russian Railways "
  • Voronezh Region
    • Voronezh, Voronezh Region, Russian Federation, 394036
      • Federal State Budgetary Educational Institution of Higher Education "Voronezh State Medical University named after N.N. Burdenko "of the Ministry of Health of the Russian Federation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Patients with a verified diagnosis of external genital endometriosis, who, as part of routine clinical practice, were prescribed monotherapy with per os dienogest or combined treatment with a combination of dienogest + vaginal and rectal suppositories Longidaze®, 3000 ME (hereinafter referred to as Longidaze® )

Description

Inclusion Criteria:

1. Documented informed consent;
2. Patients over 18 years of age with active menstrual function;
3. Women with external genital endometriosis, confirmed morphologically and visually during laparoscopic or laparotomy surgery performed 10 years to 2 weeks prior to Day 0;

4. Patients in the framework of routine clinical practice in accordance with the instructions for use, prior to inclusion in the study, are assigned one of the following therapy regimens:

   • monotherapy with dienogest 2 mg daily for at least 6 months per os
   • complex treatment with dienogest 2 mg daily for at least 6 months per os in combination with vaginal and rectal suppositories Longidaze® 1 suppository 1 time every 2 days 10 suppositories, and then 1 suppository 1 time in 7 days 17 suppositories for another 120 days;
5. Willingness to use barrier methods of contraception.

Exclusion Criteria:

1. Women before menarche or after menopause
2. Adenomyosis;
3. Amenorrhea (more than 3 months in a row within 6 months before screening);
4. Patients who are scheduled to undergo surgery for endometriosis during the study;
5. Hormone therapy for endometriosis or the use of aromatase inhibitors within 16 weeks prior to Day 0;
6. Daily use of pain relievers for 7 consecutive days or more due to any other reason other than endometriosis;

6. Participation in clinical trials less than 30 days before the screening visit and / or 5 drug half-lives, whichever is longer.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Longidaze; 75 patients receiving combination therapy: Longidaze + dienogest	Drug: Bovhyaluronidase azoximer; Rectally or vaginally 1 suppository of Longidaze every 2 days. The main course of treatment - 10 suppositories (for 30 days). Then (according to the doctor's decision) supportive therapy is prescribed for 1 suppository 1 time in 7 days. Course of supportive treatment - 17 suppositories for another 120 days. The patients took dienogest according to the instructions for use.
Control; 74 patients receiving only Dienogest.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the severity of endometriosis-associated pelvic pain (Day 30)	Changes in the severity of endometriosis-associated pelvic pain by visual analogue scale (VAS) after 30 days from the baseline value in patients of the dienogest + Longidaze® combination therapy group compared with patients who received only dienogest. The Visual Analogue Scale (VAS) is designed to measure pain intensity. It is a continuous scale in the form of a horizontal line 10 cm (100 mm) long and located on it two extreme points: "no pain" and "the strongest pain you can imagine." The patient is asked to place a line perpendicularly crossing the visual analogue scale at the point that corresponds to his pain intensity. The ruler measures the distance (mm) between "no pain" and "the worst pain imaginable," providing a score range from 0 to 100. A higher score indicates more pain intensity.	Day 0, Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the severity of endometriosis-associated pelvic pain (Days 90, 150, 180)	Changes in the severity of endometriosis-associated pelvic pain according to the VAS after 90, 150 and 180 days relative to the baseline value in patients of the dienogest + Longidaze® combination therapy group compared with patients who received only dienogest. The Visual Analogue Scale (VAS) is designed to measure pain intensity. It is a continuous scale in the form of a horizontal line 10 cm (100 mm) long and located on it two extreme points: "no pain" and "the strongest pain you can imagine." The patient is asked to place a line perpendicularly crossing the visual analogue scale at the point that corresponds to his pain intensity. The ruler measures the distance (mm) between "no pain" and "the worst pain imaginable," providing a score range from 0 to 100. A higher score indicates more pain intensity.	Day 0, Day 90, Day 150, Day 180
Change in the Biberoglu and Berman scale	Change in the Biberoglu and Berman scale after 30, 90, 150 and 180 days from the baseline value from the start of treatment in patients of the dienogest + Longidaze® combination therapy group compared with patients who received only dienogest. The Biberoglu and Berman scale consists of five 4-point scales for assessing the severity of dysmenorrhea, dyspareunia and chronic pelvic pain not associated with menstruation, as well as the assessment of pain and static hyperalgesia during gynecological examination. In each of the scales, 0 points - no symptom, 3 points - the most pronounced symptom. The result is assessed by the sum of points for each symptom. With a sum of points from 1 to 2, pelvic pain is considered mild, from 3 to 5 - moderate, from 6 to 10 - strong, from 11 to 15 - severe.	Day 0, Day 30, Day 90, Day 150, Day 180
Change in the score on the SF-36 quality of life questionnaire	Change in the score on the SF-36 quality of life questionnaire after 30, 90, 150 and 180 days relative to the baseline value from the start of treatment in patients of the dienogest + Longidaze® combination therapy group compared with patients who received only dienogest.	Day 0, Day 30, Day 90, Day 150, Day 180
Change in the severity of uterine bleeding	Change in the severity of uterine bleeding after 30, 90, 150 and 180 days from the start of treatment in patients of the dienogest + Longidaze® combination therapy group compared with patients who received only dienogest. Patients will assess the severity of uterine bleeding in the patient's diary using the Mansfield-Voda-Jorgensen scale. There are five scoring options ranging from light bleeding to heavy bleeding. The rating is determined by the frequency of changing sanitary napkins or tampons, the degree of absorption of these products with blood, and also depends on the absorption properties of these products.	Day 0, Day 30, Day 90, Day 150, Day 180

Collaborators and Investigators

• Sponsor: NPO Petrovax

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2019
• Primary Completion (Actual): May 14, 2021
• Study Completion (Anticipated): August 1, 2021

Study Registration Dates

• First Submitted: July 5, 2021
• First Submitted That Met QC Criteria: July 5, 2021
• First Posted (Actual): July 15, 2021

Study Record Updates

• Last Update Posted (Actual): July 22, 2021
• Last Update Submitted That Met QC Criteria: July 15, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: longidaze; external genital endometriosis; bovhyaluronidase azoximer
• Additional Relevant MeSH Terms: Endometriosis
• Other Study ID Numbers: ISLAND

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