A Study to Assess the Efficacy and Safety of OBE2109 in Subjects With Endometriosis

Endometriosis Clinical Trial

— EDELWEISS  

Official title:

A Randomized, Double-blind, Placebo-controlled, Phase 2b Dose-ranging Study to Assess the Efficacy and Safety of OBE2109 in Subjects With Endometriosis Associated Pain

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02778399
• Other study ID #: 15-OBE2109-001
• Status: Completed
• Phase: Phase 2
• Start date: July 2016
• Est. completion date: July 1, 2019

Study information

• Verified date: June 2022
• Source: ObsEva SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to assess the efficacy and safety of a range of oral doses of OBE2109 versus placebo, in reducing endometriosis associated pain.

Description:

The study is a prospective, dose-finding, randomized, parallel group, double-blind, placebo-controlled phase 2b study investigating the efficacy and safety of OBE2109 in the treatment of 330 women with moderate-to-severe endometriosis associated pain.

Subject will be randomized to one of 6 treatment groups in a 1:1:1:1:1:1 ratio (1 placebo group, 5 dose groups with different dosage/regimen).

Eligible subjects will be offered the opportunity to continue treatment with OBE2109 in an extension phase. Subjects who do not continue in the extension will enter the treatment-free follow-up phase of the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 328
• Est. completion date: July 1, 2019
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Key Inclusion Criteria:

• The subject must have had her most recent surgical and - if available - histological, diagnosis of pelvic endometriosis up to 10 years before screening.

• The subject has moderate to severe endometriosis-associated pain during the screening period.

• The subject has regular menstrual cycles.

• The subject has a BMI = 18 kg/m2 at the screening visit.

Key Exclusion Criteria:

• The subject is pregnant or breast feeding or is planning a pregnancy within the duration of the treatment period of the study.

• The subject had an interventional surgery for endometriosis performed within a period of 60 days before screening.

• The subject did not respond to prior treatment with gonadotropin releasing hormone (GnRH) agonists or GnRH antagonists for endometriosis.

• The subject has a history of, or known osteoporosis or other metabolic bone disease.

• The subject has chronic pelvic pain that is not caused by endometriosis and requires chronic analgesic / therapy, or that would interfere with the assessment of endometriosis related pain.

Related Conditions & MeSH terms

• Endometriosis

Intervention

Drug:
• Placebo
Placebo tablets for oral administration once daily
• OBE2109
OBE2109 tablets for oral administration once daily

Locations

Country	Name	City	State
Poland	Site reference ID 101	Katowice
Poland	Site reference ID 102	Katowice
Poland	Site reference ID 104	Lublin
Poland	Site reference ID 105	Lublin
Poland	Site reference ID 103	Szczecin
Russian Federation	Site reference ID 201	Moscow
Russian Federation	Site reference ID 202	Moscow
Russian Federation	Site reference ID 203	Moscow
Russian Federation	Site reference ID 204	Moscow
Russian Federation	Site reference ID 205	Saint Petersburg
Ukraine	Site reference ID 305	Ivano-Frankivs'k
Ukraine	Site reefrence ID 303	Kyiv
Ukraine	Site reference ID 301	Kyiv
Ukraine	Site reference ID 302	Kyiv
Ukraine	SIte reference ID 304	Kyiv
United States	Site reference ID 421	Albuquerque	New Mexico
United States	Site reference ID 430	Ann Arbor	Michigan
United States	Site reference ID 462	Arcadia	California
United States	Site reference ID 428	Atlanta	Georgia
United States	Site reference ID 459	Atlanta	Georgia
United States	Site reference ID 452	Austin	Texas
United States	Site reference ID 409	Bay City	Michigan
United States	Site reference ID 461	Beaumont	Texas
United States	Site reference ID 457	Boca Raton	Florida
United States	Site reference ID 408	Bristol	Tennessee
United States	Site reference ID 419	Bryn Mawr	Pennsylvania
United States	Site reference ID 467	Centreville	Virginia
United States	Site reference ID 455	Chandler	Arizona
United States	Site reference ID 403	Chattanooga	Tennessee
United States	Site reference ID 405	Chino	California
United States	Site reference ID 418	Clearwater	Florida
United States	Site reference ID 476	Columbia	South Carolina
United States	Site reference ID 447	Dallas	Texas
United States	Site reference ID 460	Dallas	Texas
United States	Site reference ID 443	Dayton	Ohio
United States	Site reference ID 474	Denver	Colorado
United States	Site reference ID 422	Draper	Utah
United States	Site reference ID 445	Fall River	Massachusetts
United States	Site reference ID 471	Fall River	Massachusetts
United States	Site reference ID 464	Fort Worth	Texas
United States	Site reference ID 472	Franklin	Ohio
United States	Site reference ID 437	Gainesville	Florida
United States	Site reference ID 478	Glen Burnie	Maryland
United States	Site reference ID 436	Greensboro	North Carolina
United States	Site reference ID 413	Houston	Texas
United States	Site reference ID 434	Houston	Texas
United States	Site reference ID 479	Houston	Texas
United States	Site reference ID 463	Huntington Park	California
United States	Site reference ID 449	Jenkintown	Pennsylvania
United States	Site reference ID 458	Jensen Beach	Florida
United States	Site reference ID 450	Lakewood	Colorado
United States	Site reference ID 425	Longmont	Colorado
United States	Site reference ID 454	Marrero	Louisiana
United States	Site reference ID 453	Metairie	Louisiana
United States	Site reference ID 411	Miami	Florida
United States	Site reference ID 424	Miami	Florida
United States	Site reference ID 435	Miami	Florida
United States	Site reference ID 420	Miami Lakes	Florida
United States	Site reference ID 441	Miami Springs	Florida
United States	Site reference ID 433	Morehead City	North Carolina
United States	Site reference ID 475	Nampa	Idaho
United States	Site reference ID 429	Nashville	Tennessee
United States	Site reference ID 423	New Port Richey	Florida
United States	Site reference ID 466	New York	New York
United States	Site reference ID 407	Norfolk	Virginia
United States	Site refenrec ID 469	Northridge	California
United States	Site reference ID 465	Oak Brook	Illinois
United States	Site reference ID 412	Richmond	Virginia
United States	Site reference ID 417	Richmond	Virginia
United States	Site reference ID 468	Saginaw	Michigan
United States	Site reference ID 473	Saginaw	Michigan
United States	Site reference ID 451	San Antonio	Texas
United States	Site reference ID 431	San Diego	California
United States	Site reference ID 402	Schertz	Texas
United States	Site reference ID 439	Scottsdale	Arizona
United States	Site reference ID 406	Seattle	Washington
United States	Site reference ID 404	Shawnee Mission	Kansas
United States	Site reference ID 427	Southfield	Michigan
United States	Site reference ID 426	Tampa	Florida
United States	Site reference ID 415	Tiffin	Ohio
United States	Site reference ID 440	Tustin	California
United States	Site reference ID 410	Washington	District of Columbia
United States	Site reference ID 432	Webster	Texas
United States	Site reference ID 442	Wellington	Florida
United States	Site reference ID 414	Westerville	Ohio
United States	Site reference ID 456	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
ObsEva SA

Countries where clinical trial is conducted

United States,  Poland,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects With 30% or Greater Reduction From Baseline to Week 12 in Mean Overall Pelvic Pain Score (0-3 VRS)	The primary efficacy endpoint of the study was a response at Week 12, with response defined as a reduction of 30% or greater from baseline in the mean overall pelvic pain score, defined as the mean of daily pain scores reported in electronic diary during the preceding 28 days (4-week period), assessed on a Verbal Rating Scale for pelvic pain of 0 (no pain) to 3 (severe pain). The baseline mean score was calculated as the mean of daily scores recorded in electronic diary over the two complete menstrual cycles performed during the screening period.; The relevant time points are Baseline and Week 12.	From baseline to week 12
Secondary	Change From Baseline to Week 12 in the Mean Overall Pelvic Pain Score (0-10 NRS)	This endpoint corresponds to the change from baseline to Week 12 in the mean overall pelvic pain score, defined as the mean of daily pain scores reported in electronic diary during the preceding 28 days (4-week period), assessed on a Numerical Rating Scale (NRS) for pelvic pain of 0 (no pelvic pain) to 10 (worst pelvic pain imaginable). The baseline mean score was calculated as the mean of daily scores recorded in electronic diary over the two complete menstrual cycles performed during the screening period.; The relevant time points are Baseline and Week 12.	From baseline to week 12
Secondary	Percentage of Subjects With 30% or Greater Reduction From Baseline to Week 12 in Mean Pelvic Pain Scores (0-3 VRS) for Days With Uterine Bleeding	This endpoint corresponds to a response at Week 12, with response defined as a reduction of 30% or greater from baseline in the mean pelvic pain score for days with uterine bleeding/spotting, defined as the mean of daily pain scores on days with uterine bleeding/spotting recorded in electronic diary during the preceding 28 days (4-week period), assessed on a Verbal Rating Scale for pelvic pain of 0 (no pain) to 3 (severe pain). The baseline mean score was calculated as the mean of daily scores recorded in electronic diary over the two complete menstrual cycles performed during the screening period.; The relevant time points are Baseline and Week 12.	From baseline to week 12
Secondary	Percentage of Subjects With 30% or Greater Reduction From Baseline to Week 12 in Mean Pelvic Pain Scores (0-3 VRS) for Days With no Uterine Bleeding	This endpoint corresponds to a response at Week 12, with response defined as a reduction of 30% or greater from baseline in the mean pelvic pain score for days with no uterine bleeding, defined as the mean of daily pain scores on days with no uterine bleeding recorded in electronic diary during the preceding 28 days (4-week period) on a Verbal Rating Scale for pelvic pain of 0 (no pain) to 3 (severe pain). The baseline mean score was calculated as the mean of daily scores recorded in electronic diary over the two complete menstrual cycles performed during the screening period.; The relevant time points are Baseline and Week 12.	From baseline to week 12
Secondary	Change From Baseline to Week 12 in the Mean Dyspareunia Score (0-3 VRS)	This endpoint corresponds to the change from baseline to Week 12 in the mean dyspareunia score, defined as the mean of daily dyspareunia scores recorded in electronic diary during the preceding 28 days (4-week period), assessed on a 0-3 Verbal Rating Scale (VRS) for dyspareunia, with 0 representing "No discomfort during sexual intercourse" and 3 representing "I avoided sexual intercourse because of pain". The baseline mean score was calculated as the mean of daily scores recorded in electronic diary over the two complete menstrual cycles performed during the screening period.; The dyspareunia questionnaire also included an option "not applicable: I was not sexually active for reasons other than my endometriosis or did not have sexual intercourse"; for scoring, answering "not applicable" was considered like a missing value.; The relevant time points are Baseline and Week 12.	From baseline to week 12
Secondary	Change From Baseline to Week 12 in the Mean Dyschezia Score (0-10 NRS)	This endpoint corresponds to the change from baseline to week 12 in the mean dyschezia score, defined as the mean of weekly dyschezia scores reported in electronic diary during the preceding 28 days (4-week period), assessed on a 0-10 Numerical Rating Scale for dyschezia, with 0 representing no pain and 10 representing the worst pain imaginable. The baseline mean score was calculated as the mean of weekly scores recorded in electronic diary over the two complete menstrual cycles performed during the screening period.; The relevant time points are Baseline and Week 12.	From baseline to week 12
Secondary	Percentage of Subjects With Any Analgesics Use at Week 12	This endpoint corresponds to the percentage of subjects at week 12 who recorded at least one pain medication intake in electronic diary during the preceding 28 days (4-week period).	Up to week 12
Secondary	Change From Baseline to Week 12 in the Mean Score of Endometriosis Health Profile-30 (EHP-30) Pain Domain	This endpoint corresponds to the change from baseline to Week 12 in the mean score of pain dimension of the EHP-30. The EHP-30 questionnaire was answered on electronic diary after activation by site staff during subject's monthly visits at site.; The EHP-30 pain dimension consists of 11 items each addressing the effect of pain on various activities in the past 4 weeks and each assessed on a 5-point scale (0=Never through to 4=Always). Scaled score was equalled to total of raw score of each item in scale divided by the maximum possible raw score of all the items in the dimension, multiplied by 100, resulting in a score on a scale from 0 (best possible health status) to 100 (worst possible health status).; The relevant time points are Baseline and Week 12.	From baseline to week 12
Secondary	Percentage of Subjects With Improvement in the Patient Global Impression of Change (PGIC) Score at Week 12	The PGIC questionnaire consists of one question rated on a seven point scale (1="Very Much Improved" to 7="Very Much Worse"), with which the subject had to qualify her overall status since the start of the study. The PGIC was answered on electronic diary after activation by site staff during Week 12 visit at site.; This endpoint corresponds to the percentage of subjects with an "improvement" in the PGIC score, which includes all subjects who answered "Very much improved" or "Much improved" or "Minimally improved" at Week 12.	Up to week 12
Secondary	Percentage of Subjects With an Endometriosis Severity Score of "Severe" at Week 12	Subject was asked monthly on electronic diary to assess their impression of endometriosis severity, considering the preceding 4-weeks, with following possible answers: no symptoms, very mild, mild, moderate, severe. This question was programmed to raise automatically every 4 weeks on the subject electronic diary. Result reported here is the percentage of subjects who answered "severe" at week 12.	Up to week 12
Secondary	Change From Baseline to Week 12 in the Difficulty in Doing Daily Activities Mean Score	This endpoint corresponds to the change from baseline to Week 12 in the mean of daily scores for "difficulty in doing daily activities", assessed via electronic diary during the preceding 28 days (4-week period), on a Numerical Rating Scale (NRS) of 0 (no difficulty doing daily activities) to 10 (unable to do daily activities). The baseline mean score was calculated as the mean of daily scores recorded in electronic diary over the two complete menstrual cycles performed during the screening period.; The relevant time points are Baseline and Week 12.	From baseline to week 12
Secondary	Percentage Change From Baseline to Week 24 in Bone Mineral Density (BMD)	Change from baseline to Week 24 in BMD assessed by dual-energy X-ray absorptiometry (DXA) scan of LUMBAR SPINE.	From baseline up to week 24
Secondary	Number of Non Benign Endometrial Biopsies at Week 24	Any pathological changes in the endometrium at week 24 were assessed from endometrial biopsies. The number of non benign biopsies at Week 24 is presented per treatment arm.; Note: an isolated case of hyperplasia (without atypia) was observed at week 12 in the 200 mg group in a subject whose screening biopsy results were normal. A follow-up biopsy at week 24 revealed no abnormalities.	Week 24
Secondary	Change From Baseline to Week 24 in Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS)	The endometrium thickness was measured by TVUS at screening and at Week 24 visit by the gynaecologist and result was recorded in mm. This endpoint reports the changes from baseline to Week 24 in the endometrial thickness.	From baseline up to week 24
Secondary	Percentage Change From Baseline to Week 24 in the Clinical Laboratory Assessments: LDL	This endpoint reports the change from baseline up to Week 24 in the clinical laboratory assessments: LDL cholesterol.	From baseline up to week 24
Secondary	Percentage Change From Baseline to Week 24 in Clinical Laboratory Assessments: HDL	This endpoint reports the change from baseline to week 24 in clinical laboratory assessments: HDL cholesterol.	From Baseline up to week 24
Secondary	Percentage Change From Baseline to Week 24 in Clinical Laboratory Assessments: Triglycerides	This endpoint reports the change from baseline to week 24 in clinical laboratory assessments: triglycerides.	From baseline up to week 24