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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Endometriosis

Intervention / Treatment
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* Drug: Placebo
* Drug: OBE2109


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OBE2109 50 mg<br> | Drug: OBE2109<br>* OBE2109 tablets for oral administration once daily<br>|
| Experimental: OBE2109 75mg fixed dose (FD)<br> | Drug: OBE2109<br>* OBE2109 tablets for oral administration once daily<br>|
| Experimental: OBE2109 75mg titrated dose (TD)<br> | Drug: OBE2109<br>* OBE2109 tablets for oral administration once daily<br>|
| Experimental: OBE2109 100mg<br> | Drug: OBE2109<br>* OBE2109 tablets for oral administration once daily<br>|
| Experimental: OBE2109 200 mg<br> | Drug: OBE2109<br>* OBE2109 tablets for oral administration once daily<br>|
| Placebo Comparator: Placebo / OBE2109 100mg<br>Participants received placebo for the first 12 weeks and were then crossed-over to active treatment with OBE2109 100mg for a further 12 weeks. | Drug: Placebo<br>* Placebo tablets for oral administration once daily<br>Drug: OBE2109<br>* OBE2109 tablets for oral administration once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pelvic Pain, Endometriosis, Dysmenorrhea, Dyspareunia