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

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.

Time frame: From baseline to week 12

Population: Number of subjects with available score in the respective group, from the Full Analysis Set (All randomized subjects who received at least one dose of study drug and had at least one assessment after first dose).~Data for the 75mg group (FD) and 75mg titrated group (TD) were combined for the analyses of the first 12 weeks of treatment, as pre-specified in the protocol (section 9.5).

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.

Time frame: From baseline to week 12

Population: Number of subjects with available score in the respective group, from the Full Analysis Set (All randomized subjects who received at least one dose of study drug and had at least one assessment after first dose).~Data for the 75mg group (FD) and 75mg titrated group (TD) were combined for the analyses of the first 12 weeks of treatment, as pre-specified in the protocol (section 9.5).

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.

Time frame: From baseline to week 12

Population: Number of subjects with available score in the respective group, from the Full Analysis Set (All randomized subjects who received at least one dose of study drug and had at least one assessment after first dose).~Data for the 75mg group (FD) and 75mg titrated group (TD) were combined for the analyses of the first 12 weeks of treatment, as pre-specified in the protocol (section 9.5).

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.

Time frame: From baseline to week 12

Population: Number of subjects with available score in the respective group, from the Full Analysis Set (All randomized subjects who received at least one dose of study drug and had at least one assessment after first dose).~Data for the 75mg group (FD) and 75mg titrated group (TD) were combined for the analyses of the first 12 weeks of treatment, as pre-specified in the protocol (section 9.5).

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.

Time frame: From baseline to week 12

Population: Number of subjects with available score in the respective group, from the Full Analysis Set (All randomized subjects who received at least one dose of study drug and had at least one assessment after first dose).~Data for the 75mg group (FD) and 75mg titrated group (TD) were combined for the analyses of the first 12 weeks of treatment, as pre-specified in the protocol (section 9.5).

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.

Time frame: From baseline to week 12

Population: Number of subjects with available score in the respective group, from the Full Analysis Set (All randomized subjects who received at least one dose of study drug and had at least one assessment after first dose).~Data for the 75mg group (FD) and 75mg titrated group (TD) were combined for the analyses of the first 12 weeks of treatment, as pre-specified in the protocol (section 9.5).

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.

Time frame: From baseline up to week 24

Population: Number of subjects with available TVUS result at Week 24 in the respective group, from the Safety Set (all randomized subjects who received at least one dose of double-blind study drug irrespective of the treatment received).

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.

Time frame: Week 24

Population: Number of subjects with available endometrial biopsy result at Week 24 in the respective group (excluding those with tissue unsatisfactory for evaluation), from the Safety Set (all randomized subjects who received at least one dose of double-blind study drug irrespective of the treatment received).

Change from baseline to Week 24 in BMD assessed by dual-energy X-ray absorptiometry (DXA) scan of LUMBAR SPINE.

Time frame: From baseline up to week 24

Population: Number of subjects with available BMD results at Week 24 in the respective group, from the Safety Set (all randomized subjects who received at least one dose of double-blind study drug irrespective of the treatment received).

This endpoint reports the change from baseline to week 24 in clinical laboratory assessments: HDL cholesterol.

Time frame: From Baseline up to week 24

Population: Number of subjects with available laboratory HDL result at Week 24 in the respective group, from the Safety Set (all randomized subjects who received at least one dose of double-blind study drug irrespective of the treatment received).

This endpoint reports the change from baseline to week 24 in clinical laboratory assessments: triglycerides.

Time frame: From baseline up to week 24

Population: Number of subjects with available laboratory result for Triglycerides at Week 24 in the respective group, from the Safety Set (all randomized subjects who received at least one dose of double-blind study drug irrespective of the treatment received).

This endpoint reports the change from baseline up to Week 24 in the clinical laboratory assessments: LDL cholesterol.

Time frame: From baseline up to week 24

Population: Number of subjects with available laboratory LDL result at Week 24 in the respective group, from the Safety Set (all randomized subjects who received at least one dose of double-blind study drug irrespective of the treatment received).

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.

Time frame: From baseline to week 12

Population: Number of subjects with available score in the respective group, from the Full Analysis Set (All randomized subjects who received at least one dose of study drug and had at least one assessment after first dose).~Data for the 75mg group (FD) and 75mg titrated group (TD) were combined for the analyses of the first 12 weeks of treatment, as pre-specified in the protocol (section 9.5).

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.

Time frame: From baseline to week 12

Population: Number of subjects with available score in the respective group, from the Full Analysis Set (All randomized subjects who received at least one dose of study drug and had at least one assessment after first dose).~Data for the 75mg group (FD) and 75mg titrated group (TD) were combined for the analyses of the first 12 weeks of treatment, as pre-specified in the protocol (section 9.5).

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.

Time frame: Up to week 12

Population: Number of subjects with available score in the respective group, from the Full Analysis Set (All randomized subjects who received at least one dose of study drug and had at least one assessment after first dose).~Data for the 75mg group (FD) and 75mg titrated group (TD) were combined for the analyses of the first 12 weeks of treatment, as pre-specified in the protocol (section 9.5).

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).

Time frame: Up to week 12

Population: Number of subjects with available score in the respective group, from the Full Analysis Set (All randomized subjects who received at least one dose of study drug and had at least one assessment after first dose).~Data for the 75mg group (FD) and 75mg titrated group (TD) were combined for the analyses of the first 12 weeks of treatment, as pre-specified in the protocol (section 9.5).

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.

Time frame: Up to week 12

Population: Number of subjects with available score in the respective group, from the Full Analysis Set (All randomized subjects who received at least one dose of study drug and had at least one assessment after first dose).~Data for the 75mg group (FD) and 75mg titrated group (TD) were combined for the analyses of the first 12 weeks of treatment, as pre-specified in the protocol (section 9.5).