Efficacy and Safety of BG2109 in Chinese Subjects With Endometriosis

Study Overview
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Brief Summary
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The objective of this study is to demonstrate the efficacy and safety of BG2109 administered orally once daily at a dose of 100 mg alone or of 200 mg in combination with add-back hormone replacement therapy (ABT: estradiol (E2) 1 mg / norethisterone acetate (NETA) 0.5 mg) versus placebo, while under randomized treatment, in the management of moderate to severe endometriosis-associated pain (EAP) in chinese women with surgically confirmed endometriosis

Detailed Description
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This is a prospective, randomized, double-blind, placebo-controlled study to demonstrate the efficacy and safety of BG2109 administered orally once daily at doses of 100 mg alone and 200 mg in combination with low dose ABT (E2 1 mg/NETA 0.5 mg) versus placebo in the management of moderate to severe EAP in chinese women with surgically confirmed endometriosis. The entire study is divided into the core stage and the extension stage, with a total duration of approximately 72 weeks. This includes the prescreening wash-out period (if applicable), screening period (approximately 5-8 weeks), core stage (24 weeks) and extension stage (28 weeks), and the safety follow-up period (approximately 12 weeks)

Official Title
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A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Phase III Study to Evaluate the Efficacy and Safety of BG2109 in Chinese Subjects With Endometriosis

Conditions
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Endometriosis, Moderate to Severe Endometriosis-associated Pain

Intervention / Treatment
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* Drug: BG2109 100mg
* Drug: BG2109 200mg
* Drug: ABT(E2 1 mg / NETA 0.5 mg)
* Drug: BG2109 100mg Placebo
* Drug: BG2109 200mg Placebo
* Drug: ABT Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: The subject must be a premenopausal woman aged ≥18 years. The subject must have had her most recent surgical and histological diagnosis of pelvic endometriosis (laparoscopy, laparotomy, vaginal fornix or other biopsy) within 10 years and at least 2 months ago prior to screening. The subject has moderate to severe EAP during the screening period defined as: At the screening visit, a score of at least 2 for DYS and at least 2 for NMPP for the previous month assessed with the modified Biberoglu & Behrman (mB&B) scale Subject is confirmed to meet the following criteria during the screening period, within 35 consecutive calendar days prior to the baseline visit: i. Mean overall pelvic pain scores on the 0-10 NRS over the 5 days with the highest score ≥ 4; ii. At least two days with moderate or severe pain on the 0-3 VRS for pelvic pain over the days with uterine bleeding; iii. At least two days with moderate or severe pain on the 0-3 VRS for pelvic pain over the days without uterine bleeding; The subject has a Body Mass Index (BMI) ≥ 18 kg/m2 at the screening visit Key Exclusion Criteria: The subject is pregnant or breastfeeding, or plans to become pregnant during the study treatment period. The subject has a surgical history of: Hysterectomy, Bilateral oophorectomy, Surgeries that interfere with gastrointestinal motility, pH value, or absorption (including vagotomy, enterectomy, or gastric surgery), Any major abdominal surgery (including laparotomy for endometriosis) within 6 months or any interventional surgery for endometriosis (i.e. laparoscopy) performed within a period of 2 months before screening, or the subject is scheduled for a surgical abdominal procedure during the course of the study. The subject may need to take prohibited medications during the study or in the stipulated time before screening The subject has a contra-indication to ABT The subject has chronic pelvic pain that, in the opinion of the Investigator, is not caused by endometriosis and requires chronic analgesic or other chronic therapy which would interfere with the assessment of EAP The subject has conditions that affect bone mass density (BMD) assessment The subject did not respond to prior treatment with GnRH agonists or GnRH antagonists for endometriosis

Ages Eligible for Study
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Minimum Age: 18 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: BG2109 100 mg group<br> | Drug: BG2109 100mg<br>* One tablet of BG2109 100mg , oral , once daily<br>Drug: BG2109 200mg Placebo<br>* One tablet of BG2109 200mg Placebo, oral , once daily.<br>Drug: ABT Placebo<br>* One tablet of ABT Placebo, oral, once-daily<br>|
| Experimental: BG2109 200 mg +ABT group<br> | Drug: BG2109 200mg<br>* One tablet of BG2109 200mg, oral , once daily.<br>Drug: ABT(E2 1 mg / NETA 0.5 mg)<br>* One tablet of ABT(E2 1 mg / NETA 0.5 mg), oral, once-daily<br>Drug: BG2109 100mg Placebo<br>* One tablet of BG2109 100mg Placebo, oral , once daily.<br>|
| Placebo Comparator: Placebo group<br> | Drug: BG2109 100mg Placebo<br>* One tablet of BG2109 100mg Placebo, oral , once daily.<br>Drug: BG2109 200mg Placebo<br>* One tablet of BG2109 200mg Placebo, oral , once daily.<br>Drug: ABT Placebo<br>* One tablet of ABT Placebo, oral, once-daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dysmenorrhea (DYS) response rate at Week 12 | responders are defined as those with a significant decrease in mean DYS score measured using Numeric Rating Scale - NRS(0-10, higher scores mean worse) compared to baseline, with decreased or stable analgesic use for EAP | Week 12 | 
| Non-menstrual pelvic pain (NMPP) response rate at Week 12 | responders are defined as those with a significant decrease in mean NMPP score measured using Numeric Rating Scale - NRS(0-10, higher scores mean worse) compared to baseline, with decreased or stable analgesic use for EAP | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the interference of pain with the ability to perform daily activities from the baseline at week 24 | measured using the pain dimension in Endometriosis Health Profile-30 (EHP-30)(0-100, higher scores mean worse) | Week 24 | 
| Change of the mean overall pelvic pain(OPP) score from the baseline at week 24 | measured using Numeric Rating Scale - NRS(0-10, higher scores mean worse) | Week 24 | 
| Change of the mean DYS score from the baseline at week 24 | measured using Numeric Rating Scale - NRS(0-10, higher scores mean worse) | Week 24 | 
| Change of the mean NMPP score from the baseline at week 24 | measured using Numeric Rating Scale - NRS(0-10, higher scores mean worse) | Week 24 | 
| Ratio of subjects who do not use analgesics to treat EAP at week 24 |  | Week 24 |