Efficacy and Safety of OBE2109 in Subjects With Heavy Menstrual Bleeding Associated With Uterine Fibroids

Study Overview
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Brief Summary
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The primary objective of this study is to demonstrate the superior efficacy versus placebo of OBE2109 alone and in combination with add-back therapy for the reduction of heavy menstrual bleeding associated with uterine fibroids in premenopausal women.

Detailed Description
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The study is a prospective, randomized, parallel group, double-blind, placebo-controlled phase 3 study investigating the efficacy and safety of OBE2109 alone and in combination with add-back therapy for the treatment of uterine fibroids. Subjects will be randomized to one of 5 treatment groups in a 1:1:1:1:1 ratio.

Official Title
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A Phase 3, Multicentre, Randomized, Double-blind, Placebo-controlled Study Investigating the Efficacy and Safety of Daily Oral Administration of OBE2109 Alone and in Combination With Add-back Therapy for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women

Conditions
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Uterine Fibroids, Heavy Menstrual Bleeding

Intervention / Treatment
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* Drug: OBE2109
* Drug: Placebo to match OBE2109
* Drug: Placebo to match Add-back
* Drug: Add-back


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Premenopausal woman at screening. Body Mass Index ≥ 18 kg/m2. Menstrual cycles ≥ 21 days and ≤ 40 days. Presence of uterine fibroids. Heavy menstrual blood loss for each of the 2 menstrual periods assessed at screening using the alkaline hematin method. 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. History of uterus surgery that would interfere with the study. The subject's condition is so severe that she will require surgery within 6 months regardless of the treatment provided. Undiagnosed abnormal uterine bleeding. Significant risk of osteoporosis or history of, or known osteoporosis or other metabolic bone disease.

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: OBE2109 dose 1 (100mg) + Placebo Add-back<br> | Drug: OBE2109<br>* OBE2109 100mg tablets for oral administration once daily<br>Drug: Placebo to match OBE2109<br>* Placebo to match OBE2109 100mg tablets for oral administration once daily<br>Drug: Placebo to match Add-back<br>* Placebo to match Add-back (E2 1 mg / NETA 0.5 mg) for oral administration once daily<br>|
| Experimental: OBE2109 dose 1 (100mg) + Add-back<br> | Drug: OBE2109<br>* OBE2109 100mg tablets for oral administration once daily<br>Drug: Placebo to match OBE2109<br>* Placebo to match OBE2109 100mg tablets for oral administration once daily<br>Drug: Add-back<br>* Add-back (E2 1 mg / NETA 0.5 mg) for oral administration once daily<br>|
| Experimental: OBE2109 dose 2 (200mg) + Placebo Add-back / OBE2109 dose 2 (200 mg) + Add-back<br> | Drug: OBE2109<br>* OBE2109 100mg tablets for oral administration once daily<br>Drug: Placebo to match Add-back<br>* Placebo to match Add-back (E2 1 mg / NETA 0.5 mg) for oral administration once daily<br>Drug: Add-back<br>* Add-back (E2 1 mg / NETA 0.5 mg) for oral administration once daily<br>|
| Experimental: OBE2109 dose 2 (200mg) + Add-back<br> | Drug: OBE2109<br>* OBE2109 100mg tablets for oral administration once daily<br>Drug: Add-back<br>* Add-back (E2 1 mg / NETA 0.5 mg) for oral administration once daily<br>|
| Placebo Comparator: Placebo + Placebo Add-back / OBE2109 dose 3 (200mg) + Add-back<br>At W24, half of the patients switched to active treatment, while half remained on Placebo; the switch was defined at randomization. | Drug: OBE2109<br>* OBE2109 100mg tablets for oral administration once daily<br>Drug: Placebo to match OBE2109<br>* Placebo to match OBE2109 100mg tablets for oral administration once daily<br>Drug: Placebo to match Add-back<br>* Placebo to match Add-back (E2 1 mg / NETA 0.5 mg) for oral administration once daily<br>Drug: Add-back<br>* Add-back (E2 1 mg / NETA 0.5 mg) 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 Responders based on menstrual blood loss (MBL) volume reduction at Week 24 | Assessed using the alkaline hematin method | From baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reduced menstrual blood loss | Assessed using the alkaline hematin method | Up to Week 52 | 
| Amenorrhea | Assessed using the alkaline hematin method | Up to Week 52 | 
| Time to amenorrhea |  | Up to Week 52 | 
| Number of days of uterine bleeding for the last 28-day interval prior to Week 24 | Assessed using the alkaline hematin method | last 28-day interval prior to Week 24 | 
| Number of days of uterine bleeding for each 28-day interval | Assessed using the alkaline hematin method | Up to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uterine Fibroid, Leiomyomata, Heavy Menstrual Bleeding, HMB, Heavy Uterine Bleeding, Menorrhagia, OBE2109 + Add-back