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

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.

• OBE2109 (Drug): OBE2109 100mg tablets for oral administration once daily
• Placebo to match OBE2109 (Drug): Placebo to match OBE2109 100mg tablets for oral administration once daily
• Placebo to match Add-back (Drug): Placebo to match Add-back (E2 1 mg / NETA 0.5 mg) for oral administration once daily
• Add-back (Drug): Add-back (E2 1 mg / NETA 0.5 mg) for oral administration once daily

Primary outcomes

• Percentage of Responders based on menstrual blood loss (MBL) volume reduction at Week 24 [From baseline to Week 24]: Assessed using the alkaline hematin method

Secondary outcomes

• Time to reduced menstrual blood loss [Up to Week 52]: Assessed using the alkaline hematin method
• Amenorrhea [Up to Week 52]: Assessed using the alkaline hematin method
• Time to amenorrhea [Up to Week 52]
• Number of days of uterine bleeding for the last 28-day interval prior to Week 24 [last 28-day interval prior to Week 24]: Assessed using the alkaline hematin method
• Number of days of uterine bleeding for each 28-day interval [Up to Week 52]: Assessed using the alkaline hematin method

Other outcomes

• Bone Mineral Density (BMD) [From baseline up to Week 76]: Assessed by dual-energy X-ray absorptiometry (DXA) scan
• Endometrial biopsy [From baseline up to Week 52]: Assessed by histology
• Adverse events [Up to Week 76]: Frequency and severity of Treatment-Emergent Adverse Events

Sex: Female, ages: 18 Years to any

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.

16 more sites not listed.

• Results publication: Donnez J, Petraglia F, Taylor H, Becker CM, Becker S, Herrera FC, Bestel E, Hori S, Dolmans MM. Linzagolix with and without hormonal add-back therapy for symptomatic uterine fibroids: PRIMROSE 1 & 2 long-term extension and withdrawal study. Fertil Steril. 2025 Oct;124(4):737-748. doi: 10.1016/j.fertnstert.2025.06.016. Epub 2025 Jun 19. PMID 40543832
• Results publication: Becker S, Dolmans MM, Herrera FC, Petraglia F, Renner SP, Ionescu-Ittu R, St-Pierre J, Boolell M, Bestel E, Hori S, Donnez J. Pain Reduction in Linzagolix-Treated Patients With Uterine Fibroids: A Secondary Mediation Analysis of the PRIMROSE 1 and 2 Phase 3 Trials. BJOG. 2025 Aug;132(9):1297-1306. doi: 10.1111/1471-0528.18190. Epub 2025 May 6. PMID 40326221
• Results publication: Donnez J, Taylor HS, Stewart EA, Bradley L, Marsh E, Archer D, Al-Hendy A, Petraglia F, Watts N, Gotteland JP, Bestel E, Terrill P, Loumaye E, Humberstone A, Garner E. Linzagolix with and without hormonal add-back therapy for the treatment of symptomatic uterine fibroids: two randomised, placebo-controlled, phase 3 trials. Lancet. 2022 Sep 17;400(10356):896-907. doi: 10.1016/S0140-6736(22)01475-1. PMID 36116480

• ObsEva SA, Study director, Geneva