A Phase 3 Study to Confirm the Efficacy and Safety of Linzagolix to Treat Endometriosis-associated Pain

Phase 3

Terminated

• Conditions: Endometriosis
• Interventions: Drug: 200 mg linzagolix tablet; Drug: 75 mg linzagolix tablet; Drug: Placebo tablet to match 200 mg linzagolix tablet; Drug: Add-back capsule (E2 1 mg / NETA 0.5 mg); Drug: Placebo tablet to match 75 mg linzagolix tablet; Drug: Placebo capsule to match Add-back capsule

• Registration Number: NCT03986944
• Lead Sponsor: Kissei Pharmaceutical Co., Ltd.

Brief Summary

The primary objective of this study is to demonstrate the efficacy and safety of linzagolix administered orally once daily for 3 months at a dose of 75 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, in the management of moderate to severe endometriosis-associated pain (EAP).

Detailed Description

This is a prospective, randomized, double-blind, placebo-controlled study to demonstrate the efficacy and safety of linzagolix administered orally once daily at doses of 75 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 450 women.

Eligible subjects who have completed the 6-month treatment period may enter a separate extension study for 6 additional months of active treatment (no placebo control). Subjects who do not continue in the extension study will enter a 6 month treatment-free follow-up phase.

Study Timeline

• Study Start: 2019-05-23
• Study First Submitted: 2019-06-06
• Study First Submitted QC: 2019-06-13
• Study First Posted: 2019-06-14
• Primary Completion: 2021-01-06
• Study Completion: 2021-02-16
• Status Verified: 2022-05
• Results First Submitted: 2024-03-18
• Results First Submitted QC: 2024-10-27
• Results First Posted: 2024-10-29
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-04-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 85

Inclusion Criteria

The subject must have:

• Her most recent surgical and - if available - histological diagnosis of pelvic endometriosis up to 10 years before screening.
• Moderate to severe endometriosis-associated pain during the screening period.
• Regular menstrual cycles.
• BMI ≥ 18 kg/m2 at the screening visit.

Key

Exclusion Criteria

The subject will be excluded if she:

• Is pregnant or breast feeding or is planning a pregnancy within the duration of the treatment period of the study.
• Is less than 6 months postpartum or 3 months postabortion/ miscarriage at the time of entry into the screening period.
• Has had a surgical history of any major abdominal surgery within 6 months or any interventional surgery for endometriosis performed within a period of 2 months before screening.
• Did not respond to prior treatment with GnRH agonists or GnRH antagonists for endometriosis.
• Has a history of, or known, osteoporosis or other metabolic bone disease.
• Has chronic pelvic pain that is not caused by endometriosis and requires chronic analgesic or other chronic therapy which would interfere with the assessment of endometriosis-associated pain.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Linzagolix 200 mg + Add-back (E2 1 mg / NETA 0.5 mg)	Placebo tablet to match 75 mg linzagolix tablet	-
Placebo	Placebo tablet to match 75 mg linzagolix tablet	-
Placebo	Placebo tablet to match 200 mg linzagolix tablet	-
Linzagolix 200 mg + Add-back (E2 1 mg / NETA 0.5 mg)	200 mg linzagolix tablet	-
Placebo	Placebo capsule to match Add-back capsule	-
Linzagolix 75 mg	Placebo tablet to match 200 mg linzagolix tablet	-
Linzagolix 75 mg	Placebo capsule to match Add-back capsule	-
Linzagolix 75 mg	75 mg linzagolix tablet	-
Linzagolix 200 mg + Add-back (E2 1 mg / NETA 0.5 mg)	Add-back capsule (E2 1 mg / NETA 0.5 mg)	-

Primary Outcome Measures

Name	Time	Method
Dysmenorrhea	Baseline to Month 3	Change at Month 3 from baseline in the mean daily assessment of dysmenorrhea (DYS) measured on a 4-point Verbal Rating Scale (VRS) using an electronicdiary; * The 4-point VRS scale for DYS ranges from 0 to 3 (0: No pain; 1: Mild pain; 2: Moderate pain; 3: Severe pain).; * A negative change in scores would be indicative of an improvement in the pain of DYS.
Non-menstrual Pelvic Pain	Baseline to Month 3	Change at Month 3 from baseline in the mean daily assessment of non-menstrual pelvic pain (NMPP) measured on a 4-point Verbal Rating Scale (VRS) using anelectronic diary; * The 4-point VRS scale for NMPP ranges from 0 to 3 (0: No pain; 1: Mild pain; 2: Moderate pain; 3: Severe pain).; * A negative change in scores would be indicative of an improvement in the NMPP.

Trial Locations

Locations (112)

Birmingham OBGYN / ID # 740; 🇺🇸 Birmingham, Alabama, United States

Mesa Obstetricians and Gyneocologists / ID # 790; 🇺🇸 Mesa, Arizona, United States

Precision Trials AZ, LLC / ID # 783; 🇺🇸 Phoenix, Arizona, United States

Quality of LIfe Medical & Research Center, LLC / ID # 813; 🇺🇸 Tucson, Arizona, United States

Visions Clinical Research-Tucson / ID # 754; 🇺🇸 Tucson, Arizona, United States

Lynn Institute of the Ozarks / ID # 826; 🇺🇸 Little Rock, Arkansas, United States

Applied Research Center of Arkansas / ID # 735; 🇺🇸 Little Rock, Arkansas, United States

Join Clinical Trials / ID # 778; 🇺🇸 Huntington Park, California, United States

Long Beach Clinical Trials, LLC / ID # 768; 🇺🇸 Long Beach, California, United States

Matrix Clinical Research / ID # 751; 🇺🇸 Los Angeles, California, United States

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