Efficacy and Safety of Linzagolix for the Treatment of Endometriosis-associated Pain.

Phase 3

Completed

• 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: NCT03992846
• 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: 2019-06-13
• Study First Submitted: 2019-06-18
• Study First Submitted QC: 2019-06-18
• Study First Posted: 2019-06-20
• Primary Completion: 2021-10-18
• Study Completion: 2022-04-01
• Status Verified: 2022-06
• Results First Submitted: 2024-04-03
• Results First Submitted QC: 2024-05-01
• Results First Posted: 2024-05-29
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-04-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 486

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. -

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

Primary Outcome Measures

Name	Time	Method
Reduction of Dysmenorrhea (DYS) at Month 3 - Proportion of Responders	Baseline to Month 3	Percentage of subjects with reduction of 1.1 for DYS in mean pelvic pain score within last 28 days prior to Month 3 or discontinuation, and stable or decreased use of analgesics for Endometriosis-associated pain (=EAP) within the same calendar days.
Reduction of Non-menstrual Pelvic Pain (NMPP) at Month 3 - Proportion of Responders	Baseline to Month 3	Percentage of subjects with reduction of 0.8 for NMPP in mean pelvic pain score within last 28 days prior to Month 3 or discontinuation, and stable or decreased use of analgesics for Endometriosis-associated pain (=EAP) within the same calendar days.

Trial Locations

Locations (71)

Wellington Anti-Aging, LLC/ ID # 613; 🇺🇸 Loxahatchee Groves, Florida, United States

AKH Vienna University of Medicine Vienna / ID # 101; 🇦🇹 Vienna, Austria

MUDr Jan Drahonovsky, Ustav pro peci o matku a dite/ ID #163; 🇨🇿 Praha 4, Czechia

Southern Clinical Research / ID # 611; 🇺🇸 Metairie, Louisiana, United States

Gynekologicko - Porodnicka Ambulance/ ID # 162; 🇨🇿 Tábor, Czechia

Maternity Hospital № 3/ ID # 507; 🇺🇦 Zaporizhzhya, Ukraine

The Center for Women's Health & Wellnes/ ID # 603; 🇺🇸 Lawrenceville, New Jersey, United States

MHAT Dr. Bratan Shukerov / ID #138; 🇧🇬 Smolyan, Bulgaria

Gynekologie MU Dr.Lubomir Mikulasek / ID # 160; 🇨🇿 Ujezd nad Lesy, Czechia

CHRU Besançon Hopital/ ID # 204; 🇫🇷 Besançon, France

CHRU Strasbourg - Hopital Hautepierre/ ID # 205; 🇫🇷 Strasbourg, France

Clinique Pasteur / ID # 206; 🇫🇷 Toulouse, France

Róbert Károly Magánkórház/ ID # 253; 🇭🇺 Budapest, Hungary

Szent Anna Szuleszeti-Nogyogyaszati/ ID # 251; 🇭🇺 Debrecen, Hungary

Mediroyal Prevencios Kozpont/ ID # 252; 🇭🇺 Kecskemét, Hungary

Prywatna Klinika Ginekologiczno - Położnicza/ ID # 404; 🇵🇱 Białystok, Podlaskie, Poland

VITA LONGA Sp. z o.o./ ID # 408; 🇵🇱 Katowice, Poland

Indywidualna Specjalistyczna Praktyka Lekarska Krzysztof Wilk/ ID # 411; 🇵🇱 Katowice, Poland

Clinical Medical Research sp. Z o. O/ ID # 406; 🇵🇱 Katowice, Poland

Niepubliczny Zaklad Opieki Zrowotnej GynCentrum/ ID # 407; 🇵🇱 Katowice, Poland

Kotarski Jan Specjalistyczny Gabinet Ginekologiczno Polozniczy/ ID # 405; 🇵🇱 Lublin, Poland

Centrum Medyczne Chodźki Lublin/ ID # 403; 🇵🇱 Lublin, Poland

Centrum Ginekologii Endokrynologii i Medycyny Rozrodu "Artemida"/ ID # 409; 🇵🇱 Olsztyn, Poland

Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu/ ID # 410; 🇵🇱 Przemyśl, Poland

Specjalistyczny Gabinet Lekarski Krzysztof Dynowski / ID # 401; 🇵🇱 Warsaw, Poland

Quantum Medical Center SRL/ ID # 353; 🇷🇴 Bucharest, Romania

Centrul Medical EUROMED/ ID # 351; 🇷🇴 Bucuresti, Romania

Gine Plus SRL Cluj- Napoca/ ID # 357; 🇷🇴 Cluj-Napoca, Romania

Centrul Medical GALENUS/ ID # 355; 🇷🇴 Târgu-Mureş, Romania

Hospital General Universitario Reina Sofia/ ID # 304; 🇪🇸 Murcia, Spain

Hospital Regional Universitario de Málaga/ ID # 303; 🇪🇸 Málaga, Spain

Ivano-Frankivsk regional perinatal center, Family planning center/ ID # 506; 🇺🇦 Ivano-Frankivs'k, Ukraine

Medical center of LLC "Medical Center "Verum"/ ID # 503; 🇺🇦 Kyiv, Ukraine

Institute of Pediatrics Obstetrics and Gynecology/ ID # 508; 🇺🇦 Kyiv, Ukraine

Kyiv City Maternity Hospital #6/ ID # 504; 🇺🇦 Kyiv, Ukraine

Kyiv City Clinical Hospital #9/ ID # 501; 🇺🇦 Kyiv, Ukraine

Kyiv City Center of Reproductive and Perinatal Medicine/ ID # 509; 🇺🇦 Kyiv, Ukraine

Ternopil' Communal City Hospital #2/ ID # 511; 🇺🇦 Ternopil, Ukraine

Vinnytsia City Clinical Hospital "Center of Mother and the Child "/ ID # 510; 🇺🇦 Vinnytsia, Ukraine

Zaporizhzhya Regional Clinical Hospital/ ID # 505; 🇺🇦 Zaporizhzhya, Ukraine

Chattanooga Medical Research LLC/ ID# 602; 🇺🇸 Chattanooga, Tennessee, United States

Next Innovative Clinical Research/ ID # 617; 🇺🇸 Houston, Texas, United States

Storks Research, LLC/ ID # 623; 🇺🇸 Sugar Land, Texas, United States

Women's & Family Care, LLC dba GTC Research/ ID # 608; 🇺🇸 Shawnee Mission, Kansas, United States

Choice Research, LLC/ ID # 609; 🇺🇸 Dothan, Alabama, United States

Affinity Clinical Research Institute/ ID # 622; 🇺🇸 Oak Brook, Illinois, United States

Quad Clinical Research LLC/ ID # 615; 🇺🇸 Saint Louis, Missouri, United States

PMG Research of Wilmington/ ID # 614; 🇺🇸 Wilmington, North Carolina, United States

UWCR - Lyndhurst Clinical Researc/ ID# 605; 🇺🇸 Winston-Salem, North Carolina, United States

Obstetrics & Gynecology Associates, Inc./ ID# 606; 🇺🇸 Fairfield, Ohio, United States

Achieve Clinical Research/ ID # 601; 🇺🇸 Birmingham, Alabama, United States

Multiprofile Hospital for Active Treatment Sliven/ ID # 131; 🇧🇬 Sliven, Bulgaria

Multiprofile Hospital for Active Treatment St. Sofia/ ID # 137; 🇧🇬 Sofia, Bulgaria

Lubelskie Centrum Diagnostyczne/ ID # 402; 🇵🇱 Świdnik, Lubelskie, Poland

Multi-Specialty Research Associates, Inc./ ID # 625; 🇺🇸 Lake City, Florida, United States

Adventura Clinical Research/ ID # 616; 🇺🇸 Miramar, Florida, United States

Invocare Medical Research & Healthcare Center/ ID # 607; 🇺🇸 West Columbia, South Carolina, United States

University Multiprofile Hospital for Active Treatment "Sofiamed"/ ID # 133; 🇧🇬 Sofia, Bulgaria

Spitalul Clinic "Nicolae Malaxa"/ ID # 352; 🇷🇴 Bucharest, Romania

Salzburger Landeskliniken / ID # 105; 🇦🇹 Salzburg, Austria

Southeast Clinical Research/ ID # 618; 🇺🇸 Chiefland, Florida, United States

Advanced Specialty Research/ ID # 610; 🇺🇸 Nampa, Idaho, United States

Stedman Clinical Trials/ ID # 612; 🇺🇸 Tampa, Florida, United States

AKH Vienna University of Medicine Vienna/ ID # 103; 🇦🇹 Vienna, Austria

Principal SMO Kft/ ID # 250; 🇭🇺 Baja, Bacs-Kiskun, Hungary

Sp Cl de Obstetrica si Ginecologie "Prof. Dr. Panait Sirbu"/ ID # 354; 🇷🇴 Bucuresti, Romania

Tanner Clinic/ ID # 624; 🇺🇸 Layton, Utah, United States

Medical Centre Excelsior /ID # 135; 🇧🇬 Sofia, Bulgaria

Group Practice for Specialized Medical Assistance in GINART/ ID # 132; 🇧🇬 Sofia, Bulgaria

City clinical maternity hospital №1/ ID # 502; 🇺🇦 Chernivtsi, Ukraine

Universal Axon - Homestead, LLC/ ID # 620; 🇺🇸 Homestead, Florida, United States