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

A Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled, Clinical Study to Assess the Efficacy and Safety of Linzagolix in Subjects With Moderate to Severe Endometriosis-associated Pain.

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).

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 486
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • Salzburger Landeskliniken / ID # 105
  • Vienna, Austria, 1090
    • AKH Vienna University of Medicine Vienna / ID # 101
  • Vienna, Austria, 1090
    • AKH Vienna University of Medicine Vienna/ ID # 103
• Bulgaria
  • Sliven, Bulgaria, 8800
    • Multiprofile Hospital for Active Treatment Sliven/ ID # 131
  • Smolyan, Bulgaria
    • MHAT Dr. Bratan Shukerov / ID #138
  • Sofia, Bulgaria, 1407
    • Medical Centre Excelsior /ID # 135
  • Sofia, Bulgaria, 1606
    • Group Practice for Specialized Medical Assistance in GINART/ ID # 132
  • Sofia, Bulgaria, 1797
    • University Multiprofile Hospital for Active Treatment "Sofiamed"/ ID # 133
  • Sofia, Bulgaria, 1618
    • Multiprofile Hospital for Active Treatment St. Sofia/ ID # 137
• Czechia
  • Praha 4, Czechia, 14700
    • MUDr Jan Drahonovsky, Ustav pro peci o matku a dite/ ID #163
  • Tábor, Czechia, 39003
    • Gynekologicko - Porodnicka Ambulance/ ID # 162
  • Ujezd nad Lesy, Czechia, 19016
    • Gynekologie MU Dr.Lubomir Mikulasek / ID # 160
• France
  • Besançon, France, 25000
    • CHRU Besançon Hopital/ ID # 204
  • Strasbourg, France, 67200
    • CHRU Strasbourg - Hopital Hautepierre/ ID # 205
  • Toulouse, France, 31076
    • Clinique Pasteur / ID # 206
• Hungary
  • Budapest, Hungary, 1135
    • Róbert Károly Magánkórház/ ID # 253
  • Debrecen, Hungary, 4024
    • Szent Anna Szuleszeti-Nogyogyaszati/ ID # 251
  • Kecskemét, Hungary, 6000
    • Mediroyal Prevencios Kozpont/ ID # 252
  • Bacs-Kiskun
    • Baja, Bacs-Kiskun, Hungary, 6500
      • Principal SMO Kft/ ID # 250
• Poland
  • Katowice, Poland, 40-301
    • Indywidualna Specjalistyczna Praktyka Lekarska Krzysztof Wilk/ ID # 411
  • Katowice, Poland, 40-851
    • Niepubliczny Zaklad Opieki Zrowotnej GynCentrum/ ID # 407
  • Katowice, Poland, 20-093
    • VITA LONGA Sp. z o.o./ ID # 408
  • Katowice, Poland, 40-001
    • Clinical Medical Research sp. Z o. O/ ID # 406
  • Lublin, Poland, 20-064
    • Kotarski Jan Specjalistyczny Gabinet Ginekologiczno Polozniczy/ ID # 405
  • Lublin, Poland, 20-093
    • Centrum Medyczne Chodźki Lublin/ ID # 403
  • Olsztyn, Poland, 10-357
    • Centrum Ginekologii Endokrynologii i Medycyny Rozrodu "Artemida"/ ID # 409
  • Przemyśl, Poland, 37-700
    • Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu/ ID # 410
  • Warsaw, Poland, 02-929
    • Specjalistyczny Gabinet Lekarski Krzysztof Dynowski / ID # 401
  • Lubelskie
    • Świdnik, Lubelskie, Poland, 21-040
      • Lubelskie Centrum Diagnostyczne/ ID # 402
  • Podlaskie
    • Białystok, Podlaskie, Poland, 15-224
      • Prywatna Klinika Ginekologiczno - Położnicza/ ID # 404
• Romania
  • Bucharest, Romania, 12071
    • Quantum Medical Center SRL/ ID # 353
  • Bucharest, Romania, 22448
    • Spitalul Clinic "Nicolae Malaxa"/ ID # 352
  • Bucuresti, Romania, 20764
    • Centrul Medical EUROMED/ ID # 351
  • Bucuresti, Romania, 60251
    • Sp Cl de Obstetrica si Ginecologie "Prof. Dr. Panait Sirbu"/ ID # 354
  • Cluj-Napoca, Romania, 400698
    • Gine Plus SRL Cluj- Napoca/ ID # 357
  • Târgu-Mureş, Romania, 540236
    • Centrul Medical GALENUS/ ID # 355
• Spain
  • Murcia, Spain, 30003
    • Hospital General Universitario Reina Sofia/ ID # 304
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Málaga/ ID # 303
• Ukraine
  • Chernivtsi, Ukraine, 58003
    • City clinical maternity hospital №1/ ID # 502
  • Ivano-Frankivs'k, Ukraine, 76018
    • Ivano-Frankivsk regional perinatal center, Family planning center/ ID # 506
  • Kyiv, Ukraine, 02125
    • Kyiv City Maternity Hospital #6/ ID # 504
  • Kyiv, Ukraine, 03039
    • Medical center of LLC "Medical Center "Verum"/ ID # 503
  • Kyiv, Ukraine, 04050
    • Institute of Pediatrics Obstetrics and Gynecology/ ID # 508
  • Kyiv, Ukraine, 04112
    • Kyiv City Clinical Hospital #9/ ID # 501
  • Kyiv, Ukraine, 04210
    • Kyiv City Center of Reproductive and Perinatal Medicine/ ID # 509
  • Ternopil, Ukraine, 46400
    • Ternopil' Communal City Hospital #2/ ID # 511
  • Vinnytsia, Ukraine, 21019
    • Vinnytsia City Clinical Hospital "Center of Mother and the Child "/ ID # 510
  • Zaporizhzhya, Ukraine, 69000
    • Zaporizhzhya Regional Clinical Hospital/ ID # 505
  • Zaporizhzhya, Ukraine, 69071
    • Maternity Hospital № 3/ ID # 507
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35218
      • Achieve Clinical Research/ ID # 601
    • Dothan, Alabama, United States, 36303
      • Choice Research, LLC/ ID # 609
  • Florida
    • Chiefland, Florida, United States, 32626
      • Southeast Clinical Research/ ID # 618
    • Homestead, Florida, United States, 33030
      • Universal Axon - Homestead, LLC/ ID # 620
    • Lake City, Florida, United States, 32055
      • Multi-Specialty Research Associates, Inc./ ID # 625
    • Loxahatchee Groves, Florida, United States, 33470
      • Wellington Anti-Aging, LLC/ ID # 613
    • Miramar, Florida, United States, 33012
      • Adventura Clinical Research/ ID # 616
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials/ ID # 612
  • Idaho
    • Nampa, Idaho, United States, 83687
      • Advanced Specialty Research/ ID # 610
  • Illinois
    • Oak Brook, Illinois, United States, 60523
      • Affinity Clinical Research Institute/ ID # 622
  • Kansas
    • Shawnee Mission, Kansas, United States, 66218
      • Women's & Family Care, LLC dba GTC Research/ ID # 608
  • Louisiana
    • Metairie, Louisiana, United States, 70001
      • Southern Clinical Research / ID # 611
  • Missouri
    • Saint Louis, Missouri, United States, 63109
      • Quad Clinical Research LLC/ ID # 615
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • The Center for Women's Health & Wellnes/ ID # 603
  • North Carolina
    • Wilmington, North Carolina, United States, 28412
      • PMG Research of Wilmington/ ID # 614
    • Winston-Salem, North Carolina, United States, 27103
      • UWCR - Lyndhurst Clinical Researc/ ID# 605
  • Ohio
    • Fairfield, Ohio, United States, 45014
      • Obstetrics & Gynecology Associates, Inc./ ID# 606
  • South Carolina
    • West Columbia, South Carolina, United States, 29169
      • Invocare Medical Research & Healthcare Center/ ID # 607
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Medical Research LLC/ ID# 602
  • Texas
    • Houston, Texas, United States, 77021
      • Next Innovative Clinical Research/ ID # 617
    • Sugar Land, Texas, United States, 77479
      • Storks Research, LLC/ ID # 623
  • Utah
    • Layton, Utah, United States, 84041
      • Tanner Clinic/ ID # 624

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo tablet to match 200 mg linzagolix tablet; For oral administration once daily; Drug: Placebo capsule to match Add-back capsule; For oral administration once daily; Drug: Placebo tablet to match 75 mg linzagolix tablet; For oral administration once daily
Experimental: Linzagolix 75 mg	Drug: 75 mg linzagolix tablet; For oral administration once daily; Drug: Placebo tablet to match 200 mg linzagolix tablet; For oral administration once daily; Drug: Placebo capsule to match Add-back capsule; For oral administration once daily
Experimental: Linzagolix 200 mg + Add-back (E2 1 mg / NETA 0.5 mg)	Drug: 200 mg linzagolix tablet; For oral administration once daily; Drug: Placebo tablet to match 75 mg linzagolix tablet; For oral administration once daily; Drug: Add-back capsule (E2 1 mg / NETA 0.5 mg); For oral administration once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dysmenorrhea	Change at Month 3 from baseline in the mean daily assessment of dysmenorrhea measured on a 0-3 Verbal Rating Scale (VRS) using an electronic diary. The lower value represents a better outcome.	Baseline to Month 3
Non-menstrual pelvic pain	Change at Month 3 from baseline in the mean daily assessment of non-menstrual pelvic pain measured on a 0-3 Verbal Rating Scale (VRS) using an electronic diary. The lower value represents a better outcome.	Baseline to Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dysmenorrhea	Change from baseline to Month 6 in dysmenorrhea measured on a 0-3 Verbal Rating Scale (VRS) using an electronic diary. The lower value represents a better outcome.	Baseline to Month 6
Non-menstrual pelvic pain	Change from baseline to Month 6 in non-menstrual pelvic pain measured on a 0-3 Verbal Rating Scale (VRS) using an electronic diary. The lower value represents a better outcome	Baseline to Month 6
Dyschezia	Change from baseline to Month 6 in dyschezia measured on a 0-10 Numeric Rating Scale (NRS) using an electronic diary. The lower value represents a better outcome.	Baseline to Month 6
Overall Pelvic Pain	Change from baseline to Month 6 in overall pelvic pain measured on a 0-10 Numeric Rating Scale (NRS) using an electronic diary. The lower value represents a better outcome.	Baseline to Month 6
Interference of pain with the ability to perform daily activities	Change from baseline to Month 6 in the interference of pain with the ability to perform daily activities, measured using the pain dimension of the Endometriosis Health Profile-30 (EHP-30) using an electronic diary	Baseline to Month 6
Dyspareunia	Change from baseline to Month 6 in dyspareunia measured on a 0-3 Verbal Rating Scale (VRS) using an electronic diary. The lower value represents a better outcome.	Baseline to Month 6
No analgesic use for endometriosis associated pain	Proportion of subjects reporting no analgesic use for endometriosis associated pain, during the preceding 4-week period at Month 6	During the preceding 4-week period at Month 6
No opiate use for endometriosis associated pain	Proportion of subjects reporting no opiate use for endometriosis associated pain, during the preceding 4-week period at Month 6	During the preceding 4-week period at Month 6

Collaborators and Investigators

• Sponsor: Kissei Pharmaceutical Co., Ltd.
• Investigators: Study Director: Lecomte, ObsEva SA

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2019
• Primary Completion (Actual): October 18, 2021
• Study Completion (Actual): April 1, 2022

Study Registration Dates

• First Submitted: June 18, 2019
• First Submitted That Met QC Criteria: June 18, 2019
• First Posted (Actual): June 20, 2019

Study Record Updates

• Last Update Posted (Estimate): January 13, 2023
• Last Update Submitted That Met QC Criteria: January 12, 2023
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Dysmenorrhea; Dyschezia; Dyspareunia; Non-menstrual pelvic pain
• Additional Relevant MeSH Terms: Endometriosis
• Other Study ID Numbers: 18-OBE2109-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No