A Phase 3 Study to Confirm the Efficacy and Safety of Linzagolix to Treat 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: Terminated
• 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): 85
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Red Deer, Alberta, Canada, T4N 6V7
      • CARe Clinic / ID # 872
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • McMaster University Medical Centre / ID # 870
    • Windsor, Ontario, Canada, N8N C52
      • Victory Reproductive Care / ID # 873
• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Ponce Medical SChool Foundation Inc./ CAIMED Center / ID # 891
  • Ponce, Puerto Rico, 00717
    • Puerto Rico Medical Research Inc. / ID # 890
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Birmingham OBGYN / ID # 740
  • Arizona
    • Mesa, Arizona, United States, 85209
      • Mesa Obstetricians and Gyneocologists / ID # 790
    • Phoenix, Arizona, United States, 85032
      • Precision Trials AZ, LLC / ID # 783
    • Tucson, Arizona, United States, 85712
      • Quality of LIfe Medical & Research Center, LLC / ID # 813
    • Tucson, Arizona, United States, 85712
      • Visions Clinical Research-Tucson / ID # 754
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Lynn Institute of the Ozarks / ID # 826
    • Little Rock, Arkansas, United States, 72212
      • Applied Research Center of Arkansas / ID # 735
  • California
    • Huntington Park, California, United States, 90255
      • Join Clinical Trials / ID # 778
    • Long Beach, California, United States, 90806
      • Long Beach Clinical Trials, LLC / ID # 768
    • Los Angeles, California, United States, 90057
      • Matrix Clinical Research / ID # 751
    • Norwalk, California, United States, 90650
      • Futura Research, Org / ID # 781
    • Panorama City, California, United States, 91402
      • National Research Institute / ID # 805
    • San Diego, California, United States, 92114
      • Precision Research Institute / ID # 792
    • San Diego, California, United States, 92119
      • MD Strategies Research Centers / ID # 765
  • Colorado
    • Denver, Colorado, United States, 80209
      • Downtown Women's Health Care / ID # 718
    • Greenwood Village, Colorado, United States, 80111
      • Center for Women's Health / ID # 761
    • Lakewood, Colorado, United States, 80228
      • Physicians Research Options, LLC / Red Rocks Ob/Gyn / ID # 732
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Dr. David I. Lubetkin, LLC / ID # 703
    • Boynton Beach, Florida, United States, 33435
      • Helix Biomedics Clincial Research, LLC / ID # 750
    • DeLand, Florida, United States, 32720
      • Accel Research Sites, DeLand Clinical Research Unit / ID # 713
    • Doral, Florida, United States, 33166
      • Universal Axon Clinical Research / ID # 769
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc. / ID # 773
    • Margate, Florida, United States, 33063
      • South Florida Clinical Research Institute / ID # 747
    • Miami, Florida, United States, 33135
      • Coral Way Research / ID # 799
    • Miami, Florida, United States, 33155
      • La Salud Research Clinic, Inc. / ID # 824
    • Miami, Florida, United States, 33135
      • Suncoast Research Group, LLC / ID # 756
    • Miami, Florida, United States, 33155
      • Biotech Pharmaceutical Group LLC / ID # 786
    • Miami, Florida, United States, 33176
      • Suncoast Research Associates, LLC / ID # 760
    • Miami, Florida, United States, 33196-1554
      • LCC Medical Research Institute / ID # 814
    • Miami Lakes, Florida, United States, 33016
      • Global Health Research Center, Inc. / ID # 787
    • Ocoee, Florida, United States, 34761
      • Sensible Healthcare / ID # 749
    • Orange City, Florida, United States, 32763
      • A Premier Medical Research of Florida, LLC / ID # 752
    • Orlando, Florida, United States, 32806
      • Clinical Associates of Orlando, LLC / ID # 779
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc. / ID # 731
    • Orlando, Florida, United States, 32806-1133
      • Omega Research Orlando, LLC / ID # 785
    • Orlando, Florida, United States, 32806
      • Synexus Clinical Research US, Inc. / ID # 725
    • Sarasota, Florida, United States, 34239
      • Physician Care Clinical Research LLC / ID # 810
    • Tampa, Florida, United States, 33606
      • University of South Florida / ID # 738
    • Tampa, Florida, United States, 33609
      • GCP Clinical Research, LLC / ID # 825
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Atlanta Women's Research Institute, Inc. / ID # 727
  • Idaho
    • Meridian, Idaho, United States, 83646
      • Sonara Clinical Research, LLC / ID # 720
  • Illinois
    • Chicago, Illinois, United States, 60605
      • Moore Health Wellness Research Institute, LLC / ID # 795
    • Evergreen Park, Illinois, United States, 60805
      • Providea Health Partners LLC / ID # 734
  • Kansas
    • Wichita, Kansas, United States, 67226
      • Cypress Medical Research Center, LLC / ID # 755
  • Louisiana
    • Eunice, Louisiana, United States, 70535-5100
      • Horizon Research Group of Opelousas, LLC / ID # 757
    • Marrero, Louisiana, United States, 70072
      • Praetorian Pharmaceutical Research / ID # 739
    • New Orleans, Louisiana, United States, 70125
      • Women Under Study, LLC / ID # 820
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University, School Of Medicine / ID # 816
    • Baltimore, Maryland, United States, 21208
      • Pharmasite Research Inc / ID # 838
    • Towson, Maryland, United States, 21204
      • Continental Clinical Solutions, LLC / ID # 777
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
      • NECCR Fall River, LLC / Id # 712
  • Michigan
    • Flint, Michigan, United States, 48532
      • Onyx Clinical Research / ID # 793
    • Saginaw, Michigan, United States, 48602
      • Valley OBGYN / ID # 704
    • Saginaw, Michigan, United States, 48602
      • CMEP/CMU health / ID # 812
    • Saginaw, Michigan, United States, 48604
      • Saginaw Valley Medical Research Group, LLC / ID # 743
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Office of Edmond Pack, MD / Id # 818
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • Lawrence OB/GYN clinical Research, LLC / ID # 742
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials, Inc. / ID # 707
  • North Carolina
    • Fayetteville, North Carolina, United States, 28304
      • Carolina Institute for Clinical Research / ID # 728
    • Greensboro, North Carolina, United States, 27408
      • Unified Women's Clinical Research - Green Valley OBGYN / ID # 719
    • New Bern, North Carolina, United States, 28562
      • Eastern Carolina Women's Center / Id # 794
    • Raleigh, North Carolina, United States, 27607
      • Unified Women's Clinical Research - Raleigh / Id # 714
    • Winston-Salem, North Carolina, United States, 27103
      • Carolina Medical Trials, LLC / ID # 788
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Complete Healthcare for Women / ID # 801
    • Columbus, Ohio, United States, 43213
      • ClinOhio Research Services, LLC / ID # 722
    • Dayton, Ohio, United States, 45409
      • Wright State Physicians / ID # 733
    • Franklin, Ohio, United States, 45005
      • Hilltop OBGYN / ID # 711
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University / ID # 791
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • OB/GYN Associates of Erie / ID # 706
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Health Milton S. Hershey Medical Center / ID # 804
    • Jenkintown, Pennsylvania, United States, 19046
      • The Clinical Trial Center / ID # 744
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • VitaLink Research - Upstate / ID # 789
    • North Charleston, South Carolina, United States, 29406
      • Clinical Trials of South Carolina / ID # 741
    • Spartanburg, South Carolina, United States, 29303
      • VitaLink Research Spartanburg / ID # 753
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Seasons at Bristol / ID # 705
    • Chattanooga, Tennessee, United States, 37421
      • WR-ClinSearch, LLC / ID # 821
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center / ID # 780
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, Inc / ID # 772
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Associates Inc / ID # 802
  • Texas
    • Austin, Texas, United States, 78758
      • Austin Area ObGyn PLLC / ID # 701
    • Austin, Texas, United States, 78705
      • Women Partners in Health / ID # 836
    • Austin, Texas, United States, 78758
      • Christina Sebestyen MD, P.A. dba OBGYN North / ID # 764
    • Beaumont, Texas, United States, 77702
      • Christus St. Elizabeth Gadolin Research, LLC / ID # 774
    • Dallas, Texas, United States, 75231
      • HCWC dba DiscoveryClinical Trials / ID # 771
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center / ID # 823
    • Fort Worth, Texas, United States, 76104
      • Signature Gyn Services / ID # 726
    • Georgetown, Texas, United States, 78626
      • Georgetown OB/GYN / ID # 770
    • Houston, Texas, United States, 77008
      • Ventavia Research Group, LLC / ID # 729
    • Houston, Texas, United States, 77017
      • Vilo Research Group / ID # 709
    • Houston, Texas, United States, 77024
      • UT Health Clinical Res Ctr / ID # 828
    • Houston, Texas, United States, 77054
      • TMC Life Research, Inc. / ID # 809
    • Irving, Texas, United States, 75062
      • MacArthur OB-Gyn Research / ID # 840
    • Katy, Texas, United States, 77450
      • Medical Colleagues of Texas / ID # 819
    • Lampasas, Texas, United States, 76550
      • FMC Science / ID # 730
    • League City, Texas, United States, 77573
      • Maximos OB/GYN / ID # 737
    • McAllen, Texas, United States, 78503
      • DCT-McAllen Primary Care Research, LLC dba Discovery Clinical Trials / ID # 803
    • Pflugerville, Texas, United States, 78660
      • DCT-AACT, LLC dba Discovery Clinical Trials / ID # 815
    • Schertz, Texas, United States, 78154
      • Northeast Clinical Research of San Antonio, LLC / ID # 710
  • Utah
    • Draper, Utah, United States, 84020
      • Physicians Research Options PRO / ID # 766
    • Pleasant Grove, Utah, United States, 84062
      • Physicians' Res Options - PG / ID # 833
    • Salt Lake City, Utah, United States, 84107
      • Wasatch Clinical Research / ID # 746
    • Salt Lake City, Utah, United States, 84124
      • Highland Clinical Research / ID # 708
  • Virginia
    • Richmond, Virginia, United States, 23225
      • Clinical Research Partners, LLC / ID # 715
    • Richmond, Virginia, United States, 23235
      • Clinical Research Partners, LLC / ID # 775
    • Virginia Beach, Virginia, United States, 23456
      • Tidewater Clinical Research The Group for Women / ID # 716
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Women's: Health, Research, Gynecology / ID # 702
    • Seattle, Washington, United States, 98109
      • Seattle Reproductive Medicine / ID # 811

Participation Criteria

Eligibility Criteria

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

Description

Key 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 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 Verbal Rating Scale (VRS) using an electronic diary	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 Verbal Rating Scale (VRS) using an electronic diary	Baseline to Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Dysmenorrhea	Change from baseline to Month 6 in dysmenorrhea measured on a Verbal Rating Scale (VRS) using an electronic diary	Baseline to Month 6
Non-menstrual pelvic pain	Change from baseline to Month 6 in non-menstrual pelvic pain measured on a Verbal Rating Scale (VRS) using an electronic diary	Baseline to Month 6
Dyschezia	Change from baseline to Month 6 in dyschezia measured on a Numeric Rating Scale (NRS) using an electronic diary	Baseline to Month 6
Overall Pelvic Pain	Change from baseline to Month 6 in overall pelvic pain measured on a Numeric Rating Scale (NRS) using an electronic diary	Baseline to Month 6
Dyspareunia	Change from baseline to Month 6 in dyspareunia measured on a Verbal Rating Scale (VRS) using an electronic diary	Baseline to Month 6
Percentage change from baseline to Month 6 in Bone Mineral Density (BMD)	Percentage change from baseline to Month 6 of the BMD measured by dual-energy X-ray absorptiometry (DXA) scan of Lumbar Spine	Baseline to Month 6
Change from baseline to Month 6 in Bone Mineral Density (BMD)	Change from baseline to Month 6 of the BMD measured by dual-energy X-ray absorptiometry (DXA) scan of Lumbar Spine Z-scores	Baseline to Month 6
Clinical laboratory assessments: total cholesterol	Change from baseline to Month 6 in clinical laboratory assessments: total cholesterol	Baseline to Month 6
Clinical laboratory assessments: LDL	Change from baseline to Month 6 in clinical laboratory assessments: LDL cholesterol	Baseline to Month 6
Clinical laboratory assessments: triglycerides	Change from baseline to Month 6 in clinical laboratory assessments: Triglycerides	Baseline to Month 6
Change from baseline to Month 6 in the endometrial thickness	Change from baseline to Month 6 in endometrial thickness measured by Transvaginal Ultrasound (TVUS)	Baseline to Month 6
Change From Baseline to Month 6 in ECG results	Change from baseline to Month 6 in ECG results (QTcF values)	Baseline to Month 6

Collaborators and Investigators

• Sponsor: ObsEva SA
• Investigators: Study Director: Lecomte, ObsEva SA

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2019
• Primary Completion (Actual): January 6, 2021
• Study Completion (Actual): February 16, 2021

Study Registration Dates

• First Submitted: June 6, 2019
• First Submitted That Met QC Criteria: June 13, 2019
• First Posted (Actual): June 14, 2019

Study Record Updates

• Last Update Posted (Actual): May 11, 2022
• Last Update Submitted That Met QC Criteria: May 5, 2022
• Last Verified: May 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-OBE2109-002

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