Extension to Study on Efficacy and Safety of Linzagolix for the Treatment of Endometriosis-associated Pain (EDELWEISS 5)

A Double-blind Randomized Extension Study to Assess the Long-term Efficacy and Safety of Linzagolix in Subjects With Endometriosis-associated Pain

The primary objective of this extension study is to assess the maintenance of efficacy of linzagolix administered orally once daily for up to an additional 6 months (for up to 12 months of treatment in total) in women who have already completed 6 months of linzagolix treatment at a dose of 75 mg alone or of 200 mg in combination with ABT (E2 1 mg / NETA 0.5 mg), in the management of moderate to severe endometriosis-associated pain (EAP) in women with surgically confirmed endometriosis.

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 study. Subjects who have completed the 6-month Treatment Period in 18-OBE2109-002 - Edelweiss 2 study (herein referred to as main study) will be invited to enter the present extension study. Month 6 visit of the main study is a decision point for Subjects to either end treatment and enter a post-treatment follow up (part of the main study), or to opt for a 6-month treatment extension. All subjects will receive once daily either linzagolix 75 mg alone (with ABT placebo) or 200 mg combined with ABT for 6 months. Subjects who received placebo during the main study will be randomized to either linzagolix 75 mg alone (with ABT placebo) or linzagolix 200 mg with ABT. Subjects who received active treatment during the main study will continue with the same treatment. Double-dummy design will be used in order to maintain the blinding of the study.

After end of treatment in the extension study (6-month treatment period: from Month 6 to Month 12), subjects will enter a post-treatment Follow-Up Period of 6 months with no investigational medicinal product (IMP) or - for subjects willing to continue treatment - a second extension study will be proposed.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Red Deer, Alberta, Canada, T4N 6V7
      • CARe Clinic / ID # 872
• Puerto Rico
  • Ponce, Puerto Rico, 00717
    • Puerto Rico Medical Res Inc. / ID # 890
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72212
      • Applied Res Center of Ar / Id # 735
  • California
    • Norwalk, California, United States, 90650
      • Futura Research, Inc. / ID # 781
  • Colorado
    • Greenwood Village, Colorado, United States, 80111
      • Adv Womens Health Institute / ID # 761
    • Lakewood, Colorado, United States, 80228
      • Red Rocks OB/GYN / ID # 732
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Dr. David I. Lubetkin, LLC / ID # 703
    • Miami, Florida, United States, 33135
      • Coral Way Research / ID # 799
    • Miami, Florida, United States, 33155
      • La Salud Research Clinic, Inc. / ID # 824
    • 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
  • Illinois
    • Evergreen Park, Illinois, United States, 60805
      • Providea Health Partners LLC / ID # 734
  • Michigan
    • Flint, Michigan, United States, 48532
      • Onyx Clinical Research / ID # 793
    • Saginaw, Michigan, United States, 48602
      • Valley OBGYN / ID # 704
  • Ohio
    • Columbus, Ohio, United States, 43213
      • ClinOhio Res Services, LLC / ID # 722
    • Columbus, Ohio, United States, 43213
      • Complete Healthcare for Women / ID # 801
    • Franklin, Ohio, United States, 45005
      • Hilltop OBGYN / ID # 711
  • Tennessee
    • 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, 78758
      • OB/GYN North Austin / ID # 764
    • Dallas, Texas, United States, 75231
      • HCWC dba DiscoveryClinical Trials / ID # 771
    • Fort Worth, Texas, United States, 76104
      • Signature Gyn Services / ID # 726
    • Katy, Texas, United States, 77450
      • Medical Colleagues of Texas / ID # 819
    • League City, Texas, United States, 77573
      • Maximos OB/GYN
  • Utah
    • Draper, Utah, United States, 84020
      • Physicians Research Options / ID # 766

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

The subject must have:

• completed the 6-month treatment in the main study
• agreed to continue to use only the analgesic rescue medication permitted by the protocol during the Treatment and Follow-up Periods
• agreed to continue to comply with the requirements of the study protocol for the duration of the extension study

Exclusion Criteria:

The subject will be excluded if she:

• is pregnant or breast feeding or is planning a pregnancy within the duration of the of the study (including the Follow-up Period)
• likely to require treatment during the study with any of the restricted medications
• has any other clinically significant gynecologic condition identified during the main study on transvaginal ultrasound (TVUS), on endometrial biopsy or at the manual breast examination, which might interfere with the study efficacy and safety objectives
• meets any of the main study discontinuation criteria

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 12 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 12
Non-menstrual pelvic pain	Change at Month 12 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 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dysmenorrhea	Change from baseline to Month 12 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 12
Non-menstrual pelvic pain	Change from baseline to Month 12 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 12
Dyschezia	Change from baseline to Month 12 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 12
Overall Pelvic Pain	Change from baseline to Month 12 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 12
Interference of pain with the ability to perform daily activities	Change from baseline to Month 12 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 12
Dyspareunia	Change from baseline to Month 12 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 12
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 each scheduled assessment	During the preceding 4-week period at each scheduled assessment
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 each scheduled assessment	During the preceding 4-week period at each scheduled assessment

Collaborators and Investigators

• Sponsor: Kissei Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2020
• Primary Completion (Actual): January 8, 2021
• Study Completion (Actual): February 16, 2021

Study Registration Dates

• First Submitted: April 29, 2020
• First Submitted That Met QC Criteria: April 29, 2020
• First Posted (Actual): May 1, 2020

Study Record Updates

• Last Update Posted (Estimate): January 13, 2023
• Last Update Submitted That Met QC Criteria: January 12, 2023
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Dysmenorrhea; Dyschezia; Dyspareunia; Non-menstrual pelvic pain
• Additional Relevant MeSH Terms: Endometriosis
• Other Study ID Numbers: 19-OBE2109-005

Drug and device information, study documents

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