Extension to Study on Efficacy and Safety of Linzagolix for the Treatment of Endometriosis-associated Pain (EDELWEISS 6)

Study Overview
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Brief Summary
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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.

Detailed Description
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This is a prospective, randomized, double-blind study. Subjects who have completed the 6-month Treatment Period in 18-OBE2109-003 - Edelweiss 3 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.

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

Conditions
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Endometriosis

Intervention / Treatment
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* Drug: 75 mg linzagolix tablet
* Drug: 200 mg linzagolix tablet
* Drug: Placebo tablet to match 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 capsule to match Add-back capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject must have: completed the 6-month treatment in the main study. agree to continue to use only the analgesic rescue medication permitted by the protocol during the Treatment and Follow-up Periods. 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. met any of the main study discontinuation criteria

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dysmenorrhea, Dyspareunia, Dyschezia, Non-menstrual pelvic pain