A Phase 3 Study to Confirm the Efficacy and Safety of Linzagolix to Treat Endometriosis-associated Pain

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Endometriosis

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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 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: Add-back capsule (E2 1 mg / NETA 0.5 mg)<br>* For oral administration once daily<br>Drug: Placebo tablet to match 75 mg linzagolix tablet<br>* For oral administration once daily<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo tablet to match 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>|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| 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 Verbal Rating Scale (VRS) 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 | 
| 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 | 

 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