Quinagolide Vaginal Ring on Lesion Reduction Assessed by MRI in Women With Endometriosis/Adenomyosis

Study Overview
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Brief Summary
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This will be a randomized, double-blind, placebo-controlled, proof-of-mechanism phase 2 trial investigating the effect of quinagolide extended-release vaginal ring on reduction of lesions assessed by high-resolution magnetic resonance imaging in women with endometrioma, deep infiltrating endometriosis, and/or adenomyosis.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Proof-of-mechanism Phase 2 Trial Investigating the Effect of Quinagolide Extended-release Vaginal Ring on Reduction of Lesions Assessed by High-resolution Magnetic Resonance Imaging in Women With Endometrioma, Deep Infiltrating Endometriosis, and/or Adenomyosis

Conditions
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Endometriosis

Intervention / Treatment
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* Drug: Quinagolide 1080 µg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-menopausal women between the ages 18-45 years (both inclusive) at the time of signing the informed consent Body mass index (BMI) of 18-35 kg/m2 (both inclusive) at screening Confirmation of deep infiltrating endometriosis (DIE), endometrioma or adenomyosis by high-resolution MRI at screening Transvaginal ultrasound (TVU) documenting a uterus with no abnormalities of endometrium and presence of at least one ovary with no clinically significant abnormalities at screening. Note that presence of uterine fibroids are not exclusionary but presence of any submucosal fibroids or polyps are exclusionary Willing and able to use a non-hormonal single-barrier method (i.e. condom) for contraception from the start of screening to the end-of-treatment. This is not required if adequate contraception is achieved by vasectomy of the male sexual partner, surgical sterilisation (e.g. tubal ligation and blockage methods such as ESSURE) of the subject, or true abstinence of the subject (sporadic sexual intercourse with men requiring condom use) Willing to avoid the use of vaginal douches or any other intravaginally administered medications or devices (except for tampons) from randomization to the end of treatment Exclusion Criteria: Use of depot medroxyprogesterone acetate (MPA) within 10 months prior to the screening visit. Use of gonadotropin-releasing (GnRH) agonists (3-month depot) or dopamine agonists within 6 months prior to the screening visit. Use of GnRH agonists (1-month depot or nasal spray), GnRH antagonists, aromatase inhibitors, danazol, birth control implants (e.g. NEXPLANON), progestogen or levonorgestrel releasing intrauterine device (IUD) within 3 months prior to the screening visit. Use of hormonal contraceptives (including combined oral contraceptive pill, transdermal patch, and contraceptive ring) within 1 menstrual cycle prior to the screening visit. Contraindications to MRI such as having internal/external metallic devices and/or accessories (e.g. cardiac pacemakers and leg braces)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Quinagolide 1080 µg<br>Vaginal ring containing Quinagolide 1080 µg, with daily target release rate of 13.5 µg. | Drug: Quinagolide 1080 µg<br>* Vaginal ring containing Quinagolide 1080 µg for daily releases<br>* Other names: FE 999051;|
| Placebo Comparator: Placebo<br>Vaginal ring containing matching placebo | Drug: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the Sizes (mm) of Endometrioma, Deep Infiltrating Endometriosis (DIE) and Adenomyosis Lesions Summed by Type on Magnetic Resonance (MR) Images at Cycle 4 | The MRI examination was performed on a high resolution 3T machine at screening and at end-of-treatment / cycle 4. At screening, every measurable lesion (defined as ≥10 mm in size) of any type was recorded and was summed up by type for primary analysis. | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Changes in the Sizes of Endometrioma, DIE and Adenomyosis Lesions Summed by Type on MR Images at Cycle 4 | The MRI examination was performed on a high resolution 3T machine at screening and at end-of-treatment / cycle 4. | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Proportion of Lesions by Type With a Decrease in a Size of ≥5 mm on MR Images at Cycle 4 | The MRI examination was performed on a high resolution 3T machine at screening and at end-of-treatment / cycle 4. | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Proportion of Subjects With a Lesion of Any Type Decreased in a Size of ≥5 mm on MR Images at Cycle 4 | The MRI examination was performed on a high resolution 3T machine at screening and at end-of-treatment / cycle 4. | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Number of New or Disappearing Endometrioma, DIE and Adenomyosis Lesions Summed by Type on MR Images at Cycle 4 | The MRI examination was performed on a high resolution 3T machine at screening and at end-of-treatment / cycle 4. | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in the Volumes (mm3) of Endometrioma and DIE Lesions Summed by Type on MR Images at Cycle 4 | The MRI examination was performed on a high resolution 3T machine at screening and at end-of-treatment / cycle 4. | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in the Sizes of Endometrioma Assessed by Transvaginal Ultrasound (TVU) at Cycle 4 | Transvaginal ultrasound (TVU) will be performed, preferably by the same sonographer, at the screening visit and at end-of-treatment / cycle 4. | At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days) | 
| Changes in the Mean Individual and Total Symptom and Sign Severity of Scores of the Biberoglu and Behrman (B&B) Scale at Cycle 4 | B&B scale is a used scale for endometriosis that consists of two parts, with the first part evaluating symptoms (i.e. different types of pain) and the second part evaluating physical signs. In the first part, the subject was asked to grade her pelvic pain (item A), dysmenorrhea (item B) and dyspareunia (item C) during the last menstrual cycle as none, mild, moderate or severe, corresponding to a score of 0-3. In the second part, the investigator graded the subject's pelvic tenderness (item D) and induration (item E) based on findings from a pelvic examination as none, mild, moderate or severe, corresponding to a score of 0-3. The total symptom and sign severity score was the sum of all five scores, i.e. A+B+C+D+E. The score can be between 0 and 15. | At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days) | 
| Changes in the Numerical Rating Scale (NRS) Pain Scores Per Cycle at Cycles 1, 2, 3 and 4 | Assessed by Subjects. NRS is a 11-point scale, with 0 indicating no pain and 10 indicating the worst imaginable pain. Subjects were asked to score the worst pain in relation to endometriosis / adenomyosis on the NRS based on a recall of their experiences during the following timeframes: during the last menstrual cycle during the menstrual period of the last menstrual cycle during the non-menstrual period of the last menstrual cycle | At baseline and at menstrual cycles 1 ( 1 month), 2 ( 2 months), 3 ( 3 months) and 4 ( 4 months) | 
| Changes in the Endometriosis Health Profile-30 (EHP-30) Scores at Cycles 2 and 4 | EHP-30 is a quality-of-life questionnaire. Score ranges from 0-100 and lower score denotes improvement. It consists of 30 questions measuring the frequency of the endometriosis impact on their quality of life during the past four weeks, with five options of never, rarely, sometimes, often and always. | At baseline, at menstrual cycles 2 ( 2 months) and 4 ( 4 months) | 
| Changes in the Menstrual Bleeding Pattern Over 4 Cycles (Menstrual Cycle Duration) | Assessed by subject self-reported answers to menstrual bleeding questions. The Menstrual Cycle Duration is shown. | At baseline and at menstrual cycles 1 ( 1 month), 2 ( 2 months), 3 ( 3 months) and 4 ( 4 months) | 
| Changes in the Menstrual Bleeding Pattern Over 4 Cycles (Menstrual Bleeding Duration) | Assessed by subject self-reported answers to menstrual bleeding questions. The Menstrual Bleeding Duration is shown. | At baseline and at menstrual cycles 1 ( 1 month), 2 ( 2 months), 3 ( 3 months) and 4 ( 4 months) | 
| Serum Levels of Prolactin During Cycle 1, at Cycles 2 and 4 | Assessed by blood sample collection | Within 1-5 days post randomization, and at menstrual cycles 2 ( 2 months) and 4 ( 4 months) | 
| Serum Levels of Thyroid-stimulating Hormone (TSH) During Cycle 1, at Cycles 2 and 4 | Assessed by blood sample collection | Within 1-5 days post randomization, and at menstrual cycles 2 ( 2 months) and 4 ( 4 months) | 
| Serum Levels of Insulin-like Growth Factor-1 (IGF-1) During Cycle 1, at Cycles 2 and 4 | Assessed by blood sample collection | Within 1-5 days post randomization, and at menstrual cycles 2 ( 2 months) and 4 ( 4 months) | 
| Plasma Concentrations of Quinagolide and Its Metabolites During Cycles 1 to 4 | Assessed by blood sample collection | Within 1-5 days post randomization, within 7-14 days post randomization, and at menstrual cycles 1 ( 1 month), 2 ( 2 months), 3 ( 3 months) and 4 ( 4 months) | 
| Changes in Clinical Chemistry and Hematology Parameters: Hematocrit | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Hemaglobin | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Ery. Mean Corpuscular Hemoglobin | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Ery. Mean Corpuscular HGB Concentration | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Ery. Mean Corpuscular Volume | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Platelets | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Erythrocytes | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Leukocytes | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Alanine Aminotransferase | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Albumin | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Alkaline Phosphatase | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Aspartate Aminotransferase | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Bicarbonate | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Direct Bilirubin | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Bilirubin | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Calcium | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Chloride | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Cholesterol | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Creatinine | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Gamma Glutamyl Transferase | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Glucose | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Lactate Dehydrogenase | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Phosphate | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Potassium | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Sodium | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Protein | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Urate | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Changes in Clinical Chemistry and Hematology Parameters: Urea Nitrogen | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Proportion of Subjects With Markedly Abnormal Changes in Clinical Chemistry and Hematology Parameters | Assessed by blood sample collection | At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days) | 
| Frequency and Intensity of Adverse Events | Assessed by and Adverse Event Log completed by the Investigator | From obtaining the informed consent to end of trial (up to 6 menstrual cycles   around 6 months, each cycle is approximately 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endometrioma, Adenomyosis, Deep infiltrating endometriosis