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

Phase 2

Completed

Conditions: Endometriosis

Interventions: Drug: Quinagolide 1080 µg
Drug: Placebo

Registration Number: NCT03749109

Lead Sponsor: Ferring Pharmaceuticals

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 67

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Quinagolide 1080 µg	Quinagolide 1080 µg	Vaginal ring containing Quinagolide 1080 µg, with daily target release rate of 13.5 µg.
Placebo	Placebo	Vaginal ring containing matching placebo

Primary Outcome Measures

Name	Time	Method
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	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	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.

Secondary Outcome Measures

Name	Time	Method
Proportion of Subjects With a Lesion of Any Type Decreased in a Size of ≥5 mm on MR Images at Cycle 4	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	The MRI examination was performed on a high resolution 3T machine at screening and at end-of-treatment / cycle 4.
Number of New or Disappearing Endometrioma, DIE and Adenomyosis Lesions Summed by Type on MR Images at Cycle 4	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	The MRI examination was performed on a high resolution 3T machine at screening and at end-of-treatment / cycle 4.
Changes in the Mean Individual and Total Symptom and Sign Severity of Scores of the Biberoglu and Behrman (B&B) Scale at Cycle 4	At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)	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.
Changes in the Volumes (mm3) of Endometrioma and DIE Lesions Summed by Type on MR Images at Cycle 4	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	The MRI examination was performed on a high resolution 3T machine at screening and at end-of-treatment / cycle 4.
Changes in the Sizes of Endometrioma Assessed by Transvaginal Ultrasound (TVU) at Cycle 4	At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)	Transvaginal ultrasound (TVU) will be performed, preferably by the same sonographer, at the screening visit and at end-of-treatment / cycle 4.
Proportion of Lesions by Type With a Decrease in a Size of ≥5 mm on MR Images at Cycle 4	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	The MRI examination was performed on a high resolution 3T machine at screening and at end-of-treatment / cycle 4.
Percentage of Changes in the Sizes of Endometrioma, DIE and Adenomyosis Lesions Summed by Type on MR Images at Cycle 4	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	The MRI examination was performed on a high resolution 3T machine at screening and at end-of-treatment / cycle 4.
Changes in the Numerical Rating Scale (NRS) Pain Scores Per Cycle at Cycles 1, 2, 3 and 4	At baseline and at menstrual cycles 1 (~1 month), 2 (~2 months), 3 (~3 months) and 4 (~4 months)	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
Changes in the Endometriosis Health Profile-30 (EHP-30) Scores at Cycles 2 and 4	At baseline, at menstrual cycles 2 (~2 months) and 4 (~4 months)	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.
Changes in the Menstrual Bleeding Pattern Over 4 Cycles (Menstrual Cycle Duration)	At baseline and at menstrual cycles 1 (~1 month), 2 (~2 months), 3 (~3 months) and 4 (~4 months)	Assessed by subject self-reported answers to menstrual bleeding questions. The Menstrual Cycle Duration is shown.
Plasma Concentrations of Quinagolide and Its Metabolites During Cycles 1 to 4	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)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Hemaglobin	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Ery. Mean Corpuscular Hemoglobin	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Ery. Mean Corpuscular Volume	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Bilirubin	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Lactate Dehydrogenase	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in the Menstrual Bleeding Pattern Over 4 Cycles (Menstrual Bleeding Duration)	At baseline and at menstrual cycles 1 (~1 month), 2 (~2 months), 3 (~3 months) and 4 (~4 months)	Assessed by subject self-reported answers to menstrual bleeding questions. The Menstrual Bleeding Duration is shown.
Serum Levels of Prolactin During Cycle 1, at Cycles 2 and 4	Within 1-5 days post randomization, and at menstrual cycles 2 (~2 months) and 4 (~4 months)	Assessed by blood sample collection
Serum Levels of Thyroid-stimulating Hormone (TSH) During Cycle 1, at Cycles 2 and 4	Within 1-5 days post randomization, and at menstrual cycles 2 (~2 months) and 4 (~4 months)	Assessed by blood sample collection
Serum Levels of Insulin-like Growth Factor-1 (IGF-1) During Cycle 1, at Cycles 2 and 4	Within 1-5 days post randomization, and at menstrual cycles 2 (~2 months) and 4 (~4 months)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Hematocrit	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Ery. Mean Corpuscular HGB Concentration	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Erythrocytes	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Leukocytes	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Alanine Aminotransferase	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Alkaline Phosphatase	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Aspartate Aminotransferase	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Calcium	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Platelets	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Albumin	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Bicarbonate	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Direct Bilirubin	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Cholesterol	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Creatinine	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Chloride	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Glucose	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Phosphate	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Protein	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Urate	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Frequency and Intensity of Adverse Events	From obtaining the informed consent to end of trial (up to 6 menstrual cycles ~ around 6 months, each cycle is approximately 28 days)	Assessed by and Adverse Event Log completed by the Investigator
Changes in Clinical Chemistry and Hematology Parameters: Gamma Glutamyl Transferase	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Potassium	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Sodium	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Changes in Clinical Chemistry and Hematology Parameters: Urea Nitrogen	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection
Proportion of Subjects With Markedly Abnormal Changes in Clinical Chemistry and Hematology Parameters	At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)	Assessed by blood sample collection

Trial Locations

Locations (11): Gyneacology Rigshospitalet
🇩🇰
Copenhagen, Denmark
Gabinet Lekarski Specjalistyczny SONUS
🇵🇱
Warsaw, Poland
Specjalistyczny Gabinet Lekarski
🇵🇱
Warsaw, Poland
Centrum Medyczne PROMED
🇵🇱
Kraków, Poland
Azienda Opsedaliera Universitaria Careggi
🇮🇹
Florence, Italy
Università degli Studi di Roma La Sapienza
🇮🇹
Rome, Italy
Universitätsklinikum Carl Gustav Carus
🇩🇪
Dresden, Germany
Universitätsklinikum Münster
🇩🇪
Münster, Germany
Charité Universitätsmedizin
🇩🇪
Berlin, Germany
Azienda Ospedaliera Universitaria Integrata Verona
🇮🇹
Verona, Italy
Azienda Ospedaliera Universitaria Senese
🇮🇹
Siena, Italy