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

Ferring Pharmaceuticals67 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Endometriosis

Interventions

Quinagolide 1080 µgDRUG

Vaginal ring containing Quinagolide 1080 µg for daily releases

PlaceboDRUG

Matching placebo

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 45 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Pre-menopausal women between the ages 18-45 years (both inclusive) at the time of signing the informed consent 2. Body mass index (BMI) of 18-35 kg/m2 (both inclusive) at screening 3. Confirmation of deep infiltrating endometriosis (DIE), endometrioma or adenomyosis by high-resolution MRI at screening 4. 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 5. 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) 6. 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: 1. Use of depot medroxyprogesterone acetate (MPA) within 10 months prior to the screening visit. 2. Use of gonadotropin-releasing (GnRH) agonists (3-month depot) or dopamine agonists within 6 months prior to the screening visit. 3. 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. 4. Use of hormonal contraceptives (including combined oral contraceptive pill, transdermal patch, and contraceptive ring) within 1 menstrual cycle prior to the screening visit. 5. Contraindications to MRI such as having internal/external metallic devices and/or accessories (e.g. cardiac pacemakers and leg braces)

Locations (11)

Gyneacology Rigshospitalet

Copenhagen, Denmark

Charité Universitätsmedizin

Berlin, Germany

Universitätsklinikum Carl Gustav Carus

Dresden, Germany

Universitätsklinikum Münster

Outcomes

Primary Outcomes

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.

Time frame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)

Data from ClinicalTrials.gov

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Azienda Opsedaliera Universitaria Careggi

Florence, Italy

Università degli Studi di Roma La Sapienza

Rome, Italy

Azienda Ospedaliera Universitaria Senese

Siena, Italy

Azienda Ospedaliera Universitaria Integrata Verona

Verona, Italy

Centrum Medyczne PROMED

Krakow, Poland

Gabinet Lekarski Specjalistyczny SONUS

Warsaw, Poland

...and 1 more locations

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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: From obtaining the informed consent to end of trial (up to 6 menstrual cycles ~ around 6 months, each cycle is approximately 28 days)