Clinical trial NCT03749109: Quinagolide Vaginal Ring on Lesion Reduction Assessed by MRI in Women With Endometriosis/Adenomyosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Endometriosis
Keywords: Endometrioma
Adenomyosis
Deep infiltrating endometriosis
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-11-21
Enrollment: 67
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: 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
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
Secondary outcomes:
measure: Percentage of Changes in the Sizes of Endometrioma, DIE and Adenomyosis Lesions Summed by Type on MR Images at Cycle 4
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Proportion of Lesions by Type With a Decrease in a Size of ≥5 mm on MR Images at Cycle 4
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Proportion of Subjects With a Lesion of Any Type Decreased in a Size of ≥5 mm on MR Images at Cycle 4
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Number of New or Disappearing Endometrioma, DIE and Adenomyosis Lesions Summed by Type on MR Images at Cycle 4
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in the Volumes (mm3) of Endometrioma and DIE Lesions Summed by Type on MR Images at Cycle 4
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in the Sizes of Endometrioma Assessed by Transvaginal Ultrasound (TVU) at Cycle 4
timeFrame: At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in the Mean Individual and Total Symptom and Sign Severity of Scores of the Biberoglu and Behrman (B&B) Scale at Cycle 4
timeFrame: At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in the Numerical Rating Scale (NRS) Pain Scores Per Cycle at Cycles 1, 2, 3 and 4
timeFrame: At baseline and at menstrual cycles 1 (~1 month), 2 (~2 months), 3 (~3 months) and 4 (~4 months)
measure: Changes in the Endometriosis Health Profile-30 (EHP-30) Scores at Cycles 2 and 4
timeFrame: At baseline, at menstrual cycles 2 (~2 months) and 4 (~4 months)
measure: Changes in the Menstrual Bleeding Pattern Over 4 Cycles (Menstrual Cycle Duration)
timeFrame: At baseline and at menstrual cycles 1 (~1 month), 2 (~2 months), 3 (~3 months) and 4 (~4 months)
measure: Changes in the Menstrual Bleeding Pattern Over 4 Cycles (Menstrual Bleeding Duration)
timeFrame: At baseline and at menstrual cycles 1 (~1 month), 2 (~2 months), 3 (~3 months) and 4 (~4 months)
measure: Serum Levels of Prolactin During Cycle 1, at Cycles 2 and 4
timeFrame: Within 1-5 days post randomization, and at menstrual cycles 2 (~2 months) and 4 (~4 months)
measure: Serum Levels of Thyroid-stimulating Hormone (TSH) During Cycle 1, at Cycles 2 and 4
timeFrame: Within 1-5 days post randomization, and at menstrual cycles 2 (~2 months) and 4 (~4 months)
measure: Serum Levels of Insulin-like Growth Factor-1 (IGF-1) During Cycle 1, at Cycles 2 and 4
timeFrame: Within 1-5 days post randomization, and at menstrual cycles 2 (~2 months) and 4 (~4 months)
measure: Plasma Concentrations of Quinagolide and Its Metabolites During Cycles 1 to 4
timeFrame: 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)
measure: Changes in Clinical Chemistry and Hematology Parameters: Hematocrit
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Hemaglobin
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Ery. Mean Corpuscular Hemoglobin
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Ery. Mean Corpuscular HGB Concentration
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Ery. Mean Corpuscular Volume
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Platelets
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Erythrocytes
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Leukocytes
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Alanine Aminotransferase
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Albumin
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Alkaline Phosphatase
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Aspartate Aminotransferase
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Bicarbonate
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Direct Bilirubin
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Bilirubin
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Calcium
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Chloride
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Cholesterol
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Creatinine
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Gamma Glutamyl Transferase
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Glucose
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Lactate Dehydrogenase
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Phosphate
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Potassium
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Sodium
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Protein
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Urate
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Changes in Clinical Chemistry and Hematology Parameters: Urea Nitrogen
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Proportion of Subjects With Markedly Abnormal Changes in Clinical Chemistry and Hematology Parameters
timeFrame: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)
measure: Frequency and Intensity of Adverse Events
timeFrame: From obtaining the informed consent to end of trial (up to 6 menstrual cycles ~ around 6 months, each cycle is approximately 28 days)
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Gyneacology Rigshospitalet
city: Berlin
country: Germany
facility: Charité Universitätsmedizin
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Florence
country: Italy
facility: Azienda Opsedaliera Universitaria Careggi
city: Rome
country: Italy
facility: Università degli Studi di Roma La Sapienza
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona
city: Kraków
country: Poland
facility: Centrum Medyczne PROMED
city: Warsaw
country: Poland
facility: Gabinet Lekarski Specjalistyczny SONUS
city: Warsaw
country: Poland
facility: Specjalistyczny Gabinet Lekarski
Study officials:
affiliation: Ferring Pharmaceuticals
name: Global Clinical Compliance
role: STUDY_DIRECTOR
References: