Uterine Fibroids MedDRA version: 18.0 Level: LLT Classification code 10046784 Term: Uterine fibroids System Organ Class: 100000004864
Conditions
Sponsors
Euroscreen S.A
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Has been diagnosed with uterine fibroids and never received surgical treatment for a myoma; 2) Is a pre-menopausal woman between 18 and 50 years inclusive at screening; 3) Has a clinical breast examination without clinically relevant findings at the screening visit; 4) Has a myomatous uterus with a size equivalent to a uterus of =16 weeks gestation and at least one measurable noncalcified fibroid =3 cm diameter but none ?10 cm diameter as measured by TVU (the three largest myoma's are to be followed up); 5) Willing to undergo an endometrial biopsy at Visit 2 and at Week 12 (end-of-treatment); Has been diagnosed with menorrhagia (PBAC >100 during the first 8 days of the menses); otherwise having a regular menstrual cycle (21-36 days); 7) Body Mass Index (BMI) between 18 – 33 kg/m² inclusive; 8) Has a negative (normal or atypical squamous cell of uncertain significance) cervical smear (Papanikolaou test [PAP], cytobrush or equivalent) within 36 months prior to screening; 9) In good physical and mental health as determined on the basis of medical history and general physical examination performed at screening; 10) Hematology and chemistry parameters, heart rate (HR) and/or blood pressure, and electrocardiogram ECG within the reference range for the population studies, or showing no clinically relevant deviations, as judged by the investigator; 11) Negative urine test for selected drugs (amphetamines benzodiazepines, cannabinoids, cocaine, tetrahydrocannabinol, barbiturates or opiates) of abuse at screening and before first administration of study drug; 12) Has a negative pregnancy test at screening; Note: pregnancy testing will consist of a serum pregnancy test at screening and urine pregnancy tests at other visits. 13) Females who are not breast-feeding; 14) Women of childbearing potential agrees not to get pregnant and willing to be abstinent or to use adequate highly effective contraception (failure rate less than 1% per year) during the trial and for at least 42 days after end of treatment; The following non-hormonal contraceptive methods are defined as acceptable: o Partner with a vasectomy performed at least 3 months prior to the study and with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate. (The vasectomized male partner should be the sole partner for that subject). o True abstinence: When this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptom-thermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception) o The subject is homosexual/has no intercourse with the opposite sex o Partner is using condoms in combination with spermicidal cream or gel Women of childbearing potential are defined as any female who has experienced menarche and are not post-menopausal or permanently sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy); 15) Informed Consent Form (ICF) signed voluntarily before any study-related procedure is performed, indicating that the subject understands the purpose of and procedures required for the study and is willing to participate in the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 24 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Has a hemoglobin value 30 mIU/mL at screening; 3) Has a history of or currently ongoing hemoglobinopathy (i.e. Sickle Cell anemia and Thalassemia) or coagulopathies; 4) Has a known history of severe hypersensitivity or severe allergy to sanitary goods; 5) Has a history of uterine surgery (except Caesarean section or cervical conization) or bilateral oophorectomy; 6) Has a history of a previous endometrial ablation or uterine artery embolization; 7) Judged by investigator to have marked abnormal uterine bleeding; or non-diagnosable abnormal genital bleeding; or anovulatory bleeding; 8) Has regular abdominal discomfort or pain due to gastro-intestinal, urological or gynecological conditions other than UF; 9) Has a history of or currently ongoing pelvic inflammatory disease; 10) Has a history of or currently ongoing malignant tumor (except for basal cell carcinoma of the skin that has been treated with no evidence or recurrence); 11) Has been treated within 3 months of screening with any of the following drugs: gonadotrophin releasing hormone (GnRH) agonist/antagonist, selective estrogen receptor modulator (SERM), selective progesterone receptor modulator (SPRM), dienogest, danazol aromatase inhibitor, anticoagulant drugs, antiplatelet drug, glucocorticoids, mineralocorticoids, androgens, depot contraceptive preparations or vitamin K; 12) Treatment with hormonal contraceptives (oral, transdermal, coated intrauterine device) and/or tranexamic acid should be stopped 1 month prior to screening; 13) Has a known severe allergy, hypersensitivity, or intolerance to any drug, including the study drug and any of its excipients; 14) Judged by investigator to be inappropriate to participate in this study based on findings observed during the general physical/gynecological examination (including endometrial hyperplasia on the biopsy of Visit 2); or clinically relevant findings on the 12-lead ECG; 15) Has a contraindication for undergoing an MRI scan (e.g., unsuitable body weight, claustrophobia, pacemaker, …); 16) Has active liver disease or jaundice, or with out-of-range values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST); or total bilirubin >1.3 times the upper limit of normal (ULN); or creatinine >1.25 times the ULN at screening; 17) Has a medical condition or chronic disease (including neurological [including cognitive], hepatic, renal, cardiovascular, gastrointestinal, pulmonary, or endocrine disease), or malignancy that could confound interpretation of the study outcome as judged by the investigator; 18) Has any psychological disorder according to criteria indicated in the Diagnostics and Statistical Manual of Mental Disorders, 4th edition within one year before screening. Such disorders include, but are not limited to, alcohol (more than 3 glasses of wine, beer, or equivalent/day) and substance abuse/dependence within 2 years prior to the initial study medication administration; 19) Has a history of poor compliance in clinical research studies; 20) Has a positive hepatitis panel (including hepatitis B surface antigen [HBsAg] or anti-hepatitis C virus [HCV] antibodies) or positive human immunodeficiency virus (HIV) antibody at screening; 21) Presence or sequelae of gastrointestinal, liver, kidney or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs, as judged by the i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate efficacy of two doses of ESN364 versus placebo when administered for 12 weeks to reduce excessive uterine bleeding (assessed by Pictorial Blood Loss Assessment Chart [PBAC]).;Secondary Objective: at Week 4 and Week 8 (assessed by PBAC) • To evaluate efficacy of two doses of ESN364 versus placebo when administered for 12 weeks to reduce total fibroid volume (assessed by Magnetic Resonance Imaging [MRI] and/or Transvaginal Ultrasound [TVU]) • To evaluate if two doses of ESN364 versus placebo will lead to amenorrhea in Week 4, Week 8, and Week 12 (assessed by PBAC) • To evaluate efficacy of two doses of ESN364 versus placebo when administered for 12 weeks to decrease uterine volume (assessed by MRI and/or TVU) • To evaluate efficacy of two doses of ESN364 versus placebo when administered for 12 weeks to improve pain and quality of life (assed by Visual Analogue Scale [VAS] for dysmenorrhea, pelvic pain, urinary symptoms, bloating, and abdominal pressure, by the Uterine Fibroid Symptom - Quality of Life [UFS-QoL] score, and by the Patients’ Global Impression of Change [PGIC] scale) For further information on the objectives, please see protocol;Primary end point(s): Decrease in uterine bleeding as change from baseline to Week 12. Blood loss will be assessed using the PBAC;Timepoint(s) of evaluation of this end point: during the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Decrease in uterine bleeding as change from baseline to Week 4 and Week 8 assessed by PBAC • Percentage of subjects in amenorrhea at Week 4, Week 8, and Week 12 (end-of-treatment) assessed by PBAC • Change in total fibroid volume of the three largest fibroids assessed by MRI from baseline to end-of-treatment visit (Week 12) • Change in total fibroid volume assessed by TVU from baseline to end-of-treatment visit (Week 12) • Change in total uterine volume assessed by MRI and/or TVU from baseline to end-of-treatment visit (Week 12) • Change from baseline in symptoms related to uterine fibroids (measurement of discomfort due to uterine fibroids using VAS scales, the UFS-QoL, and the PGIC scale) at Week 4, Week 8, and Week 12 (end-of-treatment) • Change in hemoglobin and hematocrit levels from baseline to end-of-treatment visit (Week 12);Timepoint(s) of evaluation of this end point: during the trial | — |
Countries
Austria, Belgium, Germany
Contacts
Public ContactSteven Ramael
Euroscreen S.A
Outcome results
None listed