Overview

Surgical Myomectomy Followed by Oral Myfembree Versus Standard of Care Trial (SOUL)

Status:
Not yet recruiting
Trial end date:
2026-04-01
Target enrollment:
0
Participant gender:
Female
Summary
In this project, the proposition is that the use of daily dosed Myfembree ( a combination of relugolix with estradiol and norethindrone acetate), FDA-approved medication to treat heavy menses fibroid-related symptoms, has the potential to delay the recurrence of fibroid symptoms, prolong the improved quality of life and delay the need for re-intervention after uterine sparing surgery versus the routine standard of care.
Phase:
Phase 4
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
University of Chicago
Collaborator:
Myovant Sciences GmbH
Criteria
Inclusion Criteria:

- Inclusion Criteria (all inclusion criteria must have been met prior to randomization
unless otherwise specified):

1. Has voluntarily signed and dated the informed consent form prior to initiation of
any screening or study-specific procedures

2. Premenopausal female aged 18 years and older on the day of signing of the
informed consent form

3. Has a diagnosis of uterine fibroids that is confirmed by a pelvic ultrasound
(transvaginal and/or transabdominal) performed during the screening period.

4. Has at least one or more of the following symptoms:

1. Heavy menses defined as PBAC (Pictorial Bleeding Assessment Chart) score ≥
120

2. Pelvic pain during menses measured on NRS (Numeric Pain Rating Scale) ≥ 4 at
baseline

3. Moderately severe fibroid-related symptoms (a score ≥ 25 on the Uterine
Fibroid UF quality of life symptoms severity subscale)

5. Has a negative urine pregnancy test at the Screening, Baseline and interval
clinic visits

6. Agrees to use two forms of non-hormonal contraception (dual contraception)
consistently during the screening period and the randomized treatment period.
These may include: Diaphragm, cervical cap, spermicides, male and female condoms,
copper IUD ( intra uterine device) and sponge. Each one will be explained in
detail for the participants. However, the patient is not required to use dual
contraception if she:

1. Has a sexual partner(s) who was vasectomized at least 6 months prior to the
screening period.

2. Had a bilateral tubal occlusion (including ligation and blockage methods
such as Essure™), at least 4 months prior to the first screening visit
(patients with Essure™ must have prior confirmation of tubal occlusion by
hysterosalpingogram);

3. Is not sexually active with men; periodic sexual relationship(s) with men
requires the use of dual non-hormonal contraception as noted above; or

4. Practices total abstinence from sexual intercourse as her preferred
lifestyle; periodic abstinence is not acceptable.

7. Has an endometrial (aspiration) biopsy, if clinically indicated, performed during
the screening period, with results showing no clinically significant endometrial
pathology (hyperplasia, endometritis, or endometrial cancer).

8. If ≥ 40 years of age at the time of the Baseline Day 1 visit, has a normal
mammogram (Breast Imaging Reporting and Data System category 1 to 3 or
equivalent) during the screening period or within 12 months prior to the
screening period.

Exclusion Criteria:

1. Has transvaginal and/or transabdominal ultrasound during the screening period
demonstrating pathology other than uterine fibroids that could be responsible for or
contributing to the patient's heavy menstrual bleeding, such as uterine or cervical
polyps >1.0 cm, large simple ovarian cyst >4.0 cm, endometrioma(s), or any other
clinically significant gynecological disorder determined by the investigator to
require further evaluation and/or treatment.

Note: Saline or gel contrast is not routinely required. Use of such contrast is
required only when the endometrium cannot be evaluated or when there are ambiguous and
potentially exclusionary findings on the transvaginal and/or transabdominal ultrasound
(e.g., suspected intrauterine masses, equivocal endometrial findings, etc.)

2. Has unexplained vaginal bleeding outside of the patient's regular menstrual cycle

3. Has undergone ultrasound-guided laparoscopic radiofrequency ablation, or any other
surgical procedure for fibroids, uterine artery embolization, magnetic
resonance-guided focused ultrasound for fibroids, as well as endometrial ablation for
abnormal uterine bleeding within 6 months prior to the Screening visit

4. Has visually confirmed endometriosis diagnosis: detection of endometriotic lesions
during laparoscopy or laparotomy (with or without pathological diagnosis) within the
past 10 years.

5. Has a history of or currently has osteoporosis, or other metabolic bone disease,
hyperparathyroidism, hyperprolactinemia, hyperthyroidism, anorexia nervosa, or low
traumatic (from the standing position) or atraumatic fracture (toe, finger, skull,
face, and ankle fractures are allowed). A history of successfully treated
hyperparathyroidism, hyperprolactinemia, or hyperthyroidism is allowed if the
patient's bone mineral density is within normal limits

6. Has a history of the use of bisphosphonates, calcitonin, calcitriol, ipriflavone,
teriparatide, denosumab, or any medication other than calcium and vitamin D
preparations to treat bone mineral density loss

7. Anticipated use of systemic glucocorticoids at an oral prednisone-equivalent dose of
more than 5 mg every other day during the study. Note: topical, inhaled, intranasal,
optic, ophthalmic, intraarticular, or intralesional subcutaneous are permitted without
restriction

8. Gastrointestinal disorder affecting absorption or gastrointestinal motility

9. Has any additional contraindication to treatment with low-dose estradiol and
norethindrone acetate, including:

1. Current, known, suspected, or history of breast cancer

2. Current, known, or suspected hormone -dependent neoplasia

3. High risk of arterial, venous thrombotic disorder or thromboembolic disorder

i. women over 35 years of age who smoke or women with uncontrolled hypertension

d. Active thrombotic or thromboembolic disease or history of these conditions prior to
the Baseline Day 1 visit or risk factors for such conditions. These conditions
include: i. deep vein thrombosis ii. pulmonary embolism iii. vascular disease (e.g.,
cerebrovascular disease, coronary artery disease, peripheral vascular disease) iv.
inherited or acquired hypercoagulopathies, known protein C, protein S, or antithrombin
deficiency, or other known thrombophilia disorders, including Factor V Leiden
thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example,
subacute bacterial endocarditis with valvular disease, or atrial fibrillation) v.
uncontrolled hypertension vi. headaches with focal neurological symptoms or migraine
headaches with aura if over 35 years of age vii. Women at increased risks for
thrombotic or thromboembolic events

e. Known anaphylactic reaction or angioedema or hypersensitivity to estradiol or
norethindrone acetate

f. Currently pregnant or lactating, or intends to become pregnant or to donate ova
during the study period or within 1 month after the end of the study

10. Has jaundice or known current active liver disease from any cause, including hepatitis
A (HAV IgM), hepatitis B (HBsAg), or hepatitis C (HCV Ab positive, confirmed by HCV
RNA);

11. Has any of the following cervical pathology: high grade cervical neoplasia, atypical
glandular cells, atypical endocervical cells, atypical squamous cells favoring high
grade. Of note, patients with atypical squamous cells of undetermined significance and
low-grade cervical neoplasia may be included in the study if high risk human papilloma
virus testing is negative or if DNA testing for human papilloma virus 16 and 18 DNA
testing is negative

12. Has any of the following clinical laboratory abnormalities indicating hepatic or
gallbladder impairment:

1. Alanine aminotransferase or aspartate aminotransferase > 2.0 times the upper
limit of normal (ULN), or bilirubin (total bilirubin) > 1.5 x ULN on clinical
laboratory testing at either the Screening 1 or Screening 2 visit (or > 2.0 x ULN
if secondary to Gilbert syndrome or pattern consistent with Gilbert syndrome);

2. Estimated glomerular filtration rate < 60 mL/min/m2 using the Modification of
Diet in Renal Disease method

13. Has clinically significant cardiovascular disease including:

1. Prior history of myocardial infarction

2. History of angina

3. History of congestive heart failure

4. History of clinically significant ventricular arrhythmias such as ventricular
tachycardia, ventricular fibrillation, or torsade de pointes, or Mobitz II second
degree or third-degree heart block without a permanent pacemaker in place or
untreated supraventricular tachycardia (heart rate ≥ 120 beats per minute)

5. QT interval by the Fridericia correction formula (QTcF) of > 470 msec

6. Hypotension, as indicated by systolic blood pressure < 84 millimeters of mercury
(mmHg) on 2 repeat measures at least 15 minutes apart or treated ongoing
symptomatic orthostatic hypotension with > 20 mmHg decrease in systolic blood
pressure one minute or more after assuming an upright position.

7. Uncontrolled hypertension, as indicated by systolic blood pressure > 160 mmHg on
2 repeat measures at least 15 minutes apart or diastolic blood pressure > 100
mmHg at any screening visit or the Baseline Day 1 visit.

8. Bradycardia as indicated by a heart rate of < 45 beats per minute on the
screening electrocardiogram.

14. Has been a participant in an investigational drug or device study within the 1 month
prior to Screening visit.

15. Has a history of clinically significant condition(s) including, but not limited to:

1. Untreated thyroid dysfunction or palpable thyroid abnormality (patients with
adequately treated hypothyroidism who are stable on medication are not excluded).

2. History of malignancy within the past 5 years or ongoing malignancy other than
curatively treated nonmelanoma skin cancer or surgically cured Stage 0 in situ
melanoma

16. Any current psychiatric disorder that would, in the opinion of the investigator or
medical monitor, impair the ability of the patient to participate in the study or
would impair interpretation of their data. Patients with major depression,
post-traumatic stress disorder, bipolar disorder, schizophrenia, or other psychotic
disorders, based on Diagnostic and Statistical Manual of Mental Disorders-5 criteria
who have been unstable based on the investigator's or mental health professional's
judgement or whose psychiatric drug regimen has changed during the 3 months prior to
Screening or is expected to change during the study should not be enrolled. Has a
contraindication or history of sensitivity to any of the study treatments or
components thereof; or has a history of drug or other allergy that, in the opinion of
the investigator or medical monitor, contraindicates study participation

17. Has a prior (within 1 year of Screening 1 visit) or current history of drug or alcohol
abuse disorder according to Diagnostic and Statistical Manual of Mental Disorders V
(all patients must be questioned about their drug and alcohol use, and this should be
documented in the electronic case report form)

18. Has participated in a previous clinical study that included the use of Relugolix or
has received this treatment within 3 months of the study.

19. Is an immediate family member, study site employee, or is in a dependent relationship
with a study site employee who is involved in the conduct of this study (e.g., spouse,
parent, child, or sibling)

20. Is inappropriate for participation in this study for other reasons, as determined by
the investigator, sub-investigator, or medical monitor.