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

NCT05538689 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: IRB22-0282
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Metrorrhagia; Pelvic Pain; Menorrhagia; Leiomyoma

Outcome Measures

Primary Outcomes (1)

• Fibroid recurrence on ultrasound after myomectomy.

  Fibroid recurrence when compared to the post-myomectomy baseline pelvic ultrasound (transvaginal and/or transabdominal), defined as a new fibroid identified on ultrasound with a volume \>1 cm3.

  36 months

Secondary Outcomes (6)

• Participants' quality of life assessed by the Quality of Life Questionnaire.

  36 months

• Work Productivity and Activity Impairment assessed by Work Productivity and Activity Impairment Questionnaire.

  36 months

• Female Sexual Function Impairment assessed by Female Sexual Function Index Questionnaire.

  36 months

• Heavy menses recurrence after myomectomy with score ≥ 120 on Pictorial Bleeding Assessment Chart (PBAC).

  36 months

• Pelvic pain recurrence after myomectomy with Numerical Rating Scale (NRS) ≥ 4 at baseline.

  36 months

Study Arms (3)

Study drug Myfembree

EXPERIMENTAL

Participants will be asked to take a once-daily tablet of Myfembree ( relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) for 24 months.

Drug: Myfembree Oral Product

Standard of Care

NO INTERVENTION

The standard of care will depend on the participant's type of surgery, health history, and clinical symptoms. It often includes pain management, bleeding management, physical exams, pelvic ultrasound, birth control, and Surgical reintervention.

Parallel group for participants who opt not to be randomized

OTHER

patients who do not consent to randomization or opt to be in a specific group will be included in a parallel observational study and be administered their preferred treatment.

Drug: Myfembree Oral Product

Interventions

Myfembree Oral Product DRUG

The study drug Myfembree will be taken orally with water, once daily, at approximately the same time, with or without food. Each tablet of Myfembree contains Relugolix 40mg, estradiol 1mg, and norethindrone acetate 0.5 mg.

Parallel group for participants who opt not to be randomized; Study drug Myfembree

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has voluntarily signed and dated the informed consent form prior to initiation of any screening or study-specific procedures
• Premenopausal female aged 18 years and older on the day of signing of the informed consent form
• Has a diagnosis of uterine fibroids that is confirmed by a pelvic ultrasound (transvaginal and/or transabdominal) performed during the screening period.
• Has at least one or more of the following symptoms:
• Heavy menses defined as PBAC (Pictorial Bleeding Assessment Chart) score ≥ 120
• Pelvic pain during menses measured on NRS (Numeric Pain Rating Scale) ≥ 4 at baseline
• Moderately severe fibroid-related symptoms (a score ≥ 25 on the Uterine Fibroid UF quality of life symptoms severity subscale)
• Has a negative urine pregnancy test at the Screening, Baseline and interval clinic visits
• Agrees to not be pregnant for at least 12 months. Participant may use any form of non-hormonal contraception consistently during the screening 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:
• Has a sexual partner(s) who was vasectomized at least 6 months prior to the screening period.
• 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);
• Is not sexually active with men; periodic sexual relationship(s) with men requires the use of dual non-hormonal contraception as noted above; or
• Practices total abstinence from sexual intercourse as her preferred lifestyle; periodic abstinence is not acceptable.
• 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).

You may not qualify if:

• 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 \> 2.0 cm, or any other clinically significant gynecological disorder determined by the investigator to require further evaluation and/or treatment.
• Has unexplained vaginal bleeding outside of the patient's regular menstrual cycle
• 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
• 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
• 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
• 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
• Gastrointestinal disorder affecting absorption or gastrointestinal motility
• Has any additional contraindication to treatment with low-dose estradiol and norethindrone acetate, including:
• Current, known, suspected, or history of breast cancer
• Current, known, or suspected hormone -dependent neoplasia
• 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

Sponsors & Collaborators

• University of Chicago: lead
• Myovant Sciences GmbH: collaborator

Study Sites (6)

University of Chicago South Loop

Chicago, Illinois, 60607, United States

Location

University of Chicago River East

Chicago, Illinois, 60611, United States

Location

University of Chicago DCAM

Chicago, Illinois, 60637, United States

Location

University of Chicago Flossmoor

Flossmoor, Illinois, 60422, United States

Location

University of Chicago Orland Park

Orland Park, Illinois, 60462, United States

Location

University of Chicago Schererville

Schererville, Indiana, 46375, United States

Location

Related Publications (1)

• Alkhrait S, Al-Hendy A, Alkelani H, Karrison T, Laveaux OSM. Surgical myomectomy followed by oral Myfembree vs standard of care (SOUL trial): Study protocol for a randomized control trial. PLoS One. 2024 Jul 2;19(7):e0306053. doi: 10.1371/journal.pone.0306053. eCollection 2024.

  PMID: 38954680 DERIVED

MeSH Terms

Conditions

Metrorrhagia; Pelvic Pain; Menorrhagia; Leiomyoma

Condition Hierarchy (Ancestors)

Uterine Hemorrhage; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Menstruation Disturbances; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Obianuju Sandra Madueke Laveaux, MD MPH

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2022
• First Posted: September 14, 2022
• Study Start: November 20, 2022
• Primary Completion: October 24, 2024
• Study Completion: October 24, 2024
• Last Updated: September 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)