Myfembree for Fibroids

(SOUL Trial)

Recruiting at 5 trial locations

Overseen By Samar Alkhrait, MD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Chicago

Must be taking: Myfembree

Must not be taking: Bisphosphonates, Glucocorticoids, others

Disqualifiers: Osteoporosis, Liver disease, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

136 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that certain medications for bone density loss and high doses of systemic glucocorticoids are not allowed. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Myfembree for treating fibroids?

Research shows that Myfembree, a combination of relugolix, estradiol, and norethindrone acetate, significantly reduces heavy menstrual bleeding and improves symptoms related to uterine fibroids. Studies found it to be effective and well-tolerated, with improvements in quality of life for women with fibroids. ^{1 2 3 4 5}

Is Myfembree safe for humans?

Myfembree, a combination of relugolix, estradiol, and norethindrone acetate, has been generally well tolerated in clinical trials for uterine fibroids, with the most common side effects being hot flashes. Long-term use did not lead to significant bone loss in most women. ^{1 2 3 5 6}

How is the drug Myfembree unique for treating uterine fibroids?

Myfembree is unique because it combines relugolix, estradiol, and norethindrone acetate into a once-daily oral pill that effectively reduces heavy menstrual bleeding and other symptoms of uterine fibroids, while minimizing bone loss and hot flashes, which are common side effects of similar treatments. ^{1 2 3 4 7}

What is the purpose of this trial?

This trial is testing Myfembree, a pill that combines three medications, to help women who have had surgery for fibroids. The goal is to delay the return of fibroid symptoms and improve their quality of life. Myfembree works by lowering certain hormone levels and balancing others to reduce heavy menstrual bleeding and other symptoms.

Research Team

Obianuju Sandra Madueke Laveaux, MD MPH

Principal Investigator

University of Chicago

Eligibility Criteria

This trial is for premenopausal women aged 18 or older with uterine fibroids confirmed by ultrasound, experiencing heavy menstrual bleeding or pelvic pain. Participants must not be pregnant, have certain medical conditions like osteoporosis or significant cardiovascular disease, and agree to use non-hormonal contraception if sexually active.

Inclusion Criteria

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

I experience heavy periods, pelvic pain during periods, or severe symptoms from fibroids.

My recent endometrial biopsy showed no significant issues.

Exclusion Criteria

I have had a procedure for fibroids or abnormal bleeding in the last 6 months.

My endometriosis was confirmed by surgery within the last 10 years.

Has a history of clinically significant condition(s) including, but not limited to: Untreated thyroid dysfunction or palpable thyroid abnormality (patients with adequately treated hypothyroidism who are stable on medication are not excluded), 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, 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, 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), Has participated in a previous clinical study that included the use of Relugolix or has received this treatment within 3 months of the study, 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), Is inappropriate for participation in this study for other reasons, as determined by the investigator, sub-investigator, or medical monitor

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Myomectomy

Participants undergo uterine sparing surgery to remove fibroids

1-2 weeks

Treatment

Participants receive daily dosed Myfembree for 24 months to delay fibroid recurrence

24 months

Follow-up

Participants are monitored for fibroid recurrence, pelvic pain, and quality of life

36 months

Treatment Details

Interventions

• Myfembree Oral Product

Trial Overview The SOUL trial is testing whether taking Myfembree orally after surgical myomectomy can delay the return of fibroid symptoms compared to standard care. Myfembree combines relugolix with estradiol and norethindrone acetate and aims to prolong improved quality of life.

Participant Groups

Group I: Study drug Myfembree Experimental Treatment 1 Intervention

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.

Group II: Parallel group for participants who opt not to be randomized Experimental Treatment 1 Intervention

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.

Group III: Standard of Care Active Control 1 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.

Myfembree Oral Product is already approved in United States for the following indications:

Approved in United States as Myfembree for:

• Heavy menstrual bleeding associated with uterine fibroids
• Moderate to severe pain associated with endometriosis

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Myovant Sciences GmbH

Industry Sponsor

Trials

23

Recruited

12,500+

Findings from Research

The combination of relugolix, estradiol, and norethisterone acetate (Ryeqo®; Myfembree®) effectively reduces heavy menstrual bleeding and improves other symptoms associated with uterine fibroids, as demonstrated in two phase 3 LIBERTY trials.

This treatment is generally well tolerated, with minimal risk of clinically significant bone loss over up to 2 years, making it a safe and convenient once-daily option for premenopausal women suffering from symptomatic uterine fibroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix/Estradiol/Norethisterone (Norethindrone) Acetate: A Review in Symptomatic Uterine Fibroids. Syed, YY.[2022]

In a study involving 241 Black or African American women with uterine fibroids, 82.9% achieved significant reductions in heavy menstrual bleeding after 52 weeks of treatment with once-daily relugolix combination therapy, indicating its high efficacy in this population.

The treatment was well-tolerated, with preserved bone mineral density and manageable side effects, such as hot flushes and headaches, suggesting that relugolix combination therapy is a safe option for managing uterine fibroid symptoms in Black or African American women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix combination therapy in Black/African American women with symptomatic uterine fibroids: LIBERTY Long-Term Extension study. Stewart, EA., Al-Hendy, A., Lukes, AS., et al.[2023]

In a study involving 509 premenopausal women, relugolix combination therapy significantly reduced symptom severity and distress from uterine fibroids compared to placebo, with a notable decrease in bleeding and pelvic discomfort after 24 weeks of treatment.

Participants receiving relugolix also reported substantial improvements in health-related quality of life, including emotional well-being and physical and social activities, indicating that the therapy effectively alleviates the burdens associated with uterine fibroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life with relugolix combination therapy for uterine fibroids: LIBERTY randomized trials. Stewart, EA., Lukes, AS., Venturella, R., et al.[2023]

Elagolix combined with estradiol and norethindrone acetate significantly reduces heavy menstrual bleeding (HMB) in premenopausal women with uterine fibroids, achieving a reduction in menstrual blood loss in 68.5% to 76.5% of participants in Phase 3 trials.

While effective, the treatment is associated with common side effects such as hot flushes, nausea, and headaches, highlighting the need for careful consideration of warnings and precautions in patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oriahnn: New Drug Approved for Treating Heavy Menstrual Bleeding in Women With Uterine Fibroids. Lynch, SE., Mayer, DC.[2021]

In a post hoc analysis of the LIBERTY 1 and LIBERTY 2 trials involving 124 European women, relugolix combination therapy (relugolix-CT) significantly reduced uterine fibroid-associated symptoms, with 85.4% of women responding positively compared to only 19.1% in the placebo group.

Relugolix-CT not only improved menstrual blood loss and pain but also preserved bone mineral density, indicating it is a safe and effective treatment option for women suffering from heavy menstrual bleeding due to uterine fibroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix combination therapy in European women with symptomatic uterine fibroids: a subgroup analysis from the randomized phase 3 LIBERTY pivotal trials. Venturella, R., Rechberger, T., Zatik, J., et al.[2023]

In a study involving 509 premenopausal women with uterine leiomyomas, relugolix combination therapy (relugolix-CT) significantly reduced moderate-to-severe pain, with 45.2% of participants experiencing minimal-to-no pain after 24 weeks compared to only 13.9% in the placebo group.

Relugolix-CT was particularly effective in alleviating menstrual pain, with 65.0% of women reporting minimal-to-no pain during menstrual days, highlighting its potential as a clinically meaningful treatment for pain associated with uterine leiomyomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix Combination Therapy for Uterine Leiomyoma-Associated Pain in the LIBERTY Randomized Trials. Stewart, EA., Lukes, AS., Venturella, R., et al.[2022]

In two phase 3 trials involving 770 women, once-daily relugolix combination therapy significantly reduced heavy menstrual bleeding compared to placebo, with 73% and 71% of participants responding positively in the treatment groups versus only 19% and 15% in the placebo groups.

The therapy also showed improvements in key secondary outcomes like pain and distress from bleeding, while maintaining bone mineral density, indicating a safer profile compared to other treatments that may cause bone loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy. Al-Hendy, A., Lukes, AS., Poindexter, AN., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Relugolix/Estradiol/Norethisterone (Norethindrone) Acetate: A Review in Symptomatic Uterine Fibroids. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Relugolix combination therapy in Black/African American women with symptomatic uterine fibroids: LIBERTY Long-Term Extension study. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Quality of life with relugolix combination therapy for uterine fibroids: LIBERTY randomized trials. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Oriahnn: New Drug Approved for Treating Heavy Menstrual Bleeding in Women With Uterine Fibroids. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Relugolix combination therapy in European women with symptomatic uterine fibroids: a subgroup analysis from the randomized phase 3 LIBERTY pivotal trials. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Relugolix Combination Therapy for Uterine Leiomyoma-Associated Pain in the LIBERTY Randomized Trials. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy. [2022]