Mirena for Endometrial Hyperplasia

(SUNFLOWER Trial)

Recruiting at 57 trial locations

Overseen By Bayer Clinical Trials Contact

Age: Any Age

Sex: Female

Trial Phase: Phase 3

Sponsor: Bayer

Must be taking: Progestins

Must not be taking: Injectable hormones

Disqualifiers: Uterine anomaly, Pregnancy, Cancer history, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 5

Duration: 6 months

300 Participants Needed

Trial Summary

What is the purpose of this trial?

Researchers are looking for a better way to treat women with nonatypical endometrial hyperplasia (NAEH). Endometrial hyperplasia is a condition where the lining of the uterus (called the endometrium) becomes too thick. Nonatypical means that the condition is not cancerous. It is often caused by hormone imbalances in women. Symptoms can include abnormal vaginal bleeding or irregular periods. If this condition is not treated, then it may lead to cancer. Currently, oral progestins (OP) which are progesterone (female hormone) capsules taken by mouth, are used to treat NAEH. However, there is still a need for other treatments due to unmet needs. The study treatment, Mirena (also known as BAY 865028), is already available as a type of birth control device. It is inserted into the uterus where it gradually releases progesterone. In this study, researchers want to find out if Mirena works for women with NAEH. They believe it can help by keeping hormone levels balanced in the body. The main purpose of this study is to learn how well Mirena works compared to oral in NAEH in women who have started their periods. For this, the researchers will compare the number of participants with benign endometrium after 6 months of treatment with Mirena or oral progestins. The study participants will be randomly divided equally into one of two treatment groups. Based on their group, participants will receive Mirena, which is inserted into the uterus at the start of the study, or they will take progestins once daily by mouth for 6 months. Each participant will be in the study for around 10 months with up to 5 visits to the study clinic/site. Participants will visit the study clinic: * once before the treatment starts * 3 times with a gap of 3 months between the visits during the treatment * then 1 more time after the treatment ends During the study, the doctors and their study team will: * check participant's health by performing tests such as blood and urine tests * perform vaginal ultrasound and hysteroscopy. Hysteroscopy is a minor surgical procedure where a thin camera will be inserted into the womb to check for any abnormality. Sampling of the endometrial lining (cells in the womb) will be done with a thin tube at the same time. * take samples of womb (endometrial) lining * ask the participants questions about how they are feeling and what adverse events they are having An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatment.

Will I have to stop taking my current medications?

The trial requires that you stop using any long-acting injectable sex-hormone preparations 6 months before starting the study and any short-acting hormonal medications 6 weeks before starting. Other medications are not specifically mentioned, so it's best to discuss with the study team.

What data supports the effectiveness of the treatment Mirena for Endometrial Hyperplasia?

Research shows that the Mirena device, which releases a hormone called levonorgestrel, is effective in treating endometrial hyperplasia (a condition where the lining of the uterus becomes too thick) and is comparable to oral medroxyprogesterone acetate (a hormone therapy). Studies indicate that both treatments help manage the condition and reduce the risk of it returning. ^{1 2 3 4 5}

Is Mirena safe for treating endometrial hyperplasia?

Mirena, a levonorgestrel-impregnated intrauterine device, has been studied for safety in treating endometrial hyperplasia and is generally considered safe. Medroxyprogesterone acetate, another treatment option, has been widely used and is also considered safe, though rare serious allergic reactions can occur. ^{1 2 6 7 8}

How does the Mirena treatment differ from other treatments for endometrial hyperplasia?

The Mirena treatment uses a levonorgestrel-releasing intrauterine device (IUD), which directly delivers the hormone to the uterus, potentially reducing side effects compared to oral treatments like medroxyprogesterone acetate (MPA). This localized delivery can be more effective in managing endometrial hyperplasia and preserving fertility. ^{1 2 3 9 10}

Eligibility Criteria

This trial is for women who have started their periods and are diagnosed with nonatypical endometrial hyperplasia, a condition where the uterus lining becomes too thick but isn't cancerous. Participants should not be currently receiving treatment for this condition.

Inclusion Criteria

I am a woman diagnosed with NAEH regardless of my age or if I have had children.

I am a woman over 16 years old and have started my periods.

Exclusion Criteria

Any diseases or conditions that might interfere with the conduct of the study or the interpretation of the results

Congenital or acquired uterine or cervical anomaly including fibroids, or cervical stenosis that in the opinion of the investigator, would interfere with insertion and/or retention of the intrauterine system (i.e., if they distort the uterine cavity)

I haven't used long-acting sex-hormone injections in the last 6 months or short-acting ones in the last 6 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either Mirena inserted into the uterus or oral progestin daily for 6 months

6 months

3 visits (in-person) with a gap of 3 months between visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

1 visit (in-person)

Treatment Details

Interventions

• Medroxyprogesterone acetate
• Mirena

Trial Overview The study compares Mirena (BAY865028), an intrauterine device releasing progesterone, to oral progestins taken daily. The goal is to see if Mirena is more effective in treating the thickening of the uterus lining over a period of 6 months.

Participant Groups

Group I: Levonorgestrel (BAY865028, Mirena) Experimental Treatment 1 Intervention

Mirena will be inserted into the participant's uterus by the investigator on Day 1. At visit 4 (after 6 months) or if a participant discontinues her study participation prematurely, the Mirena will be removed by the investigator.

Group II: Oral progestin Active Control 1 Intervention

Participants will receive 10mg oral progestin once daily, preferably always at the same time of the day, until visit 4 (after 6 months).

Who Is Running the Clinical Trial?

Bayer

Lead Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

References

1. England pubmed.ncbi.nlm.nih.gov

Relapse risk of endometrial hyperplasia after treatment with the levonorgestrel-impregnated intrauterine system or oral progestogens. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Levonorgestrel-impregnated intrauterine device as treatment for endometrial hyperplasia: a national multicentre randomised trial. [2021]

3. Singapore pubmed.ncbi.nlm.nih.gov

A comparison of the effect of levonorgestrel IUD with oral medroxyprogesterone acetate on abnormal uterine bleeding with simple endometrial hyperplasia and fertility preservation. [2020]

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

Treatment results of endometrial hyperplasia after prospective D-score classification: a follow-up study comparing effect of LNG-IUD and oral progestins versus observation only. [2022]

5. Singapore pubmed.ncbi.nlm.nih.gov

Comparing letrozole with medroxyprogesterone acetate (MPA) as hormonal therapy for simple endometrial hyperplasia without atypia in adult and middle-aged women. [2020]

6. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of the mutagenicity of medroxyprogesterone acetate in vitro and in vivo. [2014]

7. Germany pubmed.ncbi.nlm.nih.gov

Cyclic versus continuous medroxyprogesterone acetate for treatment of endometrial hyperplasia without atypia: a 2-year observational study. [2018]

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

Anaphylaxis from medroxyprogesterone acetate. [2013]

9. Greece pubmed.ncbi.nlm.nih.gov

Endometrial hyperplasia: a prospective randomized study of histopathology, tissue steroid receptors and plasma steroids after abrasio, with or without high dose gestagen treatment. [2013]

10. Singapore pubmed.ncbi.nlm.nih.gov

The efficacy of intrauterine versus oral progestin for the treatment of endometrial hyperplasia. A prospective randomized comparative study. [2020]