Directed Ablation of Uterine Fibroids Using a Noninvasive Approach

Directed Ablation of Uterine Fibroids Using a Noninvasive Approach (DIANA)

The purpose of this clinical study is to assess the safety and effectiveness of the Mirabilis System for treating uterine fibroids in women who are seeking relief from fibroid-related abnormal uterine bleeding but want to avoid hysterectomies or other surgical procedures. The Mirabilis System is an investigational device that delivers high-intensity focused ultrasound (HIFU) to the uterus using integrated ultrasound imaging guidance to offer noninvasive treatment for uterine fibroids. With the Mirabilis System, HIFU is applied noninvasively through the skin using an applicator that is placed against the abdomen. No incisions or surgical procedures are required. During this study, eligible patients will have one or more fibroids treated with the Mirabilis System and will then remain in the study for a total of 36 months after treatment to monitor the occurrence of adverse events. Primary endpoints will be assessed at 12 months after treatment, while secondary endpoints will be assessed at variable times ranging from immediately after treatment up to 36 months after treatment.

Inclusion Criteria:

1. Female patients between the ages of 18 to 50 years of age.
2. Patients must have 1-3 treatable fibroids with at least one distorting the endometrial cavity.
3. Patients must have at least 1 treatable fibroid or cluster of fibroids that measures between 2 cm to 7 cm in diameter with diagnostic ultrasound.
4. Patients must have primary complaint of prolonged and/or heavy menstrual bleeding.
5. Patients must be in generally good health and seeking relief of fibroid related symptoms.
6. Patients must have a normal Pap smear within 36 months of enrollment, including an endometrial biopsy, if clinically indicated.
7. Patients must be willing to adhere to the study schedule.
8. Patients must have a baseline Menstrual Pictogram (MP) score between 150 mL and 500 mL.
9. Patients must agree to abstain from having other treatments or therapies for fibroids, including procedures (i.e. uterine artery embolization, hysterectomy, radiofrequency ablation of fibroids, etc.) or medications (i.e. hormone therapy for treatment of fibroids; prescription or over the counter medications, including standard, homeopathic, or naturopathic medications, for the treatment of fibroids; dietary supplements taken for the treatment of fibroids, etc.). Exceptions include the use of analgesics or other pain control medications.
10. Patients must have regular cyclical menstrual periods.
11. Patients must be willing to maintain use of their current form of birth control during screening and for 12 months after treatment.
12. Patients must be willing and able to consent to participate in the study.

Exclusion Criteria:

1. Patients who are pregnant, suspected to be pregnant, or wish to become pregnant.

2. Patients unable or unwilling to use only the sanitary products provided by Sponsor during their participation in the study.

3. Patients with fibroids that are deeper than the maximal treatment depth of the Mirabilis System.

4. Patients with fibroids that have certain MRI characteristics including:

   1. A hyper-intense appearance on T2-weighted MRI where the fibroid tissue appears brighter than surrounding myometrium
   2. Features consistent with high perfusion, low perfusion, non-perfusion, infarct, or ischemia on gadolinium-enhanced MRI
   3. Features consistent with extensive degeneration
   4. Fibroids are not quantifiable on MRI
   5. Any endometrial polyp 1 cm or larger
   6. Type 0 fibroids (pedunculated intracavitary)

5. Patients with known endometrial hyperplasia.

6. Patients planning or seeking additional therapies for the treatment of fibroids and/or abnormal uterine bleeding.

7. Patients with other pelvic masses of unknown etiology.

8. Patients who are postmenopausal.

9. Patients with an active diagnosis of cancer of any type.

10. Patients on hormone therapy such as Depo-Provera, Lupron, etc.

11. Patients who within 6 months prior to enrollment had procedures or surgery for the fibroid(s) to be treated as part of this clinical study.

12. Patients with known or suspected bleeding disorders.

13. Patients currently taking anticoagulant therapy.

14. Patients with anemia (hematocrit < 30).

15. Patients with known or suspected endometriosis, adenomyosis, endometrial hyperplasia, and/or active pelvic infection.

16. Patients with visible or suspected scars that are likely to be in the potential HIFU beam path.

17. Patients with an IUD or other implants that cannot be removed from the potential HIFU beam path prior to treatment.

18. Patients who have sensory loss or dysesthesia in the area to be treated.

19. Patients with a history of abdominoplasty or liposuction in the potential HIFU beam path.

20. Patients who currently use illicit drug(s) or abuse alcohol (defined as regular consumption of ≥ 4 alcoholic drinks per day).

21. Patients participating in other clinical studies, except observational or registry studies.

22. Patients unable to tolerate gadolinium enhanced MRI procedures.

23. Patients with significant systemic disease.

24. Patients with known or suspected adhesions in the HIFU beam path. This includes patients who have had abdominoplasty, multiple abdominal surgeries, documented abdominal or pelvic adhesions observed during any prior laparotomy or laparoscopy, surgical mesh placement in the lower abdomen, abdominal abscess such as ruptured appendicitis and tubo-ovarian abscess, or multiple liposuction procedures of the lower abdomen.

25. Patients who cannot or are unlikely to adhere to the study schedule.

26. Patients with a significant psychiatric condition.

27. Patients who lack the capacity to self-consent.

28. Patients with chronic steroid use.

29. Patients on immunosuppressive therapy.

30. Inadequate ultrasound image quality during pre-treatment planning or treatment delivery.

31. The uterus size does not allow the Safety Margin to fit entirely within the uterus while the Target Volume is positioned on the fibroid to be treated.

32. Bowel, bladder, bone, or other sensitive tissue cannot be removed from or avoided by the HIFU beam path.

33. Any other reason for which the individual patient is not appropriate or suitable for participation.