FATIMA Trial: EGCG and Vitamin D3 for Prevention of Fibroid Recurrence

Inclusion criteria:

Inclusion Criteria (all inclusion criteria must have been met before randomization unless otherwise specified and exceptions to inclusion criteria may be made at the discretion of the Principal Investigator, provided they are justified and ensure no compromise to the study's scientific integrity or participant safety):

Inclusion Criteria:

1. Has voluntarily signed and dated the informed consent form before initiation of any screening or study-specific procedures.
2. Premenopausal females 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. Moderate to heavy menses defined as PBAC score ≥ 120
   2. Pelvic pain during menses measured on NRS ≥ 4 at baseline
   3. Moderately severe fibroid-related symptoms (a score ³ 25 on the 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 not be pregnant for at least 12 months. Participants may use any form of non-hormonal contraception consistently during the screening period and the randomized treatment period. These may include Diaphragm, cervical cap, spermicides, male and female condoms, copper IUD and sponge. Each one will be explained in detail for the participants. However, the patient is not required to use contraception if she:

   1. Has a sexual partner(s) who was vasectomized at least 6 months before 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).

Exclusion Criteria:

1. Participants with documented vitamin D deficiency (based on previous serum vitamin D level within prior 12 months).
2. 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.
3. Has unexplained vaginal bleeding outside of the patient's regular menstrual cycle.
4. 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.
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 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).
10. 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 papillomavirus testing is negative or if DNA testing for human papillomavirus 16 and 18 DNA testing is negative
11. Has any history of clinical laboratory abnormalities indicating hepatic or gallbladder impairment.
12. Has been a participant in an investigational drug or device study within the 1 month prior to the screening visit.
13. 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.
14. 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 the 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.
15. 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).
16. Has participated in a previous clinical study that included the use of Green tea or Vitamin D3 or has received this treatment within 3 months of the study.
17. Is inappropriate for participation in this study for other reasons, as determined by the investigator, sub-investigator, or medical monitor.