Evaluate the Efficacy and Safety of HMI-115 in Women With Moderate to Severe Endometriosis-associated Pain

A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase 3 Study to Evaluate the Efficacy and Safety of HMI-115 in Women With Moderate to Severe Endometriosis-Associated Pain Over a 24-Week Treatment Period and a 28-Week Extension

A phase 3 study to evaluate the efficacy and safety of HMI-115 in women with moderate to severe endometriosis-associated pain over a 24-week treatment period and a 28-week extension

Inclusion Criteria:

• 1. Premenopausal female subjects, between 18 and 49 years of age, inclusive.
• 2. Has a surgical diagnosis of endometriosis (laparoscopy or laparotomy) as documented by medical records within 10 years before screening.
• 3. Has a Composite Pelvic Signs and Symptoms Score total score of ≥ 6 at screening with a score of at least 2 for DYS and at least 2 for NMPP.
• 4. Subject has reported "moderate" or "severe" for her endometriosis-associated DYS AND NMPP before randomization.
• 5. Subject has at least two consecutive regular menstrual cycle (i.e. 21 to 35 days in duration) prior to randomization.
• 6. Subject agrees to use required (nonhormonal) birth control methods during the entire length of participation in the study and agrees to avoid pregnancy from signing the informed consent until 12 weeks after the last dose.
• 7. Subject agrees to use only those rescue analgesic medications permitted by the protocol during the Screening, Treatment and Posttreatment follow-up Periods for her endometriosis-associated pain.
• 8. Criteria for Extension Treatment Period：Subject who completes treatment of the placebo-controlled double-blind treatment period and assessments at Week 24.

Exclusion Criteria:

• 1. Subject who is pregnant or breastfeeding or is planning a pregnancy during the study period or is less than 6 months post-partum or 3 months post-abortion at the time of entry into the Screening Period or pregnancy before randomization.

• 2. Subject has an intra-uterine device (IUD). Subject is eligible if she removes the IUD 1 month before screening.

• 3. Subject has chronic pelvic pain that is not caused by endometriosis (e.g., interstitial cystitis, irritable bowel syndrome) or has any other chronic pain syndrome (e.g., fibromyalgia, chronic back pain, myofascial pain syndrome, chronic headaches) that requires chronic analgesic or other chronic therapy, which would interfere with the assessment of endometriosis-associated pain.

• 4. Subject with a current history of undiagnosed abnormal genital bleeding.

• 5. Subject with history of hysterectomy and/or bilateral oophorectomy.

• 6. Subject has had surgery for endometriosis within 6 weeks prior to entry into the Screening Period.

• 7. Subject has previous history of a severe, life-threatening or other significant sensitivity to any opioids or non-steroidal anti-inflammatory drugs (NSAIDS) or any contraindication to their use such as gastrointestinal ulcer or bleeding.

• 8. Subject with known hypersensitivity to any of the IMP ingredients.

• 9. Subject has an estimated glomerular filtration rate (eGFR) of < 60mL/min/1.73 m2 at Screening Period.

• 10. Subject is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 30 days prior to the start of Screening Period or 5 half-lives, whichever is longer.

• 11. Subject who has been exposed to HMI-115 treatment.

• 12. Subject has used medications such as hormones, analgesics, medications associated with bone loss, products that affect PRL levels, etc. within specific time window before Screening.

• 13. Subject has clinically significantly abnormal laboratory tests at Screening Period, including:

  1. Alanine transaminase (ALT/SGPT), or aspartate aminotransferase (AST/SGOT) ≥200% of the upper limit of normal, or total bilirubin (unless known diagnosis of Gilbert's syndrome) ≥ 150% of the upper limit of normal range.
  2. Hemoglobin < 100 g/L, Neutrophil count < 1.5×109/ L, Platelet count < 100×109/ L.

• 14. Subject has clinically significantly abnormal laboratory tests at Screening Period, including: Neutrophil count < 1.5×109/ L, Platelet count < 100×109/ L.

• 15. Subject has clinically significant abnormal ECG, or ECG with QTcF > 450 msec at Screening Period.

• 16. Subject has a history or current has malignancy except for treated basal cell carcinoma and cutaneous squamous cell carcinoma of the skin.

• 17. Subject is using any systemic corticosteroids for over 14 days within 3 months prior to Screening or is likely to require treatment with systemic corticosteroids during the study.

• 18. Subject has any of the following conditions within the last 6 months before Screening:

  1. Myocardial infarction, stroke, unstable angina or transient ischemic attack.
  2. Classified as being in New York Heart Association Class III or IV.

• 19. Subjects with body weight greater than 300 pounds or 136 kilograms.

• 20. Any other conditions in the Investigator's opinion that prevent the subject from participating.

• 21. Criteria for Extension Treatment Period： Subjects entering the follow-up period after treatment: subjects with a BMD decrease of ≥ 8.0% or Z-value ≤ -2.0 in any part of the lumbar spine, femoral neck, or total hip compared to baseline.