A Study to Assess the Efficacy and Safety of HMI-115(HMI-115 is the Company Giving Name of This Specific Prolactin Receptor Antibody) in Subjects With Endometriosis

• Status: Not yet recruiting
• Trial end date: 2023-09-01
• Target enrollment: 0
• Participant gender: Female

Summary

This study is designed to evaluate the safety and efficacy of HMI-115 compared to placebo over a 12 weeks period on subjects with moderate to severe endometriosis-associated pain.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hope Medicine (Nanjing) Co., Ltd

Criteria

Inclusion Criteria:

1. Pre-menopausal female subjects, between 18 and 49 years of age, inclusive, at the time of signing informed consent.

2. Subject must have a clinical diagnosis of endometriosis (laparoscopy or laparotomy) as documented by medical records within 10 years before screening.

3. Subject must have 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 must have reported at Baseline at least 2 days of "moderate" or "severe" pain for DYS and NMPP NRS score of at least 4.

5. Mammography or contrast-enhanced breast MRI performed within the last 12 months prior to randomization without clinically significant abnormal findings in subjects aged 40 and over only (subject with Breast Imaging-Reporting and Data System (BI-RADS) Classification 1 - 3 is eligible for randomization).

6. Subject must have at least two consecutive regular menstrual cycle (i.e. 21 to 35 days in duration) prior to Day 1.

7. 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 3 months after the last dose.

8. Subject must agree to use only those rescue analgesics (i.e. not prophylaxis) permitted by the protocol during the Screening, Treatment and Post treatment follow up Periods for her endometriosis-associated pain.

9. In the Investigator's opinion, subject is able to understand the nature of the study and any risk involved in participation in this study and is willing to cooperate and comply with the protocol restrictions and requirements, including transvaginal ultrasound (TVU).

10. Subject agrees not to participate in another interventional study while participating in the present study.

11. Subject who is willing to limit alcohol consumption during the study to no more than approximately one alcoholic drink or equivalent (1 glass is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day).

Exclusion Criteria:

1. Subject has a positive Real-time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) at the Screening Visit or prior to randomization.

2. Subject has clinical signs and symptoms consistent with SARS-CoV-2 infection; e.g., fever, dry cough, dyspnea, sore throat, fatigue, loss of smell or taste, confirmed with positive SARS-CoV-2 test result within 4 weeks prior to Screening or any time prior to randomization.

3. Subject who had severe course of Corona Virus Disease 2019 (COVID-19) (extracorporeal membrane oxygenation (ECMO), mechanically ventilated).

4. Recent (within 14 days prior to screening or randomization) exposure to someone who has COVID-19 symptoms or positive test result.

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

6. Subject has an intra-uterine device (IUD).

7. Subject has chronic pelvic pain that is not caused by endometriosis 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, or that would interfere with the assessment of endometriosis-related pain.

8. Subject has clinically significant gynecologic condition other than endometriosis, including but not limited to:

1. Ovarian cyst>5 cm (except confirmed endometrioma) that persists on repeat TVU;

2. Single fibroid ≥ 4 cm or multiple (> 4) fibroids that measure ≥2 cm or symptomatic submucosal fibroid of any size on screening TVU;

3. Any ovarian tumors or pelvic masses of unclear etiology requiring further diagnostic procedures;

4. Acute or chronic endometritis

9. Subject has a current history of undiagnosed abnormal genital bleeding.

10. Subject has history of hysterectomy and/or bilateral oophorectomy.

11. Subject has had surgery for endometriosis within the 4 weeks prior to entry into the Screening Period.

12. Subject plans to schedule elective surgery during the study execution.

13. Subject has known any history of anterior pituitary, posterior pituitary or hypothalamic dysfunction, including but not limited to prolactinomas, hypogonadism, growth hormone deficiency.

14. Subject has a current history of thyroid dysfunction (hyper-, or hypothyroidism).

15. Subjects with past or present pituitary tumor growth as confirmed by a sellar magnetic resonance imaging (MRI) with contrast at screening period or has contraindications to contrast used in MRI.

16. Subjects with immunocompromised status.

17. Subjects with a personal or family history of Multiple Endocrine Neoplasia syndrome type 1 (MEN1).

18. 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.

19. Subject with known hypersensitivity to any of the Investigational Medicinal Product (IMP) ingredients.

20. Subject is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) (e.g., positive urine drug screening result) of drug or alcohol abuse or dependence.

21. Subject has, in the Investigator's opinion, uncontrolled hypertension (systolic blood pressure (SBP) > 159 mmHg, diastolic blood pressure (DBP) > 99 mmHg).

22. Subject has an estimated glomerular filtration rate (eGFR) of < 60ml/min/1.73 m2 (using the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) formula) at Screening period.

23. Subject is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 90 days prior to start of Screening Period or 5 half lives, whichever is longer. If a subject has participated in an investigational study with hormonal treatment.

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

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

1. Alanine transaminase (ALT/SGPT), 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 < 10 g/dL, Neutrophil count < 1500 mm3, Platelet count < 100 × 103/mm3.

26. Subject has a cervical cytology collected during the Screening Period shows evidence of malignancy or pre-malignant changes.

27. Subject has clinically significant abnormal ECG, or ECG with Abbreviation: QT interval corrected for heart rate using Fridericia's correction formula(QTcF) > 450 msec at Screening Period.

28. Subject has a positive Screening test result for hepatitis A virus immunoglobulin M (HAV - IgM), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), detected hepatitis C virus(HCV) RNA (for positive anti-HCV only), or positive human immunodeficiency virus (HIV) or HIV antibody (HIV Ab). The HIV/HIV Ab results will be kept confidential by the study sites.

29. Subject has a history of active malignancy (with or without systemic chemotherapy), except treated basal cell carcinoma of the skin.

30. 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 course of the study. Over-the-counter and prescription topical, inhaled or intranasal corticosteroids are allowed.

31. Subject has a medical history of psychiatric disorder at any time (e.g., depression, schizophrenia, bipolar disorder) or has a history of epilepsy.

32. Subject has any of the following conditions within 6 months prior to Screening:

1. Myocardial infarction, stroke, unstable angina or transient ischemic attack.

2. Classified as being in New York Heart Association Class III or IV.

33. Subject has a history of osteoporosis or other metabolic bone disease, or including any one or more of the following:

1. Low bone mass (Z-score ≤ -2.0 on screening dual energy X-ray(DEXA) scan [lumbar spine, femoral neck or total hip Bone mineral density(BMD)]) OR

2. Body weight greater than 300 pounds or 136 kilograms (due to limits of DEXA scanners) or any condition that would interfere with obtaining adequate DEXA measurements (e.g., history of spinal surgery, severe scoliosis, hardware or artifact overlying the region of interest, including umbilical ring with refusal to remove)

3. History of fragility fracture OR

4. History or presence of an unstable condition that is associated with a decrease in BMD (e.g., uncontrolled hyperparathyroidism, anorexia nervosa)

34. Any other conditions in the investigator's opinion that prevent the subject from participating.

35. Subject works in the investigational site or has an immediate family member (e.g. spouse, parent/legal guardian, sibling or child) who works in the investigational site or is a staff of the Sponsor directly involved with this study.