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

Официальное название

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

Обзор

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

Вмешательства

• Препарат HMI-115
  HMI-115 is human monoclonal antibody （120mg/vail）
• Препарат Placebo
  Placebo （0mg/vail）

Первичные конечные точки

• Change from Baseline (CFB) in dysmenorrhea (DYS) measured by Numeric Rating Scale (NRS) at Week 12 [Срок оценки: week 12]
• CFB in non-menstrual pelvic pain (NMPP) measured by NRS at Week 12 [Срок оценки: week 12]

Вторичные конечные точки (8)

• CFB in DYS measured by NRS at Week 24 [Срок оценки: week 24]
• CFB in NMPP measured by NRS at Week 12 [Срок оценки: week 24]
• CFB in average overall pelvic pain measured by NRS at Week 12 and week 24 [Срок оценки: Week 12 and week 24]
• CFB in DYSP measured by NRS at Week 12 and week 24 [Срок оценки: Week 12 and week 24]
• Changes in the number of remedial analgesics allowed to be used compared to baseline [Срок оценки: Week 12 and week 24]
• Adverse Events [Срок оценки: During the clinical study period]
• To investigate the pharmacokinetics (PK) characteristic of HMI-115, Serum trough concentrations at each time point and descriptive statistics. [Срок оценки: Before the first intervention、Week 2、Week 4、Week 8、Week 12、Week 16、Week 20、Week 24、Week 32、Week 40、Week 52]
• To investigate the immunogenicity of HMI-115：Anti-drug antibody (ADA) and Neutralizing antibody (NABs) [Срок оценки: Before the first intervention、Week 2、Week 4、Week 8、Week 12、Week 16、Week 20、Week 24、Week 32、Week 40、Week 52]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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:

• 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.
• 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:

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 5 центров

• Peking Union Medical College Hospital — Пекин
• Nanjing Women and children's healthcare hospital — Nanning
• Second Affiliated Hospital of Soochow University — Suzhu
• The International Peace Maternity and Child Health Hospital of the China Welfare Institute — Шанхай
• Tianjin Medical University General Hospital — Тяньцзинь

Идентификаторы

NCT: NCT07318688 · HMI-115ENDO302

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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