2022-501799-24-00进行中（未招募）3 期
A 12-Month Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase 3 Study to Evaluate the Safety and Efficacy of Daily Subcutaneous Metreleptin Treatment in Subjects with Partial Lipodystrophy
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 16
- 试验地点
- 6
- 主要终点
- Change from Baseline to Month 6 in glycated hemoglobin (HbA1c) in subjects with FPLD in Groups A and C (HbA1c ≥7%)
研究概览
简要总结
To evaluate the efficacy of daily SC metreleptin treatment in subjects with familial partial lipodystrophy (FPLD)
研究设计
- 分配方式
- Randomized
- 主要目的
- Overall Study
- 盲法
- Double (Investigator, Subject, Monitor, Analyst, Carer)
入排标准
- 年龄范围
- 0 years 至 65+ years（0-17 Years, 18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Age ≥12 years at Visit 1
- •Female subjects must be postmenopausal (defined as cessation of menses for at least 1 year), surgically sterile (hysterectomy, bilateral oophorectomy, or tubal ligation), or willing to use a highly effective method of contraception (such methods include combined [estrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation: oral/intravaginal; transdermal/progestogen-only hormonal contraception associated with inhibition of ovulation: oral/injectable; implantable/intrauterine device [IUD]/intrauterine hormone-releasing system [IUS]/bilateral tubal occlusion/vasectomized partner/ sexual abstinence) for the duration of the study (from the time they sign an informed consent/assent form [ICF], until 4 weeks after the last dose of study treatment). Hormonal contraception alone (including oral, injectable, transdermal, and implantable) is not acceptable; an additional barrier method must be used. Intravaginal hormonal contraception or IUS alone are allowed per Investigator’s discretion. Subjects will not be permitted to commence oral contraceptives while taking study treatment during the study.
- •Male subjects must be surgically sterile or willing to use an acceptable method of contraception for the duration of the study (from the time they sign an ICF), until 4 weeks after the last dose of study treatment. An acceptable method of contraception would be a barrier method, such as condoms, restraining from having sex, or a partner using the approved methods of contraception for female subjects as per Inclusion Criteria #
- •Subjects who are blood/egg/sperm donors should be willing to halt donations during the study and for 4 weeks following their last dose of study treatment.
- •Subjects who are willing to provide informed consent/assent prior to any study-specific procedures. If a minor, the subject has a parent or legal guardian able to read, understand, and sign the ICF and/or a Child Assent Form (if applicable), communicate with the Investigator, and understand and comply with the protocol requirements. Adolescent subjects must also read and understand the Child Assent Form
- •Subjects who are willing to follow the dietary restrictions recommended by the Investigator.
- •Diagnosis of FPLD, defined as: • Clinical diagnosis of FPLD based on deficiency of subcutaneous body fat in a partial fashion assessed by physical examination and low skinfold thickness in anterior thigh by caliper measurement (males ≤10 mm and females ≤22 mm), plus 1 of the following: o Documented genetic diagnosis of FPLD (mutations in genes known to be associated with lipodystrophy, e.g., LMNA, PPARG, AKT2, or PLIN1). OR o Documented evidence of positive family history (first-degree biological relative) of FPLD (based on genetic or clinical diagnosis) PLUS 1 minor criterion (below). OR o 2 minor criteria (below) in the absence of a genetic diagnosis or family history, plus all the additional criteria (below, following the minor criteria). MINOR Criteria: Diabetes mellitus with requirement for high doses of insulin, e.g., requiring ≥200 U/day, ≥2 U/kg/day, or currently taking U-500 insulin. Presence of acanthosis nigricans on physical examination. History of polycystic ovary syndrome (PCOS) or PCOS-like symptoms (hirsutism, oligomenorrhea, and/or polycystic ovaries). History of pancreatitis associated with hypertriglyceridemia. Evidence of non-alcoholic fatty liver disease (NAFLD): hepatomegaly and/or elevated transaminases in the absence of a known cause of liver disease or radiographic evidence of hepatic steatosis (e.g., on former ultrasound, magnetic resonance imaging [MRI] or computed tomography [CT]). Additional Criteria (required in the absence of a genetic diagnosis or documented evidence of family history): Age ≥18 years at Visit 1 Leptin levels <8.0 ng/mL in males and <12.0 ng/mL in females. BMI <35 kg/m
- • Subcutaneous body fat distribution pattern indicative of FPLD assessed by DXA at Screening, including percent fat mass of the trunk to percent fat mass of the legs (Fat Mass Ratio FMR) >1.
- •Confirmation by the Investigator that the potential differential diagnosis of FPLD has been excluded (e.g., Cushing’s syndrome, anorexia nervosa, cachexia, diencephalic syndrome, Rabson-Mendenhall syndrome, leprechaunism, SHORT syndrome, mandibuloacral dysplasia, progeroid syndromes)
- •Subjects with poor metabolic control defined as: • HbA1c ≥7% (at Visit 1 and Visit 3) and/or • Fasting TGs ≥500 mg/dL (5.65 mmol/L, at Visit 1 and Visit 3)
- •Subjects with HbA1c ≥7% should be receiving optimized stable antidiabetic therapy for at least 3 months prior to Screening and their diet (as reported by the subjects) should be stable and in line with medical recommendations.
- •Subjects with diabetes and HbA1c <7% should be receiving stable treatment regimen (diet and/or antidiabetic treatment) for at least 6 weeks prior to Screening and their diet (as reported by the subjects) should be stable and in line with medical recommendations.
- •Subjects with fasting TGs ≥500 mg/dL (5.65 mmol/L) should be receiving a stable lipid-lowering therapy for at least 6 weeks prior to Screening (unless these medications were not tolerated or are contra-indicated) and their diet (as reported by the subjects) should be stable and in line with medical recommendations.
- •Subjects receiving antidiabetic and/or lipid-lowering therapy prior to the beginning of the study must be kept stable on optimized and stable dose for at least 6 weeks prior to Randomization (Visit 4). For subjects on insulin, a stable dose is defined as no more than 20% fluctuation. For all other therapies, a stable dose is defined as no dose change.
- •Negative pregnancy test (urine or serum) for female subjects of childbearing potential.
排除标准
- •Previous treatment with metreleptin.
- •Known history of drug or alcohol abuse within 1 year prior to Screening as assessed according to the Investigator’s judgment
- •Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 calculated by CKD-EPI for subjects ≥18 years of age and by Bedside Schwartz for subjects <18 years of age.
- •For females only: currently pregnant (confirmed with a positive pregnancy test) or breastfeeding
- •Any condition where, in the opinion of the Investigator, participation in this study may pose a significant risk to the subject or could render the subject unable to successfully complete the study (e.g., life expectancy <12 months).
- •Subjects whose antidiabetic/lipid-lowering therapies and/or other concomitant medications that may affect the primary endpoint results (such as appetite suppressing medications) are not stable at Screening and are likely to require a change in dose during the treatment period
- •Subjects with ongoing or recent (within the last 3 months prior to Screening) episode of acute pancreatitis
- •Diagnosis of clinically significant hematological abnormalities (including but not limited to clinically significant leukopenia, neutropenia, bone marrow abnormalities, leukemia or lymphoma, or clinically significant pathological lymphadenopathy).
- •Malignancy that is ongoing/not in remission or that currently requires or has required active treatment within the past 3 years (with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ [e.g., breast carcinoma, cervical cancer in situ] that have undergone potentially curative therapy).
- •Leptin levels >20.0 ng/mL
- •Acquired partial lipodystrophy (APL)
- •Radiation induced PL
- •Subjects diagnosed with Cushing’s syndrome
- •Treatment with any Investigational Medicinal Product (IMP) within 6 months or 5 times the terminal half-life of the corresponding IMP, whichever is longer, before the Screening visit
- •Subjects with prior severe hypersensitivity reactions to any of the metreleptin product components
- •Known to have tested positive for human immunodeficiency virus (HIV) or known to be diagnosed with HIV-related LD. Positive HIV test in countries requiring HIV testing.
- •Are immunocompromised or receiving immunomodulatory drugs
结局指标
主要结局
Change from Baseline to Month 6 in glycated hemoglobin (HbA1c) in subjects with FPLD in Groups A and C (HbA1c ≥7%)
Change from Baseline to Month 6 in glycated hemoglobin (HbA1c) in subjects with FPLD in Groups A and C (HbA1c ≥7%)
Percent change from Baseline to Month 6 in fasting triglycerides (TGs) in subjects with FPLD in Groups B and C (TG ≥500 mg/dL [5.65 mmol/L])
Percent change from Baseline to Month 6 in fasting triglycerides (TGs) in subjects with FPLD in Groups B and C (TG ≥500 mg/dL [5.65 mmol/L])
次要结局
- Change from Baseline to Month 6 in FBG in Groups A and C (HbA1c ≥7%)
- Change from Baseline to Month 6 in FBG in subjects with FBG above upper limit of normal (ULN)
研究者
Tracy Cunningham
Scientific
Amryt Pharmaceuticals Designated Activity Company
研究点 (6)
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