A Phase 3 Multi-Center, 1-Year, Open-Label Study of Setmelanotide in Pediatric Patients Aged 2 to <6 Years of Age With Rare Genetic Causes of Obesity
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 6
- 主要终点
- Percentage of Participants With Greater Than or Equal to (≥) 0.2 Reduction of BMI Z-Score From Baseline to Week 52
研究概览
简要总结
This is a phase 3 open-label, clinical study to evaluate the efficacy, safety and tolerability of setmelanotide over 1 year of treatment, in pediatric participants aged 2 to <6 years with obesity due to either biallelic variants of the pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) genes or Bardet-Biedl Syndrome (BBS).
详细描述
Pediatric participants aged 2 to <6 years with obesity due to either biallelic variants of the POMC, PCSK1 or LEPR genes or BBS will be enrolled into this phase 3 open-label clinical trial at one of approximately 8 clinical centers in North America, Europe, or Australia. All participants will be assigned to receive setmelanotide via daily subcutaneous (SC) injection for 1 year.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have obesity due to either:
- •POMC, PCSK1, or LEPR deficiency, confirmed by genetic testing demonstrating biallelic variants that are interpreted as pathogenic, likely pathogenic, or of undetermined significance (VUS) by the American College of Medical Genetics and Genomics criteria (ACMG), or
- •BBS confirmed clinical and genetic diagnosis
- •Age between 2 to <6 years at the time of informed consent
- •Obesity, defined as body mass index (BMI) ≥97th percentile for age and gender and body weight of at least 15 kilograms (kg) at the time of enrollment.
- •Symptoms or behaviors of hyperphagia
- •Parent or guardian of study participant is able to understand and comply with the requirements of the study (including QD injection regimen and all other study procedures) and is able to understand and sign the written consent/assent.
- •Key Exclusion Criteria
- •Glycated hemoglobin (HbA1c) >9.0% at screening
- •History of significant liver disease
- •Glomerular filtration rate (GFR) <60 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2)
- •History or close family history of melanoma, or participant history of oculocutaneous albinism.
- •Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion)
- •Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
- •Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
- •Significant hypersensitivity to any excipient in the study drug.
- •Inadequate hepatic function
- •Any other uncontrolled endocrine, metabolic or medical condition(s) known to impact body weight
- •Other protocol defined Inclusion/Exclusion criteria may apply.
排除标准
- 未提供
研究组 & 干预措施
Setmelanotide: PPL Group
Participants with POMC)/PCSK1/LEPR biallelic mutations collectively referred to as PPL received setmelanotide at a dose of 0.5 milligrams (mg) per day (QD) via SC injection for 52 weeks. The dose was escalated by increments of 0.5 mg every 2 weeks, if tolerated, at the dose escalation visits (Weeks 2, 4, and 6) to a maximum dose of 0.5 to 2.0 mg QD with the maximum dose based on body weight. Following the last dose in this study, participants who were considered likely to benefit from continued setmelanotide treatment and who had completed this trial could be eligible to enter an open-label long-term extension (LTE) trial with setmelanotide.
干预措施: Setmelanotide (Drug)
Setmelanotide: BBS Group
Participants with BBS received setmelanotide at a dose of 0.5 mg QD via SC injection for 52 weeks. The dose was escalated by increments of 0.5 mg every 2 weeks, if tolerated, at the dose escalation visits (Weeks 2, 4, and 6) to a maximum dose of 0.5 to 2.0 mg QD with the maximum dose based on body weight. Following the last dose in this study, participants who were considered likely to benefit from continued setmelanotide treatment and who had completed this trial could be eligible to enter an open-label long-term extension (LTE) trial with setmelanotide.
干预措施: Setmelanotide (Drug)
结局指标
主要结局
Percentage of Participants With Greater Than or Equal to (≥) 0.2 Reduction of BMI Z-Score From Baseline to Week 52
时间窗: Baseline up to Week 52
A "responder" was defined as a decrease from baseline to 52 weeks in the participant's BMI z-score of ≥0.2. BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2. The BMI Z-scores were based on the World Health Organization's Child Growth Standards 2007 and indicated the number of standard deviations away from the mean. A Z-score of 0 was equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease of BMI Z-score (\< 0) indicated a reduction in BMI from Baseline whereas an increase of BMI-Z score (\> 0) indicated an increase in BMI from Baseline. Baseline was defined as the most recent measurement prior to the first administration of study drug.
Mean Percent Change From Baseline in BMI
时间窗: Baseline, Week 52
Mean percent change from baseline to Week 52 in BMI was reported. BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2. Baseline was defined as the most recent measurement prior to the first administration of study drug.
次要结局
- Mean Absolute Change From Baseline in BMI Z-score(Baseline, Week 52)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From first dose of study drug up to Week 56)
- Mean Change From Baseline in Percent of the 95th Percentile of BMI(Baseline, Week 52)
- Change From Baseline in Body Weight(Baseline, Week 52)
- Number of Participants With TEAEs Graded by Severity(From first dose of study drug up to Week 56)
- Mean Change From Baseline in Bone Age(Baseline, Week 52)
- Number of Participants With Shift From Baseline in Ages & Stages Questionnaires, Third Edition (ASQ-3)(From Baseline to Week 52)