A Phase 3, Randomized, Double-Blind Trial of Two Formulations of Setmelanotide (Daily and Weekly) With a Crossover to Open-Label Once Weekly Setmelanotide in Patients With Specific Gene Defects in the Melanocortin-4 Receptor Pathway Who Are Currently on a Stable Dose of the Once Daily Formulation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 7
- 主要终点
- Maximum Drug Concentration (Cmax) of Setmelanotide After QD Administration in the Run-in Period
研究概览
简要总结
A trial to compare the weekly and daily formulations of setmelanotide in participants with genetic defects in the melanocortin-4 receptor pathway.
详细描述
This study is designed to compare the safety, pharmacokinetics, and efficacy of weekly and daily formulations of setmelanotide in participants with obesity associated with biallelic or heterozygous POMC (pro-opiomelanocortin), PCSK1 (proprotein convertase subtilisin/kexin Type 1), LEPR (leptin receptor) genetic variants, and participants with Bardet-Biedl Syndrome (BBS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Biallelic or heterozygous POMC/PCSK1 or LEPR (PPL) genetic variants or Bardet-Biedl syndrome (BBS), for which they are being treated with QD setmelanotide.
- •6 years or older at screening.
- •Taking the setmelanotide QD formulation for at least 6 months in the RM-493-022 (NCT03013543) study with acceptable safety and tolerability, and dose level.
- •Participant and/or parent or guardian is able to communicate well with the Investigator, to understand and comply with the requirements of the study and is able to understand and sign the written informed consent/assent.
- •Use of a highly effective form of contraception throughout the study and for 90 days following the study.
排除标准
- •Glycosylated hemoglobin (HbA1C) >9.0% at screening.
- •Anti-obesity medications within 3 months prior to starting the Run-in Period.
- •History of significant liver disease or liver injury.
- •Glomerular filtration rate <30 milliliter per minute (mL/min).
- •Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions.
- •Major psychiatric disorders.
- •Any suicidal ideation or behavior, or any lifetime history of a suicide attempt.
- •Significant hypersensitivity to any excipient in the study drug.
- •Inability to comply with the QW and QD injection regimens.
- •Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing, with the exception of a setmelanotide clinical trial.
- •Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
DB Period: Setmelanotide 25 mg QW
Participants who received 2.5 mg setmelanotide QD in the run-in period, received SC injection of 25 mg setmelanotide QW and placebo matched to setmelanotide QD for 13 weeks in the DB period.
干预措施: Setmelanotide 25 mg (Drug)
Run-in Period: Setmelanotide 2 mg QD
Participants received subcutaneous (SC) injection of 2 mg setmelanotide once daily (QD) for 1 week in the run-in period.
干预措施: Setmelanotide 2 mg (Drug)
Run-in Period: Setmelanotide 2.5 mg QD
Participants received SC injection of 2.5 mg setmelanotide QD for 1 week in the run-in period.
干预措施: Setmelanotide 2.5 mg (Drug)
Run-in Period: Setmelanotide 3 mg QD
Participants received SC injection of 3 mg setmelanotide QD for 1 week in the run-in period.
干预措施: Setmelanotide 3 mg (Drug)
DB Period: Setmelanotide 20 mg QW
Participants who received 2 mg setmelanotide QD in the run-in period, received SC injection of 20 mg setmelanotide once weekly (QW) and placebo matched to setmelanotide QD for 13 weeks in the DB period.
干预措施: Setmelanotide 20 mg (Drug)
DB Period: Setmelanotide 3 mg QD
Participants who received 3 mg setmelanotide QD in the run-in period, received SC injection of 3 mg setmelanotide QD and placebo matched to setmelanotide QW for 13 weeks in the DB period.
干预措施: Setmelanotide 3 mg (Drug)
DB Period: Setmelanotide 30 mg QW
Participants who received 3 mg setmelanotide QD in the run-in period, received SC injection of 30 mg setmelanotide QW and placebo matched to setmelanotide QD for 13 weeks in the DB period.
干预措施: Setmelanotide 30 mg (Drug)
OL Period: Setmelanotide 20 mg QW
Participants who received 2 mg setmelanotide QD in the run-in period and 20 mg setmelanotide QW in the DB period, received SC injection of 20 mg setmelanotide QW for 13 weeks in the OL period.
干预措施: Setmelanotide 20 mg (Drug)
OL Period: Setmelanotide 25 mg QW
Participants who received 2.5 mg setmelanotide QD in the run-in period and 25 mg setmelanotide QW in the DB period, received SC injection of 25 mg setmelanotide QW for 13 weeks in the OL period.
干预措施: Setmelanotide 25 mg (Drug)
OL Period: Setmelanotide 30 mg QW
Participants who received 3 setmelanotide QD in the run-in period and 3 mg setmelanotide QD or 30 mg setmelanotide QW in the DB period, received SC injection of 30 mg setmelanotide QW for 13 weeks in the OL period.
干预措施: Setmelanotide 30 mg (Drug)
结局指标
主要结局
Maximum Drug Concentration (Cmax) of Setmelanotide After QD Administration in the Run-in Period
时间窗: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose at Week -1
Maximum drug concentration determined directly from individual concentration-time data.
Cmax of Setmelanotide After QW Administration
时间窗: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours postdose at Week 14
Maximum drug concentration determined directly from individual concentration-time data. Data are reported by dose level (treatment regimen) in the OL Period and dosing sequence (QD-QD-QW or QD-QW-QW).
Time to Maximum Plasma Concentration (Tmax) of Setmelanotide After QD Administration in the Run-in Period
时间窗: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose at Week -1
Maximum drug concentration determined directly from individual concentration-time data.
Tmax of Setmelanotide After QW Administration
时间窗: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours postdose at Week 14
Maximum drug concentration determined directly from individual concentration-time data. Data are reported by dose level (treatment regimen) in the OL Period and dosing sequence (QD-QD-QW or QD-QW-QW).
Mean Trough Plasma Concentration (Ctrough) of Setmelanotide After QD or QW Administration at Week 1
时间窗: 30 minutes predose at Week 1
Ctrough is concentration at the end of the dosing interval, prior to subsequent dose administration. Data are reported by dose level (treatment regimen) in the DB Period and dosing sequence (QD-QD-QW or QD-QW-QW).
Mean Setmelanotide Ctrough After QD or QW Administration at Week 5
时间窗: 30 minutes predose at Week 5
Ctrough is concentration at the end of the dosing interval, prior to subsequent dose administration. Data are reported by dose level (treatment regimen) in the DB Period and dosing sequence (QD-QD-QW or QD-QW-QW).
Mean Setmelanotide Ctrough After QD or QW Administration at Week 18
时间窗: 30 minutes predose at Week 18
Ctrough is concentration at the end of the dosing interval, prior to subsequent dose administration. Data are reported by dose level (treatment regimen) in the DB Period and dosing sequence (QD-QD-QW or QD-QW-QW).
Mean Setmelanotide Ctrough After QD or QW Administration at Week 22
时间窗: 30 minutes predose at Week 22
Ctrough is concentration at the end of the dosing interval, prior to subsequent dose administration. Data are reported by dose level (treatment regimen) in the DB Period and dosing sequence (QD-QD-QW or QD-QW-QW).
Mean Setmelanotide Ctrough After QD or QW Administration at Week 9
时间窗: 30 minutes predose at Week 9
Ctrough is concentration at the end of the dosing interval, prior to subsequent dose administration. Data are reported by dose level (treatment regimen) in the DB Period and dosing sequence (QD-QD-QW or QD-QW-QW).
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of Setmelanotide After QD Administration in the Run-in Period
时间窗: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, and 8 hours postdose at Week -1
AUC0-tau was recorded from collected blood samples.
AUC0-tau of Setmelanotide After QD Administration in the Run-in Period
时间窗: Pre-dose (0 hour) and 0.5, 1, 2, 6, 8, 12, 24, 48, 72, 96, 120, and 168-hours postdose at Week 14
AUC0-tau was recorded from collected blood samples. Data are reported by dose level (treatment regimen) in the OL Period and dosing sequence (QD-QD-QW or QD-QW-QW).
Mean Setmelanotide Ctrough After QD or QW Administration at Week 27
时间窗: 30 minutes predose at Week 27
Ctrough is concentration at the end of the dosing interval, prior to subsequent dose administration. Data are reported by dose level (treatment regimen) in the DB Period and dosing sequence (QD-QD-QW or QD-QW-QW).
次要结局
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(From first dose of study drug administration up to Week 30)
- Number of Participants With Injection Site Reactions (ISRs) From Baseline Through Week 13(Baseline through Week 13)
- Number of Participants With ISRs From Week 14 Through Week 27(Week 14 through Week 27)