A Randomized Double-Blind Placebo-Controlled Study of the LEPR Agonist Antibody REGN4461 for the Treatment of Metabolic Abnormalities in Patients With Familial Partial Lipodystrophy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 20
- 试验地点
- 8
- 主要终点
- Percent Change From Baseline to Week 12 in Fasting Serum Triglyceride (TG) (Cohort A)
研究概览
简要总结
Two cohorts are being studied based on leptin levels. Cohort A is composed of patients with baseline leptin <8.0 ng/mL and Cohort B is composed of patients with baseline leptin 8.0 to ≤20.0 ng/mL
The primary objectives will be evaluated for patients in Cohort A only:
- To evaluate the effect of REGN4461 on fasting triglycerides (TG) in patients with elevated baseline fasting TG
- To evaluate the effect of REGN4461 on hyperglycemia in patients with elevated baseline Hemoglobin A1c (HbA1c)
The following secondary objectives of the study will be evaluated for Cohort B and for the combined set of Cohorts A plus B:
- To evaluate the effect of REGN4461 on fasting TG levels in patients with hypertriglyceridemia
- To evaluate the effect of REGN4461 on glycemic control in patients with hyperglycemia
The following secondary objectives of the study will be evaluated for Cohorts A and B separately, and for the combined set of Cohorts A plus B:
- To evaluate the effect of REGN4461 on liver fat in patients with hepatic steatosis
- To evaluate the effect of REGN4461 on hunger
- To evaluate safety and tolerability of REGN4461
- To characterize the concentration profile of REGN4461 over time
- To assess immunogenicity to REGN4461
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of familial partial lipodystrophy as defined in the protocol
- •Fasting leptin level ≤20.0 ng/ml, as determined during the screening period
- •Presence of significant metabolic abnormalities related to glucose and triglycerides (TGs) as defined in the protocol
- •Stable body weight within the 3 months prior to screening (no gain or loss of >5% current weight)
- •Stable diet during the past 3 months defined as no major change in macronutrient composition (eg, starting or stopping diets such as Atkins, Paleo, Vegetarianism, Veganism)
- •No clinically meaningful change in medication regimen in the 3 months prior to screening as defined in the protocol
排除标准
- •Treatment with metreleptin within 3 months of the screening visit
- •Patients with a diagnosis of generalized lipodystrophy
- •Patients with a diagnosis of acquired lipodystrophy
- •Pregnant or breastfeeding women
- •NOTE: Other protocol defined inclusion/exclusion criteria apply
研究组 & 干预措施
Study Arm 1
Randomized to placebo for 12 weeks and then crossover to REGN4461 for 12 weeks
干预措施: REGN4461 (Drug)
Study Arm 1
Randomized to placebo for 12 weeks and then crossover to REGN4461 for 12 weeks
干预措施: Matching Placebo (Drug)
Study Arm 2
Randomized to receive REGN4461 for 24 weeks
干预措施: REGN4461 (Drug)
结局指标
主要结局
Percent Change From Baseline to Week 12 in Fasting Serum Triglyceride (TG) (Cohort A)
时间窗: Baseline to week 12
Percentage change in fasting serum TG was reported for participants with elevated baseline fasting TG (\> 200 mg/dL) and with baseline leptin \< 8.0 ng/mL (Cohort A).
Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) (Cohort A)
时间窗: Baseline to week 12
Change in HbA1c was reported for participants with elevated baseline HbA1c (\> 7.0%) and with baseline leptin \< 8.0 ng/mL (Cohort A).
次要结局
- Percent Change From Baseline to Week 12 in Fasting Serum TG (Cohorts B and A + B)(Baseline to week 12)
- Change From Baseline to Week 12 in HbA1c (Cohorts B and A + B)(Baseline to week 12)
- Percent Change From Baseline to Weeks 12 and 24 in Liver Fat MRI-PDFF (Study Arm 2)(Baseline, Week 12, Week 24)
- Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score(Baseline, Week 12, Week 24)
- Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 1)(Baseline, Week 12, Week 24)
- Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 2)(Baseline, Week 12, Week 24)
- Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 1)(Baseline, Week 12, Week 24)
- Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 2)(Baseline, Week 12, Week 24)
- Concentrations of REGN4461 in Serum(Weeks 0, 1, 2, 3, 4, 5, 6, 9, 12, 13, 14, 15, 16, 17, 18, 21, 28, 32 and 36. Weeks 0 and 12 collected pre- and post-dose. All other time points were only pre-dose.)
- Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 1)(Baseline, Week 12, Week 24)
- Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 2)(Baseline, Week 12, Week 24)
- Percent Change From Baseline to Weeks 12 and 24 in Liver Fat Magnetic Resonance Imaging-derived Proton Density Fat Fraction (MRI-PDFF) (Study Arm 1)(Baseline, Week 12, Week 24)
- Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score(Baseline, Week 12, Week 24)
- Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score(Baseline, Week 12, Week 24)
- Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score(Baseline, Week 12, Week 24)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Up to Day 169)
- Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Response(Up to Day 281)