A Phase 1 Randomized, Double-Blind, Placebo-Controlled, 2-Part Study to Assess the Safety and Tolerability, Pharmacokinetics, And Pharmacodynamics of Single and Multiple Doses of REGN4461 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 113
- 试验地点
- 1
- 主要终点
- Number of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
The primary objective of the study is to evaluate the safety and tolerability of REGN4461 in healthy participants. The secondary objectives of the study are to:
- Characterize the Pharmacokinetic (PK) profile of single and repeated doses of REGN4461 and evaluate the effects of baseline covariates on PK profile
- Estimate the effects of repeated doses of REGN4461 on body weight over 12 weeks in overweight and obese participants
- Assess the effects of repeated doses of REGN4461 on ad lib energy intake in overweight and obese participants
- Evaluate the effects of single and repeated doses of REGN4461 on soluble forms of lipid-regulating proteins levels over time
- Assess the immunogenicity of single and repeated doses of REGN4461
详细描述
This is a 2-part study of the safety, tolerability, PK and pharmacodynamic (PD) of single and repeated doses of REGN4461 in healthy participants. In Part A, healthy lean or overweight participants will be enrolled to evaluate the safety, tolerability, PK, and PD of single ascending intravenous (IV) and subcutaneous (SC) doses. Interim PK and safety information from Part A will be used to select the dose level, frequency, and mode of administration (IV or SC) for repeat dosing in Part B. In Part B, overweight/obese participants with body mass index (BMI) 25-40 kg/m2 will be enrolled to evaluate the safety, tolerability, PK, and PD of repeated doses of REGN4461 in 4 distinct cohorts defined by baseline leptin levels.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Part A: Single dose cohort 1
Cohort 1 will receive a single IV dose of REGN4461 or matching placebo
干预措施: REGN4461 (Drug)
Part A: Single dose cohort 1
Cohort 1 will receive a single IV dose of REGN4461 or matching placebo
干预措施: Placebo (Drug)
Part A: Single dose cohort 2
Cohort 2 will receive a sequential ascending single IV dose of REGN4461 or matching placebo
干预措施: REGN4461 (Drug)
Part A: Single dose cohort 2
Cohort 2 will receive a sequential ascending single IV dose of REGN4461 or matching placebo
干预措施: Placebo (Drug)
Part A: Single dose cohort 3
Cohort 3 will receive a sequential ascending single IV dose of REGN4461 or matching placebo
干预措施: REGN4461 (Drug)
Part A: Single dose cohort 3
Cohort 3 will receive a sequential ascending single IV dose of REGN4461 or matching placebo
干预措施: Placebo (Drug)
Part A: Single dose cohort 4
Cohort 4 will receive a sequential ascending single SC dose of REGN4461 or matching placebo
干预措施: REGN4461 (Drug)
Part A: Single dose cohort 4
Cohort 4 will receive a sequential ascending single SC dose of REGN4461 or matching placebo
干预措施: Placebo (Drug)
Part A: Single dose cohort 5
Cohort 5 will receive a sequential ascending single IV dose of REGN4461 or matching placebo
干预措施: REGN4461 (Drug)
Part A: Single dose cohort 5
Cohort 5 will receive a sequential ascending single IV dose of REGN4461 or matching placebo
干预措施: Placebo (Drug)
Part A: Single dose cohort 6
Cohort 6 will receive a sequential ascending single SC dose of REGN4461 or matching placebo
干预措施: REGN4461 (Drug)
Part A: Single dose cohort 6
Cohort 6 will receive a sequential ascending single SC dose of REGN4461 or matching placebo
干预措施: Placebo (Drug)
Part A: Single dose cohort 7
Cohort 7 will receive a sequential ascending single IV dose of REGN4461 or matching placebo
干预措施: REGN4461 (Drug)
Part A: Single dose cohort 7
Cohort 7 will receive a sequential ascending single IV dose of REGN4461 or matching placebo
干预措施: Placebo (Drug)
Part A: Single dose cohort 8
Cohort 8 will receive a single IV dose of REGN4461 or matching placebo
干预措施: REGN4461 (Drug)
Part A: Single dose cohort 8
Cohort 8 will receive a single IV dose of REGN4461 or matching placebo
干预措施: Placebo (Drug)
Part A: Single dose cohort 9
Cohort 9 will receive a single IV dose of REGN4461 or matching placebo
干预措施: REGN4461 (Drug)
Part A: Single dose cohort 9
Cohort 9 will receive a single IV dose of REGN4461 or matching placebo
干预措施: Placebo (Drug)
Part B: Repeated dose cohort 10
Cohort 10 will receive repeated IV or SC doses of REGN4461 or matching placebo
干预措施: REGN4461 (Drug)
Part B: Repeated dose cohort 10
Cohort 10 will receive repeated IV or SC doses of REGN4461 or matching placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Number of treatment-emergent adverse events (TEAEs)
时间窗: Up to week 27
次要结局
- Percent change from baseline to week 12 in body weight in overweight or obese participants(Baseline to week 12)
- Absolute change from baseline to week 12 in body weight in overweight or obese participants(Baseline to week 12)
- PK parameter: clearance (CL)(Up to week 27)
- Concentrations of REGN4461 in serum over time(Up to week 27)
- Pharmacokinetic (PK) parameter: Area under curve (AUC) computed from time zero to the time of the last positive concentration (AUClast)(Up to week 27)
- PK parameter: trough concentration (Ctrough)(Up to week 27)
- Incidence of anti-drug antibodies to REGN4461 over time after single doses of REGN4461(Up to week 16)
- Incidence of anti-drug antibodies to REGN4461 over time after repeated doses of REGN4461(Up to week 27)
- PK parameter: AUC computed across a dosing interval with length τ (AUCo-τ)(Upt to week 27)
- PK parameter: peak concentration (Cmax)(Up to week 27)
- PK parameter: time to Cmax (tmax)(Up to week 27)
- Change from baseline in caloric intake in response to standardized meals in overweight or obese participants(Baseline to week 12)
- Change in lipid-regulating protein levels over time after single doses of REGN4461(Up to week 16)
- Change in lipid-regulating protein levels over time after repeated doses of REGN4461(Up to week 27)