A Phase 2a, Multi-center, Randomized, Single Dose, Double-blind, Placebo-controlled Followed by a Multiple-dose, Single-blind, Placebo-controlled, Dose Escalation Study to Evaluate the Pharmacokinetics, Safety, Efficacy, Tolerability, and Pharmacodynamics of Sotatercept (ACE-011) for the Correction of Anemia in Subjects With End-stage Renal Disease (ESRD) on Hemodialysis (HD).
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 50
- 试验地点
- 48
- 主要终点
- AUCinf: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity
研究概览
简要总结
This is the first study in hemodialysis subjects with anemia to evaluate the pharmacokinetics, safety, efficacy, tolerability, and pharmacodynamics of sotatercept (ACE-011)
详细描述
Part 1:
Approximately 8 subjects will be randomized to receive either a single 0.1 mg/kg subcutaneous dose of sotatercept or matching placebo in a 3:1 ratio
Part 2:
Approximately 8 subjects will be randomized to each of the 3 sequential dose groups (0.3mg/kg or 0.5mg/kg or 0.7 mg/kg) with a 3:1 ratio of sotatercept or placebo (6 subjects in the sotatercept arm and 2 in the placebo arm). A total of 24-36 subjects may be randomized in the 3 dose groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Single (Participant)
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
- •Males or females ≥18 years of age.
- •Subjects on hemodialysis for at least 12 weeks before screening
- •Subjects on a stable dose of Erythrocyte Stimulating Agents product to maintain Hemoglobin (Hb) for at least 6 weeks prior to screening.
- •3 consecutive pre-dialysis Hb concentrations with a mean ≥10 to ≤ 12 g/dL (≥100 to ≤120 g/L) at screening and one pre-dialysis Hb concentration ≥8 to < 10 g/dL (≥ 80 to < 100 g/L) before randomization.
- •Adequate iron status defined as serum transferrin saturation ≥ 20% before randomization.
排除标准
- •Non renal causes of anemia.
- •Subjects on peritoneal dialysis.
- •Systemic hematological disease
- •High sensitivity C-reactive protein >50mg/L at screening.
- •Alanine transaminase (ALT) or aspartate transaminase (AST) laboratory values > 2 times the upper limit of normal (ULN) at screening.
- •Uncontrolled diabetes mellitus (HbA1c > 9) at screening.
- •Uncontrolled hypertension.
- •Red Blood Count (RBC) transfusions within 8 weeks prior to screening.
- •Active serious infection or history of recurrent serious infection likely to recur during the study
- •History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product or to the iron products needed to normalize iron levels for subjects.
- •Subjects that received treatment with another investigational drug or device within 28 days prior to Day 1
- •Pregnant or lactating females.
研究组 & 干预措施
Placebo
The Placebo to Sotatercept ratio is 1:3 meaning for every 1 patient that receives Placebo, 3 patients will receive Sotatercept.
干预措施: Placebo (Biological)
结局指标
主要结局
AUCinf: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity
时间窗: From first dose up to Day 28
Area under the concentration-time curve from time zero extrapolated to infinity. Only Part 1 pharmacokinetic evaluable participants were pre-specified to be evaluated in this endpoint.
Apparent Total Clearance (CL/F)
时间窗: From first dose up to Day 28
Apparent Total Clearance (CL/F) is defined as the volume of plasma from which the study drug is completely removed per unit of time. It is equal to the drug dose divided by the area-under-the-curve.
Apparent Volume of Distribution Based on Terminal Phase (Vz/F)
时间窗: From first dose up to Day 28
Apparent volume of distribution based on terminal phase (Vz/F) is defined as the apparent volume in which the current amount of drug in the body must be dispersed in order to give the current plasma concentration. Apparent volume of distribution is important for determining the dose required to produce a desired plasma concentration of the drug.
Observed Maximum Concentration (Cmax)
时间窗: From first dose up to Day 28
Cmax is a pharmacokinetic parameter defined as the observed maximum concentration of the study drug in the serum and/or blood. Cmax will be estimated from the sotatercept concentration versus time data using noncompartmental method.
Time to Maximum Concentration (Tmax)
时间窗: From first dose up to Day 28
Time to observed maximum concentration (Tmax) is defined as the amount of time in days for a drug to reach the maximum concentration after administration.
Area Under Curve (AUC)-28 Days
时间窗: From first dose up to Day 28
AUC-28 days is defined as area under the concentration-time curve over the first 28-day dosing interval
Terminal Half-Life (t1/2,z)
时间窗: Days 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 85 and 113
Terminal plasma half-life (t1/2,z) is the time taken for concentration of the study drug to decrease from its maximum concentration (Cmax) to half of Cmax in the blood plasma.
次要结局
- The Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)(From first dose up to 115 days post last dose)
- Number of Participants With Hemoglobin > 12g/dL(Pre-dose; Dose 1-Days 1, 8, 15, 22, 29; Doses 2, 3, 4, 5, 6, 7-Days 1, 15, 29; Follow-up Phase Days 225, 253, 281, and 309)
- Blood Pressure Changes From Baseline(From pre-dose up to the final visit 112 days after last dose (up to 225 days))
- Changes in Follicle Stimulating Hormone (FSH)(Day 1 (baseline), Day 15, Day 29, and Day 113)
- Number of Participants With Change From Baseline Hemoglobin ≥ 1g/dL(Pre-dose; Dose 1-Days 1, 8, 15, 22, 29; Doses 2, 3, 4, 5, 6, 7-Days 1, 15, 29; Follow-up Phase Days 225, 253, 281, and 309)
- Change From Baseline in Hemoglobin Values(From first dose up to Day 225)
- Proportion of Participants With Rise in Hemoglobin > 2 g/dL During 4 Week Period(Pre-dose; Dose 1-Days 1, 8, 15, 22, 29; Doses 2, 3, 4, 5, 6, 7-Days 1, 15, 29; Follow-up Phase Days 225, 253, 281, and 309)
- Number of Participants With Hemoglobin > 10g/dL and Change From Baseline Hemoglobin ≥ 1g/dL(Pre-dose; Dose 1-Days 1, 8, 15, 22, 29; Doses 2, 3, 4, 5, 6, 7-Days 1, 15, 29; Follow-up Phase Days 225, 253, 281, and 309)
- Length of Time to Rescue Therapy(From first dose up to blood transfusion or ESA therapy, up to approximately 209 days)
- Number of Participants With Hemoglobin > 10g/dL(Pre-dose; Dose 1-Days 1, 8, 15, 22, 29; Doses 2, 3, 4, 5, 6, 7-Days 1, 15, 29; Follow-up Phase Days 225, 253, 281, and 309)