Phase I/II, Open-Label Study to Determine Safety and Efficacy of Sotatercept (ACE-011) in Adults With Red Blood Cell Transfusion- Dependent Diamond Blackfan Anemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Number of Participants With Complete Response and Partial Response
研究概览
简要总结
The purpose of this study is to determine the safety and dosing of drug Sotatercept, as a subcutaneous injection, to stimulate production of red blood cell production. To be given every 28 days for up to four doses.
详细描述
This study is for adult patients with Diamond Blackfan Anemia who are currently being transfused every 3- 4 weeks.
The drug will be given as a subcutaneous injection within one of three dose levels. The first dose level (0.1 mg/kg) will include 3 subjects who will receive the same dose of the drug monthly for a total of 4 doses, as long as there are no dose- limiting toxicities (DLTs). A Dose limiting toxicity is defined as inability to deliver the scheduled doses because of toxicity >/= Grade 3, according to NCI Toxicity Grading Scale.
Once all 3 subjects have received and tolerated the low dose level, the next level will open (0.3 mg/kg)to 3 new subjects. Subjects will be monitored closely for response and side effects.
If more than 2 subjects have a dose limiting toxicity in the first dose level, then dose level -1 (0.05 mg/kg)will open, enrolling 3 more subjects. If more than 2 subjects at dose level -1, have dose limiting toxicities, the study will be discontinued. If there are no additional dose limiting toxicities, dose level -1 will be the maximum tolerated dose.
There are a total of 3 dose levels, not including dose level -1. Once the maximum tolerated dose has been reached, up to a total of 10 additional subjects will be enrolled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •>/= 18 years of age
- •DBA diagnosed
- •RBC transfusion- dependence (defined as >/= 10 cc/kg of RBC per 28 days average)
- •Karnofsky performance scale >/= 70
- •Females of childbearing potential are to use birth control during study participation and for 112 days following the last dose of sotatercept
- •Males must agree to use a latex condom during any sexual contact with females of childbearing potential while participating in the study and for 112 days following the last dose of sotatercept
- •Agreement to adhere to the study visit schedule, understand and comply with all protocol requirements
- •Understand and sign a written informed consent
排除标准
- •Creatinine clearance < 30 ml/min
- •SGOT > 3x upper limit of normal, SGPT > 3x upper limit normal, or bilirubin >3x upper limit normal
- •Heart disease (NY Heart Association classification of >/= 3
- •History of hypertension
- •Subjects currently responsive to corticosteroids for treatment of Diamond Blackfan anemia
- •Treatment with another investigational drug or device <56 days pre-study entry
- •Pregnant or lactating females
研究组 & 干预措施
Sotatercept
Sotatercept to be given as a subcutaneous injection once a month for 4 consecutive months, using a dose escalation scale among 3 cohorts. *Protocol Amendment: Two additional cohorts will be given Sotatercept 0.75mg/kg and 1 mg/kg as a subcutaneous injection once every 3 weeks.
干预措施: Sotatercept (Drug)
Sotatercept with prednisone boost
Protocol Amendment: Two additional cohorts will be given Sotatercept 0.75mg/kg and 1 mg/kg as a subcutaneous injection once every 3 weeks along with a prednisone boost of 1 mg/kg daily for 3 weeks (max of 60 mg).
干预措施: Sotatercept with prednisone boost (Drug)
结局指标
主要结局
Number of Participants With Complete Response and Partial Response
时间窗: 9 months
Complete response is transfusion independence with hemoglobin \>9 gm/dl; partial response is transfusion dependence with hemoglobin \< 9gm/dl with an increase in reticulocyte count over baseline
次要结局
- Severe Adverse Events Attributable to Study Drug(9 months)
研究者
Adrianna Vlachos, MD
Principal Investigator
Northwell Health