Safety, Tolerability and PK/PD of RB006 in a Healthy Volunteer SAD (SC101)
A Phase 1 Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RB006 Administered Subcutaneously, With and Without IV RB007, in Healthy Young Volunteers
This was a Phase 1a, single-center, double-blind, randomized, placebo-controlled study of the safety, tolerability, PK, and PD of single ascending doses of RB006 administered as an SC injection, with and without IV RB007 (an active control agent for RB006), in healthy young volunteers. The study originally planned to enroll 4 cohorts of 8 subjects each (N=32); however, upon review cohort (Cohort 1-A) was necessary in order to fully define the PK profile of SC RB006. Therefore, 36 subjects were enrolled in this study.
Each cohort was balanced by sex with no more than 2/3 of one sex enrolled in any particular cohort (i.e., 5 of 8 subjects in each cohort). No subject participated in >1 dose group, and progression to the next higher dose only occurred if the prior dose level was well tolerated, as assessed by a Safety Review Committee (SRC)
研究概览
地位
条件
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
-
-
Texas
-
Austin、Texas、美国、78744
- PPD Development, LP
-
-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- An Institutional Review Board (IRB)-approved informed consent was signed and dated prior to any study-related activities.
- Subject was between the ages of 18 and 45 years, inclusive.
- Subject was a female with a negative urine or serum pregnancy test or postmenopausal for at least 1 year prior to randomization.
- Subject had a body mass index (BMI) between 18 kg/m2 and 32 kg/m2 (weight/[height]2) and was ≥50 kg and ≤120 kg total body weight.
- Subject had normal (or abnormal and clinically insignificant) laboratory values at Screening.
- Subject was medically normal with no significant abnormal findings at the Screening physical examination.
- Subject had the ability to understand the requirements of the study and a willingness to comply with all study procedures.
- Subject had not consumed and agreed to abstain from taking any dietary supplements or nonprescription drugs
- Subject had not consumed and agreed to abstain from taking any prescription drugs
- Subject had not consumed alcohol-containing beverages for 3 days prior to CRU admission
- Subject had not consumed grapefruit or grapefruit juice within the 14 days prior to CRU admission
- Subject had not used tobacco or nicotine-containing products within 6 months prior to CRU admission
Exclusion Criteria:
- Evidence or history of clinically significant oncologic, pulmonary, hepatic, gastrointestinal (GI), cardiovascular, hematologic, metabolic, neurological, immunologic, nephrologic, endocrine, or psychiatric disease.
- Any evidence or history of intracranial bleeding, aneurysm, or thrombotic or hemorrhagic stroke.
- Any known individual or family history of a bleeding diathesis or coagulopathy.
- Active or expected menstruation during the Treatment Phase (females only).
- History of thrombocytopenia associated with abnormal bleeding or risk of a bleeding event, or screening or baseline platelet count <100,000/mm3.
- History of thrombocytosis associated with a thrombotic event or risk for a thrombotic event, or screening or baseline platelet count >600,000/mm3.
- Endoscopically confirmed peptic ulcer disease within 3 years of CRU admission or GI bleeding within 3 months of CRU admission, including a positive stool for occult blood at Screening or Baseline.
- Urinary tract bleeding within 3 months of CRU admission, including microscopic hematuria on screening or baseline urinalysis.
- Unusual or prolonged bleeding (e.g., gum bleeding, nosebleeds, easy bruising), as documented on the Self-Reported Bleeding Questionnaire, at Screening.
- Severe trauma, fracture, major surgery, or biopsy of a parenchymal organ within 3 months of CRU admission.
- Severe persistent hypertension (systolic pressure >180 mmHg or diastolic pressure >110 mmHg).
- Baseline hemoglobin <12.0 g/dL for males or <11.0 g/dL for females; prothrombin time (PT) greater than the ULN; or aPTT greater than the ULN.
- Clinically significant liver dysfunction (e.g., as evidenced by elevated liver function tests).
- Clinically significant renal dysfunction (e.g., estimated glomerular filtration rate <60 mL/min or serum creatinine >1.5 mg/dL).
- History of illicit drug abuse in the past year or current evidence of such abuse in the opinion of the Investigator.
- Positive findings on urine drug screen.
- Positive findings for human immunodeficiency virus, hepatitis B, and/or hepatitis C at Screening.
- Pregnant or lactating.
- Acute illness within 1 week of CRU admission.
- A history of alcohol abuse in the past year relative to CRU admission.
- Donated plasma within 7 days of study drug administration.
- Donated 1 or more pints of blood (or equivalent blood loss) within 6 weeks prior to study drug administration.
- Use of an investigational drug within 30 days prior to CRU admission or prior REG1 Anticoagulation System exposure.
学习计划
研究是如何设计的?
设计细节
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:四人间
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
其他:Cohort 1
Cohort 1: 6 subjects received Subcutaneous RB006 0.5 mg/kg and 2 subjects received SC placebo
|
安慰剂
其他名称:
Subcutaneous RB006 0.5 mg/kg
其他名称:
|
其他:Cohort 1-A
Cohort 1-A: 4 subjects received open-label Subcutaneous RB006 0.5 mg/kg
|
Subcutaneous RB006 0.5 mg/kg
其他名称:
|
其他:Cohort 2
Cohort 2: 6 subjects received Subcutaneous RB006 1.0 mg/kg and 2 subjects received SC placebo
|
安慰剂
其他名称:
Subcutaneous RB006 1.0 mg/kg
其他名称:
|
其他:Cohort 3
Cohort 3: 6 subjects received Subcutaneous RB006 3.0 mg/kg and 2 subjects received SC placebo
|
安慰剂
其他名称:
Subcutaneous RB006 3.0 mg/kg
其他名称:
|
其他:Cohort 4
8 subjects received subcutaneous RB006 2.0 mg/kg as well as the following:
|
其他名称:
|
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
Primary Outcome of this study using SC RB006 with and without RB007 in healthy volunteers was safety as determined by Treatment Emergent Adverse Events
大体时间:10 days
|
10 days
|
次要结果测量
结果测量 |
大体时间 |
---|---|
Outcome of this study using SC RB006 with and without RB007 in healthy volunteers was safety as determined by Serious Adverse Events
大体时间:10 days
|
10 days
|
Outcome of this study using SC RB006 with and without RB007 in healthy volunteers was pharmacodynamics as determined by change from baseline in aPTT
大体时间:Pre-dose, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216 (and if applicable, 264) hours post RB006 dose
|
Pre-dose, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216 (and if applicable, 264) hours post RB006 dose
|
Outcome of this study using SC RB006 with and without RB007 in healthy volunteers was pharmacokinetics as determined by Maximum Observed Plasma Concentration (Cmax)
大体时间:Pre-dose, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 48, 60, 72, 84, 96, 120, 144, 168, and 216 (and if applicable, 264) hours post-RB006 dose
|
Pre-dose, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 48, 60, 72, 84, 96, 120, 144, 168, and 216 (and if applicable, 264) hours post-RB006 dose
|
合作者和调查者
调查人员
- 首席研究员:Matthew M Medlock, MD、PPD
出版物和有用的链接
一般刊物
- Park EJ, Choi J, Lee KC, Na DH. Emerging PEGylated non-biologic drugs. Expert Opin Emerg Drugs. 2019 Jun;24(2):107-119. doi: 10.1080/14728214.2019.1604684. Epub 2019 Apr 19.
- Vavalle JP, Rusconi CP, Zelenkofske S, Wargin WA, Alexander JH, Becker RC. A phase 1 ascending dose study of a subcutaneously administered factor IXa inhibitor and its active control agent. J Thromb Haemost. 2012 Jul;10(7):1303-11. doi: 10.1111/j.1538-7836.2012.04742.x.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他研究编号
- REG1-CLINSC101
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
安慰剂的临床试验
-
City of Hope Medical CenterNational Cancer Institute (NCI)主动,不招人造血和淋巴细胞肿瘤 | 骨髓纤维化 | 慢性淋巴细胞白血病 | 缓解期成人急性髓性白血病 | 骨髓增生异常综合症 | 缓解期成人急性淋巴细胞白血病 | 骨髓增殖性肿瘤 | 慢性期慢性粒细胞白血病,BCR-ABL1 阳性 | 成人淋巴母细胞淋巴瘤 | 加速期慢性粒细胞白血病,BCR-ABL1 阳性 | HLA-A*0201 阳性细胞存在 | 巨细胞病毒感染 | 成人霍奇金淋巴瘤 | 成人非霍奇金淋巴瘤美国
-
Mila (bMotion Technologies)完全的
-
Universidad Autonoma de MadridCentro Universitario La Salle完全的