NCT02216084已完成1 期
BAX930 (rADAMTS13): A Phase 1 Prospective, Uncontrolled, Open-Label, Multicenter, Dose-Escalation Study Evaluating the Safety and Pharmacokinetics in Hereditary Thrombotic Thrombocytopenic Purpura (TTP)
Baxalta now part of Shire11 个研究点 分布在 7 个国家目标入组 16 人开始时间: 2014年9月30日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 11
- 主要终点
- Occurrence of adverse events (serious and non-serious), including the incidence of binding and inhibitory antibody formation
研究概览
简要总结
The purpose of this Phase 1, prospective, uncontrolled, open-label, multicenter, dose-escalation study is to evaluate the safety, including immunogenicity, and pharmacokinetics of BAX930 (rADAMTS13) in a total of 14 evaluable subjects diagnosed with severe hereditary thrombotic thrombocytopenic purpura (TTP) (plasma ADAMTS13 activity <6%) who are assigned to one of three dose cohorts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject is between 12 and 65 years of age, inclusive. (The first 2 subjects in any cohort will be ≥ 18 years of age.)
- •Subject and/or legally authorized representative has provided written informed consent.
- •Subject has a documented diagnosis of severe hereditary ADAMTS13 deficiency, defined as 1) confirmed by genetic testing, documented in patient history or at screening, and 2) ADAMTS13 activity < 6%, documented in patient history or at screening. NOTE: In patients receiving prophylactic therapy with fresh frozen plasma (FFP) or other ADAMTS13 containing products, the levels of plasma ADAMTS13 activity may exceed 6% at screening.
- •Cryoprecipitate, FFP, or other ADAMTS13 containing products interfering with ADAMTS13 PK have to be paused at least 10 days prior to infusion of the investigational product.
- •The subject is not displaying any severe TTP symptoms at screening. Patients presenting with minor, but stable laboratory abnormalities (LDH not higher than 3 times the upper limit of normal; platelet count not lower than 100,000 per μl) at screening may be enrolled.
- •Subjects ≥18 years of age have a Karnofsky score ≥ 60%, and subjects < 18 years of age have a Lansky score ≥ 70%.
- •Subject is hepatitis C virus negative (HCV-) as confirmed by antibody or polymerase chain reaction (PCR) testing; HCV positive (HCV+) subjects are eligible for inclusion if their disease is chronic but stable.
- •If female of childbearing potential, subject presents with a negative serum pregnancy test and agrees to employ adequate birth control measures for the duration of the study.
- •Subject is willing and able to comply with the requirements of the protocol.
排除标准
- •Subject has been diagnosed with any other TTP-like disorder (for example, microangiopathic hemolytic anemia), including acquired TTP.
- •Subject has known hypersensitivity to hamster proteins or other components of the investigational product.
- •Subject has a medical history or presence of a functional neutralizing ADAMTS13 inhibitor at screening.
- •Subject has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis/mild asthma, food allergies or animal allergies.
- •Subject has a medical history of hematological disorders, in particular systemic lupus erythematosus, amyloidosis, antiphospholipid antibody syndrome, vasculitis, other hemolytic anemia, disseminated intravascular coagulation, and systemic scleroderma.
- •Subject has a history of significant neurological events, such as major stroke, indicating that a relapse might have severe consequences, as judged by the investigator.
- •Subject is HIV positive with an absolute CD4 count < 200/mm
- •Subject has been diagnosed with a cardiovascular disease [New York Heart Association (NYHA) classes 3-4].
- •Subject is scheduled to undergo elective surgery during study participation.
- •Subject has been diagnosed with severe liver disease, as evidenced by, but not limited to, any of the following: serum ALT 3 times the upper limit of normal, international normalized ratio (INR) > 1.5, hypoalbuminemia, portal vein hypertension (e.g. presence of otherwise unexplained splenomegaly, history of esophageal varices).
- •Subject has been diagnosed with severe glomerular disease, with gross proteinuria and a serum creatinine level ≥ 2.5 mg/dL.
- •Subject has been treated with an immunomodulatory drug, in case of corticoids with an equivalent to hydrocortisone greater than 10 mg /day, excluding topical treatment (e.g. ointments, nasal spray), within 30 days prior to enrollment.
- •Subject has a history of drug and/or alcohol abuse within the last 6 months prior to study enrollment.
- •Subject has a life expectancy of less than 3 months.
- •Subject is identified by the investigator as being unable or unwilling to cooperate with study procedures.
- •Subject is a family member or employee of the investigator.
- •Subject suffers from a mental condition rendering him/her unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude.
- •If female, subject is pregnant or lactating at the time of study enrollment.
- •Subject has participated in another clinical study involving an investigational product or device within 30 days prior to study enrollment.
- •Subject is scheduled to participate in another clinical study involving an investigational product or device during the course of this study.
研究组 & 干预措施
Recombinant ADAMTS13
Experimental
The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 3 subjects; Cohort 2: 3 subjects; Cohort 3: 8 subjects]. Subjects will be enrolled and dosed sequentially. Subjects will be recruited to the next dose level only after short-term safety has been demonstrated and reviewed by an independent Data Monitoring Committee (DMC) at the preceding dose level. The first 2 subjects in any cohort will be ≥ 18 years of age. The effects of the investigational product on vital signs, hematology, and clinical chemistry parameters (up to 96 ± 2 hrs blood sampling timepoint) will determine short-term safety. The DMC will recommend whether to proceed with the study or in case of a safety concern recommend remedial actions and/or to discontinue the study. Subject participation will continue until 28 ± 3 days after infusion of the investigational product. Subject participation in one Dose Cohort (1-3) is expected to be approximately 6-8 weeks.
干预措施: Recombinant ADAMTS13 (Drug)
结局指标
主要结局
Occurrence of adverse events (serious and non-serious), including the incidence of binding and inhibitory antibody formation
时间窗: Up to 28 (± 3) days after investigational product infusion
次要结局
- Pharmacokinetic [PK] parameter 'incremental recovery [IR]'(Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion)
- PK parameter 'maximum concentration following infusion [Cmax]'(Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion)
- PK parameter 'minimum time to reach Cmax [T max]'(Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion)
- PK parameter 'terminal or disposition half-life [T1/2]'(Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion)
- PK parameter 'mean residence time [MRT]'(Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion)
- PK parameter 'systemic clearance [Cl]'(Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion)
- PK parameter 'area under the plasma/time curve [AUC]'(Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion)
- PK parameter 'steady state volume of distribution [Vss]'(Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion)
- Plasma von Willebrand factor: Ristocetin cofactor activity [VWF:RCo], von Willebrand factor antigen [VWF:Ag] and VWF structure analysis(Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion)
研究者
研究点 (11)
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