NCT04580407已完成2 期
A Phase 2/3, Open-Label, Non-controlled Study to Evaluate the Efficacy and Safety of B-Domain Deleted Recombinant Porcine Factor VIII (rpFVIII, TAK-672), in the Treatment of Serious Bleeding Episode in Japanese Subjects With Acquired Hemophilia A (AHA)
Takeda9 个研究点 分布在 1 个国家目标入组 5 人开始时间: 2021年4月9日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 5
- 试验地点
- 9
- 主要终点
- Percentage of Participants With Severe Bleeding Episodes Who Demonstrated Response to TAK-672 Therapy at 24 Hours After the Initiation of Treatment
研究概览
简要总结
The main aims of the study are to learn if TAK-672 can control bleeds in participants with acquired hemophilia A and if the participants have side effects from TAK-672. Acquired hemophilia A is when people's immune system attacks specific proteins, known as clotting factors, in their bodies. This is different from hemophilia A, which is a condition people are born with.
At the first visit, the study doctor will check who can take part. For those who can take part, participants will visit the clinic or hospital when they get their next bleed. They will receive TAK-672 slowly through a vein. This is called an infusion. They might need extra infusions of TAK-672 to control the bleed. After their bleed is controlled, participants will regularly visit the clinic for a check-up and to treat any further bleeds. This will happen until all participants have received their last dose of TAK-672 to control their 1st bleed. After this, all participants will visit the clinic 90 days later for a final check-up.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female Japanese participants of >=18 years of age.
- •Participants who (or their legally authorized representatives) have provided his/her written informed consent form prior to any study-related procedures and study product administration.
- •Participants with a diagnosis of AHA based on clinical evaluation and supportive local laboratory testing as shown below:
- •Presentation with spontaneous bleeding without anatomical cause and without prior known bleeding disorder.
- •Prolonged activated partial thromboplastin time (aPTT) without explanation.
- •Abnormal aPTT cross mixing test consistent with FVIII inhibitors
- •Confirmation of a low FVIII:C.
- •Positive FVIII inhibitor (>=0.6 BU) as measured either in the local or central laboratory
- •Participants with a severe bleeding episode which the investigator finds necessary to treat and whose severe bleeding episode meets at least 1 of the following criteria:
- •Bleeds that pose a threat to a vital organ that could threaten life (e.g. intracranial bleed, or any site that could obstruct the airway).
- •Bleeds that pose a threat to a vital organ where life is not threatened but the organ function could be impaired (e.g., intraspinal bleed threatening the spinal cord and/or nerve conduction; a continual bleed into the kidney or bladder that could result in an obstructive uropathy, testicular bleed, bleed in and around the eye).
- •Bleeds requiring a blood transfusion to maintain the Hgb level at above-life or organ threatening levels (e.g. post-surgical, gastro-intestinal, retro-peritoneal, and thigh bleeds).
- •Intramuscular bleeds where muscle viability and/or neurovascular integrity is significantly compromised or at risk of being compromised.
- •Intra-articular bleeds impacting a major joint associated with severe pain, swelling and severe loss of joint mobility (reduced >70%) or where a bleed could result in joint destruction (e.g. in and around the femoral head).
- •Participants who are taking anti-thrombotics (including anti-platelet agents and anticoagulantswith confirmatory laboratory testing documenting specific FVIII inhibitor titer and with 3 half-lives of the agent have elapsed since the last dose.
- •Participants with expected life expectancies of at least 90 days prior to the onset of the hemorrhagic episode.
- •Participants of reproductive age who have agreed to use acceptable methods of contraception and if female, undergo pregnancy testing as part of the screening process.
- •Participant who are able to willing and able to comply with the requirements of the protocol.
排除标准
- •Participants with an established reason for bleeding that is not correctable even with hemostatic therapy.
- •Participants presenting a bleeding episode that is assessed likely to resolve on its own, even if left untreated.
- •Participants with a known major sensitivity (anaphylactoid reactions) to therapeutic products of porcine or hamster origin; examples include therapeutics of porcine origin (e.g. previously marketed porcine FVIII, Hyate: C) and recombinant therapeutics prepared from hamster cells (e.g. Humira, Advate, and Enbrel).
- •Participants with the use of hemophilia medication: prior to the administration of TAK-672 under one of the following conditions: (1) use of "recombinant activated factor VII (rFVI)Ia " within 3 hours prior to TAK-672 administration (2) use of " activated prothrombin complex concentrate (aPCC)" within 6 hours prior to TAK-672 administration or (3) use of " plasma-derived FX/FVIIa complex concentrate (pd-FX/FVIIa) " within 8 hours prior to TAK-672 administration.
- •Participants with an anticipated need for treatment or device during the study that may interfere with the evaluation of the safety or efficacy of TAK-672, or whose safety or efficacy may be affected by TAK-
- •Participants who are currently pregnant or breastfeeding, or planning to become pregnant or father a child during the study
- •Participants who have participated in another clinical study and has been exposed to an investigational product or device within 30 days prior to the study enrollment.
- •Participants who are scheduled to participate in another non-observational (interventional) clinical study involving an investigational product or device during the course of the study.
- •Participants who are unable to or unwilling to comply with the study design, protocol requirements, and/or the follow-up procedures.
- •Participants whose majority of age are under legal protection.
- •Participants who are an immediate family member, study site employee, or are in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g. spouse, parent, child, sibling) or may consent under duress.
- •Participants who are judged by the investigator as being ineligible for any other reason.
研究组 & 干预措施
TAK-672
Experimental
TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
干预措施: TAK-672 (Biological)
结局指标
主要结局
Percentage of Participants With Severe Bleeding Episodes Who Demonstrated Response to TAK-672 Therapy at 24 Hours After the Initiation of Treatment
时间窗: 24 hours after the initial dose of TAK-672
Percentage of severe bleeding episodes with demonstrated response to TAK-672 therapy at 24 hours after the initiation of treatment was assessed by using a well-defined 4-point ordinal scale - A 'positive response' was defined as 'effective' (bleeding stopped with clinical control and FVIII:C levels of 50% or higher ) or 'partially effective' (bleeding reduced with clinical stabilization and FVIII:C levels of 20% or higher) control of bleeding, as determined by the investigator using a 4-point rating scale (effective - partially effective - poorly effective - not effective). 'Poorly effective' was defined as 'bleeding slightly reduced or unchanged and FVIII:C levels of less than 50%'. 'Not effective' was defined as 'bleeding worsening and FVIII:C levels of less than 20%'.
次要结局
- Percentage of Participants With Severe Bleeding Episodes Successfully Controlled With TAK-672 Therapy, as Assessed by the Investigator(From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum))
- Percentage of Participants With Bleeding Episodes Responsive to TAK-672 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator(At 0.5, 8, 16, 24, 48, 60, 96, and 120 hours post dose and at 1, 14, 28, 42, 56, 70, and 90 day follow-up)
- Frequency of Infusions Per Participant of TAK-672 Required to Successfully Control Qualifying Bleeding Episodes(From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum))
- Total Dose of Infusions Per Participant of TAK-672 Required to Successfully Control Qualifying Bleeding Episodes(From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum))
- Total Number of Infusions Per Participant of TAK-672 Required to Successfully Control Qualifying Bleeding Episodes(From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum))
- Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes(At 0.5, 8, 16, 24, 48, 60, 96,120, and 144 hours post dose and at 1, 14, 28, 42, 56, 70, and 90 day follow-up)
- Mean Value of Pre-infusion Anti-TAK-672 Antibody Titers in Participants With Successful Control of the Bleeding Episode(From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum))
- Mean Value of Total Dose Per Participant in Participants With Successful Control of the Bleeding Episode(From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum))
- Number of Participants With Positive Response at 24 Hours After the Initiation of Treatment in Participants With Successful Control of the Bleeding Episode(From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum))
- Anti-hFVIII Inhibitor Titers(Baseline, 72 hours postdose, and at 14, 28, 42, 56, 70, and 90 days follow-up)
- Anti-pFVIII Inhibitor Titer(Baseline, 72 hours postdose, and at 14, 28, 42, 56, 70, and 90 days follow-up)
- Terminal Half-life (t1/2) for TAK-672(Pre-dose and at multiple time points post-dose (up to 24 hours) after over 48 hours from the last treatment with TAK-672)
- Clearance (CL) for TAK-672(Pre-dose and at multiple time points post-dose (up to 24 hours) after over 48 hours from the last treatment with TAK-672)
- Volume of Distribution (Vd) for TAK-672(Pre-dose and at multiple time points post-dose (up to 24 hours) after over 48 hours from the last treatment with TAK-672)
- Area Under the Concentration-Time Curve (AUC) for TAK-672(Pre-dose and at multiple time points post-dose (up to 24 hours) after over 48 hours from the last treatment with the initial dose of TAK-672)
- Maximum Drug Concentration (Cmax) Per Dose (Cmax/Dose) for TAK-672(Pre-dose and at multiple time points post-dose (up to 24 hours) after over 48 hours from the last treatment with TAK-672)
- Duration Period From Initial Dose of TAK-672 Until Completion of Hemostasis Control(From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum))
- Total Dose Per Participant From Initial Dose of TAK-672 Until Completion of Hemostasis Control(From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum))
- Number of Participants With New Qualified Severe Bleeding Episodes(From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum))
研究者
研究点 (9)
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