Prospective, Single-Arm, Open-Label Use of Hemlibra (Emicizumab) in the Treatment of Mild Hemophilia A
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Interaction of Hemlibra (emicizumab) binding with endogenous altered FVIII protein in an individual with mild hemophilia A and the combined effect on thrombin generation and hemostatic characteristics
研究概览
简要总结
This is a single arm, phase 4, prospective, open-label, United States single-center study to determine the hemostatic characteristics of Hemlibra (emicizumab) as measured by coagulation laboratory parameters in the mild hemophilia A male patient population with endogenous altered FVIII (baseline FVIII activity of >5% to 30%). The safety and hemostatic efficacy of Hemlibra (emicizumab) in this patient population will be investigated. Secondary outcomes will assess changes in joint health and quality of life in treated patients.
详细描述
This is a single arm, phase 4, prospective, open-label, United States single-center study to develop laboratory data and assess the clinical hemostatic efficacy and safety of Hemlibra (emicizumab) for hemostatic control of mild hemophilia A patients (baseline FVIII activity, >5 to 30%). Males aged ≥5 years to ≤45 years without inhibitors are eligible for enrollment. Secondary outcomes will assess changes in quality of life and joint health in treated patients.
Approximately 20 patients will be enrolled. As much as possible, the patient population will be selected to provide a variety of FVIII activity levels and F8 genetic defects.
Carrier females are not eligible for the study as the goal is to examine the effect of altered FVIII on Hemlibra (emicizumab) binding; carrier females with FVIII levels in the mild range of deficiency have one altered and one normal F8 gene that results in a mixture of both normal and altered FVIII proteins thereby complicating the interpretation of study results.
Patients with a FVIII inhibitor (or a history of a FVIII inhibitor) are not eligible for this study; if a subject develops a FVIII inhibitor during the study, they will be withdrawn from the study and offered the current standard of care.
Patients <5 years of age will be excluded from the study due to 1) the number of blood draws and the quantity of blood required; and 2) likelihood of reaching a minimum weight to utilize Stimate (~20 kg).
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
- 5 Years 至 45 Years（Child, Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent form from the subject, parent or guardian
- •Diagnosis of mild congenital hemophilia A (baseline FVIII level of >5% to 30%) without a current FVIII inhibitor or a history of FVIII inhibitor
- •Any number of FVIII exposure days, including PUPs
- •Age ≥5 years to ≤45 years
- •Medical documentation of bleeding events, outcomes and hemostatic product usage for 12 months prior to study enrollment
- •Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the health-related questionnaires, activity tracking, and bleed diaries, using systems provided during the study
- •Willingness to undergo a Stimate/DDAVP challenge (only if the subject reports no adverse event associated with prior Stimate [DDAVP/desmopressin acetate] use); Stimate/DDAVP challenge will not be performed if the patient has a documented history of lack of response as defined by an increase of FVIII < 2 times baseline level
- •Adequate hepatic function, defined as total bilirubin ≤1.5 × age-adapted upper limit of normal (ULN) (excluding Gilbert's syndrome) and both AST and ALT ≤3 × age-adapted ULN at the time of screening, and no clinical signs or known laboratory/radiographic evidence consistent with cirrhosis
- •Adequate hematologic function, defined as a platelet count ≥100,000/μL and a PT≤1.5 times the ULN at the time of screening
- •Adequate renal function, defined as serum creatinine ≤2.5 × age-adapted ULN and creatinine clearance ≥30 mL/min by Cockcroft-Gault formula
排除标准
- •Inherited or acquired bleeding disorder other than mild congenital hemophilia A (baseline FVIII level of >5% to 30%)
- •Any bleeding disorder other than or in addition to mild hemophilia A
- •Current or prior inhibitor to FVIII (any titer)
- •Female sex
- •History of CVD, risk of CVD by the ASCVD risk estimator (defined as a subject having >20% risk of a cardiovascular event within the next 10 years if the subject is ≥20 years of age) and/or a history of ischemic heart disease [ICD codes 120-125]
- •High risk for TMA (eg, have a previous medical or family history of TMA), in the Study Investigator's judgment
- •History of illicit drug or alcohol abuse by report or in the Study Investigator's judgment
- •Previous (within the last 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or signs of thromboembolic disease
- •Other conditions (eg, certain autoimmune diseases) that may currently increase the risk of bleeding or thrombosis
- •History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the Hemlibra (emicizumab) injection
- •Known HIV infection with CD4 counts <200 cells/μL. HIV infection with CD4 counts ≥200 cells/μL permitted
- •Use of systemic immunomodulators (eg, interferon) at enrollment or planned use during the study, with the exception of anti-retroviral therapy
- •Concomitant disease, condition, significant abnormality on screening evaluations or laboratory tests, or treatment that could interfere with the conduct of the study, or that would, in the opinion of the Study Investigator, pose an additional unacceptable risk in administering study drug to the patient
- •Receipt of any of the following:
- •Hemlibra (emicizumab) in a prior investigational study
- •An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration
- •A non-hemophilia-related investigational drug within last 30 days or 5 half-lives, whichever is shorter
- •Any other investigational drug currently being administered or planned to be administered
- •Inability to comply with the study protocol in the opinion of the Study Investigator
研究组 & 干预措施
Single Arm
Patients with mild hemophilia A (without inhibitors) will be treated with prophylactic emicizumab. The clinical hemostatic efficacy and safety will be assessed. Secondary outcomes will assess changes in quality of life and joint health in treated patients.
干预措施: Emicizumab (Drug)
结局指标
主要结局
Interaction of Hemlibra (emicizumab) binding with endogenous altered FVIII protein in an individual with mild hemophilia A and the combined effect on thrombin generation and hemostatic characteristics
时间窗: Before treatment, month 4, month 7, and month 13
Change in FVIII human chromogenic activity, FVIII bovine chromogenic activity, and Thrombin Generation Assay relatively to one another
次要结局
- Alternate hemostatic therapies with surgery(At time of patient's surgery if applicable)
- AE, SAE, and ADA(Through study completion annually, up to 35 months)
- Breakthrough bleeds(Through study completion, up to 35 months)
- Factor VIII alteration and coagulation(Before treatment, month 4, month 7, and month 13)
- ADA development(ADA assay at month 4, month 7, month 13, and end of study participation)
- Change from baseline joint disease annually(Through study completion annually, up to 35 months)
- Change in quality of life: questionnaire(Before treatment, Day 0, Day 7, Day 14, Day 21, month 13, month 25)
- Change in activity: questionnaire(Before treatment, Day 0, Day 7, Day 14, Day 21, month 13, month 25)
研究者
Amy D Shapiro, MD
Medical Director
Indiana Hemophilia &Thrombosis Center, Inc.