NCT03103542已完成4 期
A Non-Controlled, Open-Label, Multicenter, Study of Immune Tolerance Induction Performed With rFVIIIFc Within a Timeframe of 60 Weeks in Severe Haemophilia A Patients With Inhibitors Who Have Failed Previous Immune Tolerance Induction Therapies
Swedish Orphan Biovitrum2 个研究点 分布在 2 个国家目标入组 16 人开始时间: 2017年8月29日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- ITI Success
研究概览
简要总结
The primary purpose of this study is to describe the outcome of Immune Tolerance Induction (ITI) treatment performed with rFVIIIFc within a timeframe of 60 weeks in patients with haemophilia A who have failed previous attempts at tolerization.
详细描述
This is an open-label, single-arm, interventional multi-center study designed to explore ITI performed with recombinant coagulation factor VIII Fc fusion protein (rFVIIIFc) within a timeframe of 60 weeks in patients with severe haemophilia A, who have failed previous attempts at tolerization including use of immunosuppressants.
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
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Signed and dated informed consent provided by the patient, or the patient's legally authorized representative for patients under the legal age. Assent should be obtained from pediatric patients according to local regulations
- •Male patients of any age diagnosed with severe haemophilia A, as confirmed from the medical record
- •Previously treated with any plasma-derived or recombinant conventional or extended half-life FVIII
- •Diagnosed with high titer inhibitors (historical peak ≥5 Bethesda units (BU)/mL according to medical records)
- •Inhibitor titer >0.6 BU at screening
- •Failed previous ITI attempt(s) with any plasma-derived or recombinant conventional or extended half-life FVIII including the use of immunosuppressant The attempt should be documented in the medical records and have the following characteristics:
- •A minimum FVIII dose equivalent to the low dose arm of the International ITI study (50 IU/kg, 3 times/week)
- •A minimum ITI treatment period of 33 months or
- •Shorter than 33 months if no downward trend of at least 20% in the inhibitor titer in a 6-month period after the initial 3 months of the ITI treatment
- •All patients must practice effective contraception during the study and for 3 months after their last dose of study treatment
排除标准
- •Other coagulation disorder(s) in addition to haemophilia A
- •History of hypersensitivity reactions associated with any rFVIIIFc administration
- •High risk of cardiovascular, cerebrovascular, or other thromboembolic events, as judged by the investigator
- •Planned major surgery to be deferred after study completion. Minor surgery such as tooth extraction or insertion/replacement of central venous access device is allowed.
- •Concurrent systemic treatment with immunosuppressive drugs within 12 weeks prior to screening. Exceptions to this include: ribavirin for treatment of Hepatitis C virus (HCV), and/or systemic steroids (a total of 2 courses of pulse treatments lasting no more than 7 days within 12 weeks prior to Day 1) and/or inhaled steroids
- •Abnormal renal function (serum creatinine >2.0 mg/dL) as assessed by local lab
- •Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 × upper limit of normal (ULN) as assessed by local lab
- •Serum total bilirubin >3 × ULN as assessed by local lab
- •Cluster of differentiation 4 (CD4) lymphocytes ≤200 mm3 if known as HIV antibody positive at Screening
- •Viral load of ≥400 copies/mL if known HIV antibody positive at Screening
- •Patients with a documented history of alcohol or substance abuse within 12 months prior to randomization
- •Previous inclusion in this study
- •Participation in another concurrent clinical interventional study within 30 days of screening or intake of an investigational drug within five half-lives of that investigational drug has passed
- •Foreseeable inability to cooperate with given instructions or study procedures
- •Presence of any medical or psychological condition or laboratory result that in the opinion of the investigator can interfere with the patient's ability to comply with the protocol requirements or makes the patient not appropriate for inclusion to the study and treatment with rFVIIIFc
研究组 & 干预措施
Recombinant coagulation factor VIII Fc (rFVIIIFc)
Experimental
Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc.
干预措施: Recombinant coagulation factor (rFVIIIFc) (Biological)
结局指标
主要结局
ITI Success
时间窗: up to 60 weeks
Number of patients who achieve ITI success where ITI success is defined as achieving all 3 of the following criteria: * Negative titer for inhibitor (\<0.6 Bethesda units/mL by the Nijmegen-modified Bethesda assay) at 2 consecutive visits * FVIII incremental recovery (IR) \>66% of the expected IR at 2 consecutive visits * FVIII half-life (t½) ≥7 hours
次要结局
- Time to ITI Success(up to 60 weeks)
- Occurrence of Relapse During a 48-week Period Following Successful ITI Treatment(Up to 48 weeks)
- Number of Bleedings During ITI Treatment(up to 60 weeks)
- Bleeding Rate During a 48-week Period Following Successful ITI Treatment(up to 48 weeks)
- Adverse Events (AEs)(SAEs - approx 166 weeks AEs - approx 110 weeks)
- Consumption of rFVIIIFc(Up to 60 weeks)
- Number of Days Missed School or Work During ITI Treatment(up to 60 weeks)
- Number of Days Missed School or Work During a 48-week Period Following Successful ITI Treatment(up to 48 weeks)
- Number of Hospitalizations During ITI Treatment(up to 60 weeks)
- Number of Hospitalizations During a 48-week Period Following Successful ITI Treatment(Up to 48 weeks)
- Adherence(up to 108 weeks)
研究者
研究点 (2)
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