NCT06998524招募中3 期
A Phase III, Multicenter, Open-Label Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Emicizumab Prophylaxis in Patients With Type 3 Von Willebrand Disease
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 75
- 试验地点
- 48
- 主要终点
- Annualized Bleed Rate (ABR) for Treated Bleeds in the Randomized Arms
研究概览
简要总结
This is a Phase III, multicenter, open-label clinical study designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab prophylaxis in participants aged 1 month and above, who have been diagnosed with Type 3 von Willebrand disease (VWD). Participants on prior standard of care (SOC) on-demand therapy will be assessed via a randomized comparison (Arm A - emicizumab prophylaxis and Arm B - continuation of SOC on-demand therapy), while participants on prior SOC prophylactic therapy (Arm C - emicizumab prophylaxis) will be assessed via intra-participant analysis with data obtained from the preceding non-interventional study (NIS), WP45335 (NCT06883240).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Month 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of Type 3 von Willebrand disease (VWD), based on medical records
- •Preexisting medical record verifying the status of von Willebrand factor (VWF) inhibitor (positive or negative, including titer if available)
- •Adequate hematologic, hepatic, and renal function
- •For participants of childbearing potential: agreement to remain abstinent or adhere to the contraception requirements
- •Additional Inclusion Criteria for Arms A and B:
- •Age ≥1 month at the time of signing Informed Consent/Assent Form
- •Documented previous use of on-demand therapy with intermittent (less than once a week) on-demand SOC therapy for VWD
- •Having ≥2 treated bleeds (except menstrual bleeds) with factor concentrate within 24 weeks prior to enrollment
- •Additional Inclusion Criteria for Arm C:
- •Age ≥2 years at the time of signing Informed Consent/Assent Form
- •Documented and confirmed previous use of SOC prophylactic therapy for VWD (1-3 times weekly, as per prescribed dose) as described in the eligibility of Study WP45335
- •Have completed all study requirements as defined in the WP45335 protocol for at least 24 weeks
排除标准
- •Inherited or acquired bleeding disorder other than Congenital Type 3 VWD
- •History of gastrointestinal bleeding within 18 months prior to enrollment, or any previous diagnosis of angiodysplasia
- •History of intracranial hemorrhage
- •Previous or current treatment for thromboembolic disease or signs of thromboembolic disease
- •Other conditions (e.g., certain autoimmune diseases) that may increase risk of bleeding or thrombosis
- •History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
- •Use of systemic immunomodulators (e.g., interferon) at enrollment or planned use during the study, with the exception of anti-retroviral therapy
研究组 & 干预措施
Treatment Extension Period for All Arms: Emicizumab Prophylaxis
Experimental
Participants in Arms A and C who have completed 24 weeks of emicizumab prophylaxis and who derive benefit from emicizumab will have the opportunity to continue to receive emicizumab prophylaxis in the extension period. Participants in Arm B who have completed 24 weeks of SOC on-demand treatment will have the opportunity to receive emicizumab prophylaxis in the extension period.
干预措施: Emicizumab (Drug)
Arm B (Prior On-Demand SOC): On-Demand SOC for 24 Weeks
Active Comparator
Participants who are randomized to Arm B, taking on-demand standard of care (SOC) treatment at the time of study entry (and for at least 24 weeks prior to enrollment), will continue to receive their current SOC on-demand treatment until Week 24.
干预措施: Factor VIII (FVIII) Concentrates (Drug)
Arm B (Prior On-Demand SOC): On-Demand SOC for 24 Weeks
Active Comparator
Participants who are randomized to Arm B, taking on-demand standard of care (SOC) treatment at the time of study entry (and for at least 24 weeks prior to enrollment), will continue to receive their current SOC on-demand treatment until Week 24.
干预措施: von Willebrand Factor (VWF) Concentrates (Drug)
Arm A (Prior On-Demand SOC): Emicizumab Prophylaxis for 24 Weeks
Experimental
Participants who are randomized to Arm A, taking on-demand standard of care (SOC) treatment at the time of study entry (and for at least 24 weeks prior to enrollment), will receive emicizumab SC prophylaxis.
干预措施: Emicizumab (Drug)
Arm B (Prior On-Demand SOC): On-Demand SOC for 24 Weeks
Active Comparator
Participants who are randomized to Arm B, taking on-demand standard of care (SOC) treatment at the time of study entry (and for at least 24 weeks prior to enrollment), will continue to receive their current SOC on-demand treatment until Week 24.
干预措施: Bypassing Agents (Drug)
Arm B (Prior On-Demand SOC): On-Demand SOC for 24 Weeks
Active Comparator
Participants who are randomized to Arm B, taking on-demand standard of care (SOC) treatment at the time of study entry (and for at least 24 weeks prior to enrollment), will continue to receive their current SOC on-demand treatment until Week 24.
干预措施: von Willebrand Factor (VWF) and Factor VIII (FVIII) Concentrates (Drug)
Arm C (Prior Prophylaxis SOC): Emicizumab Prophylaxis for 24 Weeks
Experimental
Participants who enroll in Arm C, taking SOC prophylactic treatment at the time of study entry and for at least 24 weeks of observation during the preceding NIS WP45335, will receive emicizumab SC prophylaxis.
干预措施: Emicizumab (Drug)
结局指标
主要结局
Annualized Bleed Rate (ABR) for Treated Bleeds in the Randomized Arms
时间窗: From Baseline to at least 24 weeks
次要结局
- ABR for All Bleeds in the Randomized Arms(From Baseline to at least 24 weeks)
- ABR for Treated Spontaneous Bleeds in the Randomized Arms(From Baseline to at least 24 weeks)
- ABR for Treated Joint Bleeds in the Randomized Arms(From Baseline to at least 24 weeks)
- Intra-Participant Comparison of the ABR for Treated Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding Non-Interventional Study (NIS) WP45335(From Baseline to at least 24 weeks)
- Intra-Participant Comparison of the ABR for All Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding NIS WP45335(From Baseline to at least 24 weeks)
- Intra-Participant Comparison of the ABR for Treated Spontaneous Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding NIS WP45335(From Baseline to at least 24 weeks)
- Intra-Participant Comparison of the ABR for Treated Joint Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding NIS WP45335(From Baseline to at least 24 weeks)
- Incidence and Severity of Adverse Events, with Severity Determined According to the World Health Organization (WHO) Toxicity Grading Scale(From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months))
- Incidence and Severity of Thromboembolic Events(From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months))
- Incidence and Severity of Thrombotic Microangiopathy Events(From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months))
- Incidence and Severity of Injection-Site Reactions(From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months))
- Incidence of Adverse Events Leading to Drug Discontinuation(From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months))
- Incidence of Severe Hypersensitivity, Anaphylaxis, or Anaphylactoid Reactions(From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months))
- Incidence of Clinical Laboratory Abnormalities(From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months))
- Trough Plasma Concentration of Emicizumab at Prespecified Timepoints During the Treatment Period(Predose and at prespecified timepoints from first dose of emicizumab until study completion (up to 3 years, 11 months))
- Percentage of Participants with Anti-Drug Antibodies (ADAs) to Emicizumab at Baseline and with ADAs to Emicizumab During the Treatment Period(Baseline and at prespecified timepoints from first dose of emicizumab until study completion (up to 3 years, 11 months))
- Change from Baseline in Respiratory Rate Over Time(Baseline, Weeks 1, 2, 25, and every 12 weeks thereafter (weeks after switch to emicizumab for Arm B only) until study completion (up to 3 years, 11 months))
- Change from Baseline in Pulse Rate Over Time(Baseline, Weeks 1, 2, 25, and every 12 weeks thereafter (weeks after switch to emicizumab for Arm B only) until study completion (up to 3 years, 11 months))
- Change from Baseline in Systolic Blood Pressure Over Time(Baseline, Weeks 1, 2, 25, and every 12 weeks thereafter (weeks after switch to emicizumab for Arm B only) until study completion (up to 3 years, 11 months))
- Change from Baseline in Diastolic Blood Pressure Over Time(Baseline, Weeks 1, 2, 25, and every 12 weeks thereafter (weeks after switch to emicizumab for Arm B only) until study completion (up to 3 years, 11 months))
- Change from Baseline in Body Temperature Over Time(Baseline, Weeks 1, 2, 25, and every 12 weeks thereafter (weeks after switch to emicizumab for Arm B only) until study completion (up to 3 years, 11 months))
- Change from Baseline in Electrocardiogram (ECG) Parameters Over Time: QT, QTcF, RR, PR, and QRS Intervals(Baseline and study completion (up to 3 years, 11 months))
- Change from Baseline in Heart Rate Over Time, as Measured by Electrocardiogram (ECG)(Baseline and study completion (up to 3 years, 11 months))
- Percentage of Participants with Anti-Drug Antibodies (ADAs) to Emicizumab at Baseline and with ADAs to Emicizumab During the Treatment Period(Baseline and at prespecified timepoints from first dose of emicizumab until study completion (up to 3 years, 11 months))
- Change from Baseline in Systolic Blood Pressure Over Time(Baseline, Weeks 1, 2, 25, and every 12 weeks thereafter (weeks after switch to emicizumab for Arm B only) until study completion (up to 3 years, 11 months))
- Change from Baseline in Diastolic Blood Pressure Over Time(Baseline, Weeks 1, 2, 25, and every 12 weeks thereafter (weeks after switch to emicizumab for Arm B only) until study completion (up to 3 years, 11 months))
- Change from Baseline in Respiratory Rate Over Time(Baseline, Weeks 1, 2, 25, and every 12 weeks thereafter (weeks after switch to emicizumab for Arm B only) until study completion (up to 3 years, 11 months))
- ABR for All Bleeds in the Randomized Arms(From Baseline to at least 24 weeks)
- ABR for Treated Spontaneous Bleeds in the Randomized Arms(From Baseline to at least 24 weeks)
- ABR for Treated Joint Bleeds in the Randomized Arms(From Baseline to at least 24 weeks)
- Intra-Participant Comparison of the ABR for Treated Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding Non-Interventional Study (NIS) WP45335(From Baseline to at least 24 weeks)
- Intra-Participant Comparison of the ABR for All Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding NIS WP45335(From Baseline to at least 24 weeks)
- Intra-Participant Comparison of the ABR for Treated Spontaneous Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding NIS WP45335(From Baseline to at least 24 weeks)
- Intra-Participant Comparison of the ABR for Treated Joint Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding NIS WP45335(From Baseline to at least 24 weeks)
- Incidence and Severity of Adverse Events, with Severity Determined According to the World Health Organization (WHO) Toxicity Grading Scale(From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months))
- Incidence and Severity of Thromboembolic Events(From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months))
- Incidence and Severity of Thrombotic Microangiopathy Events(From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months))
- Incidence and Severity of Injection-Site Reactions(From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months))
- Incidence of Adverse Events Leading to Drug Discontinuation(From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months))
- Incidence of Severe Hypersensitivity, Anaphylaxis, or Anaphylactoid Reactions(From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months))
- Incidence of Clinical Laboratory Abnormalities(From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months))
- Trough Plasma Concentration of Emicizumab at Prespecified Timepoints During the Treatment Period(Predose and at prespecified timepoints from first dose of emicizumab until study completion (up to 3 years, 11 months))
- Change from Baseline in Pulse Rate Over Time(Baseline, Weeks 1, 2, 25, and every 12 weeks thereafter (weeks after switch to emicizumab for Arm B only) until study completion (up to 3 years, 11 months))
- Change from Baseline in Body Temperature Over Time(Baseline, Weeks 1, 2, 25, and every 12 weeks thereafter (weeks after switch to emicizumab for Arm B only) until study completion (up to 3 years, 11 months))
- Change from Baseline in Electrocardiogram (ECG) Parameters Over Time: QT, QTcF, RR, PR, and QRS Intervals(Baseline and study completion (up to 3 years, 11 months))
- Change from Baseline in Heart Rate Over Time, as Measured by Electrocardiogram (ECG)(Baseline and study completion (up to 3 years, 11 months))
- Change from Baseline in the PROMIS-29 Questionnaire Pain Interference Domain Score Over Time(Baseline and at prespecified timepoints until study completion (up to 3 years, 11 months))
- Change from Baseline in the PROMIS-29 Questionnaire Fatigue Domain Score Over Time(Baseline and at prespecified timepoints until study completion (up to 3 years, 11 months))
研究者
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