Efficacy and Safety of Concizumab Prophylaxis in Patients With Haemophilia A or B With Inhibitors
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 134
- 试验地点
- 178
- 主要终点
- Rate of Treated Spontaneous and Traumatic Bleeding Episodes
研究概览
简要总结
This study will test how well a new medicine called concizumab works in the body of people with haemophilia A or B with inhibitors. The purpose is to show that concizumab can prevent bleeds in the body and is safe to use. Participants who usually only take medicine to treat bleeds (on-demand) will be placed in one of two groups. In one group, participants will get study medicine from the start of the study. In the other group, participants will continue with their normal medicine and get study medicine after 6 months. Which treatment the participant gets is decided by chance. Participants who usually take medicine to prevent bleeds (prophylaxis treatment) or who are already being treated with concizumab (study medicine) will receive the study medicine from the start of the study. Participants will get 1 injection with the study medicine every day under the skin. This participants will have to do themselves and can be done at home. The study doctor will hand out the medicine in the form of a pen-injector. The pen-injector will contain the study medicine. The study will last for about seven years. The length of time the participants will be in the study depends on when they agreed to take part or when the medicine is available for purchase in their country (31 December 2026 at the latest). The time between visits will be approximately 4 weeks for the first 6 to 12 months, depending on the group participants are in and approximately 8 weeks for the rest of the study. Participants will be asked to record information into an electronic diary during the study and may also be asked to wear an activity tracker.
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
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
- •Male aged 12 years or older at the time of signing informed consent.
- •Congenital Haemophilia A or B of any severity with documented history of inhibitor (equal to or above 0.6 Bethesda Units (BU).
- •Patient has been prescribed, or in need of, treatment with bypassing agents in the last 24 weeks prior to screening (for patients not previously enrolled in NN7415-4310 (explorer 4)).
排除标准
- •Known or suspected hypersensitivity to any constituent of the trial product or related products.
- •Known inherited or acquired coagulation disorder other than congenital haemophilia.
- •Ongoing or planned Immune Tolerance Induction treatment.
- •History of thromboembolic disease (includes arterial and venous thrombosis including myocardial infarction, pulmonary embolism, cerebral infarction/thrombosis, deep vein thrombosis, other clinically significant thromboembolic events and peripheral artery occlusion). Current clinical signs of, or treatment for thromboembolic disease. Patients who in the judgement of the investigator are considered at high risk of thromboembolic events (thromboembolic risk factors could include, but are not limited to, hypercholesterolemia, diabetes mellitus, hypertension, obesity, smoking, family history of thromboembolic events, arteriosclerosis, other conditions associated with increased risk of thromboembolic events.)
研究组 & 干预措施
Arm 1: No prophylaxis
Haemophilia A with inhibitors (HAwI) and haemophilia B with inhibitors (HBwI) patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis. In the extension part, patients in arm 1 will receive daily concizumab subcutaneous (s.c., under the skin) injections.
干预措施: Concizumab (Drug)
Arm 4: Concizumab prophylaxis
Patients previously on prophylaxis with by-passing agents and on-demand patients who are screened at a timepoint where the required number of patients in arms 1 and 2 have been randomised. These patients will, if eligible, be enrolled into the trial and will initiate concizumab prophylaxis at visit 2a (week 0).
干预措施: Concizumab (Drug)
Arm 2: Concizumab prophylaxis
HAwI and HBwI patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis.
干预措施: Concizumab (Drug)
Arm 3: Concizumab prophylaxis
The HAwI and HBwI patients enrolled into the concizumab phase 2 trial (NN7415-4310) at time of transfer will be offered enrolment into this trial. It is required that these patients are on concizumab prophylaxis up until enrolment into the trial. These patients will continue concizumab prophylaxis.
干预措施: Concizumab (Drug)
结局指标
主要结局
Rate of Treated Spontaneous and Traumatic Bleeding Episodes
时间窗: On demand (arm 1): From week 0 up until start of concizumab treatment (at least 24 weeks) Concizumab (arm 2): From week 0 up until the primary analysis cut-off (at least 32 weeks)
Rate of treated spontaneous and traumatic bleeding episodes is presented. The observation period used for reporting this endpoint is on-treatment without ancillary therapy excl. data on initial regimen for participants exposed to both regimens (OTwoATexIR). It is defined as the time period where participants are treated by either the new concizumab dosing regimen or the initial concizumab dosing regimen (only included if not exposed to the new concizumab dosing regimen) or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleed during any of the cases. The data is reported in the terms of annualised bleeding rate (ABR). Week 0 is defined as time of randomisation to on-demand administration or time of start of the new concizumab dosing regimen.
次要结局
- Rate of Treated Spontaneous Bleeding Episodes(On demand (arm 1): From week 0 up until start of concizumab treatment (at least 24 weeks) Extension concizumab (arm 1): From start of new concizumab dosing regimen (week 25) up until week 56 cut-off Concizumab (arm 2): From week 0 up until week 56 cut-off)
- Rate of Treated Spontaneous and Traumatic Joint Bleeds(On demand (arm 1): From week 0 up until start of concizumab treatment (at least 24 weeks) Extension concizumab (arm 1): From start of new concizumab dosing regimen (week 25) up until week 56 cut-off Concizumab (arm 2): From week 0 up until week 56 cut-off)
- Rate of Treated Spontaneous and Traumatic Target Joint Bleeds(On demand (arm 1): From week 0 up until start of concizumab treatment (at least 24 weeks) Extension concizumab (arm 1): From start of new concizumab dosing regimen (week 25) up until week 56 cut-off Concizumab (arm 2): From week 0 up until week 56 cut-off)
- Change in 36-item Short Form Health Survey (SF-36v2) Bodily Pain(Baseline (week 0), Week 24)
- Change in SF36v2 Physical Functioning(Baseline (week 0), Week 24)
- Number of Thromboembolic Events(From week 0 to end of trial (week 167))
- Number of Hypersensitivity Type Reactions(From week 0 to end of trial (week 167))
- Number of Injection Site Reactions(From week 0 to end of trial (week 167))
- Number of Participants With Antibodies to Concizumab(From week 0 to end of trial (week 167))
- Pre-dose (Trough) Concizumab Plasma Concentration (Ctrough)(Pre-dose (prior to concizumab administration at week 56))
- Pre-dose Thrombin Peak(Pre-dose (prior to concizumab administration at week 56))
- Pre-dose Free Tissue Factor Pathway Inhibitor (TFPI) Concentration(Pre-dose (prior to concizumab administration at week 56))
- Maximum Concizumab Plasma Concentration (Cmax)(Week 24: Predose, 3 hours (h), 6h, 9h, 24h)
- Area Under the Concizumab Plasma Concentration-time Curve (AUC)(Week 24: Predose, 3 hours (h), 6h, 9h, 24h)
- Number of Injection Site Reactions(On demand (arm 1 ): From week 0 until start of concizumab treatment (atleast 24 weeks) Concizumab (arms 2-4): From week 0 up until week 56 cut-off Extension Concizumab (arm 1): From start of new concizumab dosing regimen (week 25) up until week 56 cut-off)
- Number of Participants With Antibodies to Concizumab(Concizumab (arms 2-4): From week 0 up until week 56 cut-off Extension Concizumab (arm 1): From start of new concizumab dosing regimen (week 25) up until week 56 cut-off)
- Number of Thromboembolic Events(On demand (arm 1 ): From week 0 until start of concizumab treatment (atleast 24 weeks) Concizumab (arms 2-4): From week 0 up until week 56 cut-off Extension Concizumab (arm 1): From start of new concizumab dosing regimen (week 25) up until week 56 cut-off)
- Number of Hypersensitivity Type Reactions(On demand (arm 1 ): From week 0 until start of concizumab treatment (atleast 24 weeks) Concizumab (arms 2-4): From week 0 up until week 56 cut-off Extension Concizumab (arm 1): From start of new concizumab dosing regimen (week 25) up until week 56 cut-off)