NCT04204408已完成2 期
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Subcutaneous Doses of NNC0365-3769 (Mim8) in Healthy Subjects and in Subjects With Haemophilia A With or Without Factor VIII Inhibitors
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 275
- 试验地点
- 39
- 主要终点
- Part 1: Number of treatment emergent adverse events
研究概览
简要总结
This study is investigating how Mim8 works in people with haemophilia A, who either have inhibitors or do not have inhibitors. Mim8 is a new medication that will be used for prevention of bleeding episodes. Mim8 works by replacing the function of the missing clotting factor VIII (FVIII). Mim8 will be injected with a thin needle in the skin of the stomach, using a pen-injector.
The study will last for up to 44 months. It consists of a main phase (part 1 and part 2) and an extension phase. In part 1, participants will be injected only once with either Mim8 or a "dummy" medicine (placebo) - which one will be decided by chance. In part 2 and the extension phase participants will get an Mim8 injection weekly or monthly.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Sponsor staff involved in the clinical trial is masked according to company standard procedures
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Single ascending dose part 1:
- •Male, aged 18-45 years (both inclusive) at the time of signing informed consent
- •Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator
- •Multiple ascending dose part 2:
- •Male, aged 12-64 years (both inclusive) at the time of signing informed consent (Germany and Japan have local requirements)
- •Diagnosis of congenital haemophilia A with FVIII activity below 1% based on medical records
- •Exploratory biomarker cohort:
- •Male, aged equal to or above 12 years at the time of signing informed consent (Germany and Japan have local requirements)
- •Diagnosis of congenital haemophilia A with FVIII activity below 1% based on medical recordsv
排除标准
- •Factor VIII activity equal to or above 150% at screening
- •Increased risk of thrombosis, e.g. known history of personal or first degree relative(s) with unprovoked deep vein thrombosis
- •Any clinical signs or established diagnosis of venous or arterial thromboembolic disease
- •Known congenital or acquired coagulation disorders other than haemophilia A
- •Increased risk of thrombosis as evaluated by the investigator. E.g. known history of personal or first degree relative(s) with unprovoked deep vein thrombosis with exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing
- •Any clinical signs or established diagnosis of venous or arterial thromboembolic disease with exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing
- •Advanced atherosclerotic disease (e.g. known history of ischemic heart disease, ischemic stroke) as evaluated by the investigator
- •Any autoimmune disease that may increase the risk of thrombosis
- •Receipt of emicizumab or drugs with similar modes of action within 5 half-lives before trial product administration
- •Ongoing or planned immune tolerance induction therapy
- •Exploratory biomarker cohort:
- •Known congenital or acquired coagulation disorders other than haemophilia A
- •Increased risk of thrombosis as evaluated by the investigator. E.g. known history of personal or first degree relative(s) with unprovoked deep vein thrombosis with exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing
- •Any clinical signs or established diagnosis of venous or arterial thromboembolic disease with exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing
- •Advanced atherosclerotic disease (e.g. known history of ischemic heart disease, ischemic stroke) as evaluated by the investigator
- •Any autoimmune disease that may increase the risk of thrombosis
- •Ongoing or planned immune tolerance induction therapy
研究组 & 干预措施
Single dose (part 1) Mim8
Experimental
Blinded. Single doses in healthy volunteers. Dose escalation. In each of the 6 cohorts, 6 participants will receive Mim8.
干预措施: NNC0365-3769 (Mim8) (Drug)
Single dose (part 1) placebo
Placebo Comparator
Blinded. Single doses in healthy volunteers. In each of the 6 cohorts, 2 participants will receive placebo.
干预措施: Placebo (Mim8) (Drug)
Multiple dose (part 2)
Experimental
Open-label. There will be 4 cohorts receiving once-weekly doses (part 2 cohorts 1, 2, 3 and 5) and one cohort receiving once-monthly doses (part 2 cohort 4). Participants will continue into the part 2 extension on the same treatment regimen.
干预措施: NNC0365-3769 (Mim8) (Drug)
结局指标
主要结局
Part 1: Number of treatment emergent adverse events
时间窗: From time of dosing (Day 1) to Week 16
Count
Part 2: Number of treatment emergent adverse events
时间窗: From time of first dosing (Day 1) to Week 12
Count
Part 2, extension: Number of treatment emergent adverse events
时间窗: From Week 12 up to Week 176 (16 weeks after last dose)
Count
次要结局
- Part 2 (weekly and monthly dosing): Relative change in platelets(From baseline (Day 1) to Week 12)
- Part 1: Relative change in platelets(From baseline (Day 1) to Week 16)
- Part 1: Cmax, SD: the maximum concentration of Mim8 after a single dose(From baseline (Day 1) to Week 16)
- Part 1: AUC0-inf, SD: the area under the Mim8 concentration-time curve from time 0 to infinity after a single dose(From baseline (Day 1) to Week 16)
- Part 1: Number of injection site reactions(From time of dosing (Day 1) to Week 16)
- Part 1: Change in activated partial thromboplastin time(From baseline (Day 1) to Week 16)
- Part 2 (weekly and monthly dosing): Number of injection site reactions(From time of first dosing (Day 1) to Week 12)
- Part 2 (weekly and monthly dosing): Relative change in D-dimer(From baseline (Day 1) to Week 12)
- Part 2 (weekly and monthly dosing): Relative change in prothrombin fragment 1 and 2(From baseline (Day 1) to Week 12)
- Part 1: Relative change in prothrombin fragment 1 and 2(From baseline (Day 1) to Week 16)
- Part 1: Relative change in fibrinogen(From baseline (Day 1) to Week 16)
- Part 1: t1/2, SD: the terminal half-life of Mim8 after a single dose(From baseline (Day 1) to Week 16)
- Part 1: Relative change in D-dimer(From baseline (Day 1) to Week 16)
- Part 2 (weekly and monthly dosing): Occurrence of anti-Mim8 antibodies(From baseline (Day 1) to Week 12)
- Part 2 (weekly and monthly dosing): Relative change in fibrinogen(From baseline (Day 1) to Week 12)
- Part 1: tmax, SD: the time to maximum concentration of Mim8 after a single dose(From baseline (Day 1) to Week 16)
- Part 2 PK session 2 (weekly dosing): Cmax, MD: the maximum concentration of Mim8 after multiple doses(From Day 57 to Day 64)
- Part 2 PK session 2 (monthly dosing): AUCτ, MD: the area under the Mim8 concentration-time curve in the dosing interval after multiple doses(From Day 57 to Day 85)
- Part 2 (weekly dosing): Mean of maximum thrombin generation (peak height)(From Day 57 to Day 64)
- Part 2 PK session 2 (weekly dosing): AUCτ, MD: the area under the Mim8 concentration-time curve in the dosing interval after multiple doses(From Day 57 to Day 64)
- Part 2 PK session 2 (monthly dosing): Cmax, MD: the maximum concentration of Mim8 after multiple doses(From Day 57 to Day 85)
- Part 2 (monthly dosing): Mean of maximum thrombin generation (peak height)(From Day 57 to Day 85)
- Part 2, extension: Number of injection site reactions(From Week 12 up to Week 176 (16 weeks after last dose))
- Part 2, extension: Occurrence of anti-Mim8 antibodies(From Week 12 up to Week 176 (16 weeks after last dose))
研究者
研究点 (39)
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