Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous, Oral and Subcutaneous Doses of Inno8 in Healthy Male Participants
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 108
- 试验地点
- 2
- 主要终点
- SAD: Number of treatment emergent adverse events
研究概览
简要总结
This study will test how different doses of study medicine (Inno8) work in the healthy men. The purpose of this study is to prove safety of Inno8 in healthy men, which will support further development of Inno8 in people with Haemophilia A. The study consists of three parts: single ascending dose (SAD), multiple ascending dose (MAD) and single subcutaneous dose (SSD). Each part will have more than one cohort (like sub-parts). No matter which part the participants will be enrolled in, they will either get the study medicine (Inno8) or a dummy medicine that looks like the study medicine but has no effect on the body (placebo). Which treatment participants get is decided by chance. The study medicine is a new medicine that cannot be prescribed by doctors. In the SAD and SSD part participants will receive a single injection of study medicine or placebo, and the study will last for up to 9 weeks. In the MAD part, participants will receive 1-2 tablets of study medicine or placebo daily for 10 days, and the study will last for up to 11 weeks.
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
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Age 18-45 years (both inclusive) at the time of signing informed consent
- •Body mass index between 18.5 and 29.9 Kilogram Per Square Meter (kg/m^2) (both inclusive)
- •Body weight between 60.0 and 100.0 Kilogram (kg) (both inclusive)
- •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
排除标准
- •Factor VIII activity greater than or equal to (≥) 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
- •Any of the thrombophilia markers listed below:
- •Protein C, protein S or antithrombin below the lower normal laboratory range
- •Factor II activity, activated protein C resistance, lupus anticoagulant, anti-cardiolipin antibody (IgG and IgM) or anti-β2 glycoprotein I antibody (IgG and IgM) outside the normal laboratory range at screening
研究组 & 干预措施
Cohort 1 (SAD): NNC0442-0344 A
Participants will receive single dose of NNC0442-0344 A intravenously.
干预措施: NNC0442-0344 A (Drug)
Cohort 2 (SAD): NNC0442-0344 A
Participants will receive single dose of NNC0442-0344 A intravenously.
干预措施: NNC0442-0344 A (Drug)
Cohort 3 (SAD): NNC0442-0344 A
Participants will receive single dose of NNC0442-0344 A intravenously.
干预措施: NNC0442-0344 A (Drug)
Cohort 4 (SAD): NNC0442-0344 A
Participants will receive single dose of NNC0442-0344 A intravenously.
干预措施: NNC0442-0344 A (Drug)
Cohort 5 (SAD): NNC0442-0344 A
Participants will receive single dose of NNC0442-0344 A intravenously.
干预措施: NNC0442-0344 A (Drug)
Cohort 1 (MAD): NNC0442-0344 A
Participants will receive a oral daily dose of NNC0442-0344 A for 10 days.
干预措施: NNC0442-0344 A (Drug)
Cohort 2 (MAD): NNC0442-0344 A
Participants will receive a oral daily dose of NNC0442-0344 A for 10 days.
干预措施: NNC0442-0344 A (Drug)
Cohort 3 (MAD): NNC0442-0344 A
Participants will receive a oral daily dose of NNC0442-0344 A for 10 days.
干预措施: NNC0442-0344 A (Drug)
Cohort 4 (MAD): NNC0442-0344 A
Participants will receive a oral daily dose of NNC0442-0344 A for 10 days.
干预措施: NNC0442-0344 A (Drug)
Cohort 1 (SSD): NNC0442-0344 A
Participants will receive single dose of NNC0442-0344 A subcutaneously.
干预措施: NNC0442-0344 A (Drug)
Cohort 2 (SSD): NNC0442-0344 A
Participants will receive single dose of NNC0442-0344 A subcutaneously.
干预措施: NNC0442-0344 A (Drug)
SAD: Placebo
Participants will receive single dose of placebo intravenously.
干预措施: Placebo (Drug)
MAD: Placebo
Participants will receive a oral daily dose of Placebo for 10 days.
干预措施: Placebo (Drug)
SSD: Placebo
Participants will receive single dose of placebo subcutaneously.
干预措施: Placebo (Drug)
结局指标
主要结局
SAD: Number of treatment emergent adverse events
时间窗: From time of dosing (Day 1) to Day 36
Measured as count of events.
MAD: Number of treatment emergent adverse events
时间窗: From time of dosing (Day 1) to end of follow-up (Day 46)
Measured as count of events.
SSD: Number of treatment emergent adverse events
时间窗: From time of dosing (Day 1) to Day 36
Measured as count of events.
次要结局
- SAD: T1/2, SD: the terminal half-life of Inno8 after a single dose(From baseline (Day 1) to Day 36)
- SAD: Change in D-dimer(From baseline (Day 1) to Day 36)
- SAD: Change in prothrombin fragment 1 and 2(From baseline (Day 1) to Day 36)
- SAD: Cmax, SD: the maximal concentration of Inno8 after a single dose(From baseline (Day 1) to Day 36)
- SAD: AUC, SD: the area under the concentration curve of Inno8 after a single dose(From baseline (Day 1) to Day 36)
- SAD: Maximum change in activated partial thromboplastin time(From baseline (Day 1) to Day 36)
- SAD: Maximum thrombin generation (peak height)(From baseline (Day 1) to Day 36)
- MAD: Change in D-dimer(From baseline (Day 1) to Day 46)
- MAD: Change in prothrombin fragment 1 and 2(From baseline (Day 1) to Day 46)
- MAD: Change in platelets(From baseline (Day 1) to Day 46)
- SAD: Change in fibrinogen(From baseline (Day 1) to Day 36)
- SAD: Change in platelets(From baseline (Day 1) to Day 36)
- MAD: Change in fibrinogen(From baseline (Day 1) to Day 46)
- MAD: Occurrence of anti-Inno8 antibodies(From baseline (Day 1) to Day 46)
- MAD: Cmax: The maximum concentration of Inno8 after multiple doses(From Day 10 to Day 11)
- MAD: Tmax: The time to Cmax after last multiple dose(From Day 10 to Day 11)
- MAD: Tmax: The time to Cmax after first dose(From Day 1 to Day 2)
- MAD: AUC: the area under the Inno8 concentration-time curve in the dosing interval after multiple doses(From Day 10 to Day 11)
- MAD: Maximum thrombin generation (peak height)(From Day 10 to Day 11)
- SSD: Change in D-dimer(From baseline (Day 1) to Day 36)
- SSD: Change in fibrinogen(From baseline (Day 1) to Day 36)
- SSD: Change in prothrombin fragment 1 and 2(From baseline (Day 1) to Day 36)
- SSD: AUC, SD: the area under the concentration curve of Inno8 after a single dose(From baseline (Day 1) to Day 36)
- SSD: T1/2, SD: the terminal half-life of Inno8 after a single dose(From baseline (Day 1) to Day 36)
- SSD: Change in platelets(From baseline (Day 1) to Day 36)
- SSD: Cmax, SD: the maximal concentration of Inno8 after a single dose(From baseline (Day 1) to Day 36)
- SSD: Maximum change in activated partial thromboplastin time(From baseline (Day 1) to Day 36)
- SSD: Maximum thrombin generation (peak height)(From baseline (Day 1) to Day 36)