A Placebo-controlled, Within-group Randomised, and Double-blind Trial Investigating Safety, Tolerability, and Pharmacokinetics of FE 999301 After Ascending Single and Multiple Doses in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Change in clinical chemistry from baseline to Day 36 after a single dose infusion
研究概览
简要总结
Interleukin (IL)-6 is a cytokine produced in response to infection and tissue damage. IL-6 is believed to act as a key mediator in chronic inflammation and autoimmune diseases such as inflammatory bowel diseases. IL-6 is known to be involved in at least two distinct signalling pathways, classical and trans-signalling. The hypothesis is that classical signalling by IL-6 infers some beneficial effects (e.g. on gut barrier function), while excessive IL-6 trans-signalling may have detrimental effects. Olamkicept (FE 999301) has been shown in vitro to be a selective IL-6 trans-signalling inhibitor, and administered at lower doses (600 mg every 2nd week for 12 weeks) it has proven to induce clinical improvement for patients with ulcerative colitis. The aim of this trial is to investigate safety, tolerability, immunogenicity and pharmacokinetics of Olamkicept at higher doses (up to 2400 mg) to support the clinical development program. Our hypothesis is that treatment with higher doses of Olamkicept will result in greater clinical improvement for patients with inflammatory bowel diseases.
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)
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
- •Men ≥18 and ≤45 years of age at screening
- •In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), vital signs measurements, and clinical laboratory evaluations, as assessed by the investigator (or designee) at screening and on Day -1
排除标准
- •History of clinically significant medical conditions including, but not limited to, diseases of the renal, hepatic, respiratory, gastrointestinal, cardiovascular, neurological, musculoskeletal, psychiatric, immunological, haematological, oncological, endocrine, and metabolic systems and allergic diseases (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
研究组 & 干预措施
Placebo - Part B
干预措施: Placebo (Drug)
Olamkicept - Part A
干预措施: Olamkicept Part A (Drug)
Placebo - Part A
干预措施: Placebo (Drug)
Olamkicept - Part B
干预措施: Olamkicept Part B (Drug)
结局指标
主要结局
Change in clinical chemistry from baseline to Day 36 after a single dose infusion
时间窗: From baseline to Day 36 after a single dose infusion
Number of participants with clinically significant abnormal findings in clinical chemistry (alanine aminotransferase (ALT), albumin, alkaline phosphatase, aspartate aminotransferase (AST), glucose, calcium, chloride, cholesterol, C-reactive protein, creatinine, estimated glomerular filtration rate (eGFR), gamma-glutamyltransferase, phosphate, potassium, sodium, thyroid stimulating hormone, free triiodothyronine, free thyroxine, total bilirubin, urea (blood urea nitrogen)), from baseline up to and including Day 36 after a single dose infusion (part A of the study)
Change in haemostasis parameters from baseline to Day 64 after multiple dose infusions
时间窗: From baseline up to and including Day 64 after multiple dose infusions
Number of participants with clinically significant abnormal findings in haemostasis parameters (activated partial thromboplastin time, prothrombin time) from baseline up to and including Day 64 after multiple dose infusions (part B of the study)
Change in 12-lead electrocardiogram (ECG) from baseline to Day 36 after a single dose infusion
时间窗: From baseline up to and including Day 36 after a single dose infusion
Number of participants with clinically significant abnormal findings in ECG (heart rate, PR interval, RR, QRS duration, QT interval, QTc interval, QRS axis), from baseline up to and including Day 36 after a single dose infusion (part A of the study)
Change in 12-lead electrocardiogram (ECG) from baseline to Day 64 after multiple dose infusions
时间窗: From baseline up to and including Day 64 after multiple dose infusions
Number of participants with clinically significant abnormal findings in ECG (heart rate, PR interval, RR, QRS duration, QT interval, QTc interval, QRS axis), from baseline up to and including Day 64 after multiple dose infusions (part B of the study)
Change in haematology from baseline to Day 64 after multiple dose infusions
时间窗: From baseline to Day 64 after multiple dose infusions
Number of participants with clinically significant abnormal findings in haematology (haematocrit, haemoglobin, mean cellular volume (MCV), mean corpuscular haemoglobin content (MCH), mean corpuscular haemoglobin concentration (MCHC), platelet count, red blood cell count, reticulocytes, white blood cell count with differential count, neutrophils, eosinophils, basophils, lymphocytes, monocytes), from baseline up to and including Day 64 after multiple dose infusions (part B of the study)
Change in clinical chemistry from baseline to Day 64 after multiple dose infusions
时间窗: From baseline up to and including Day 64 after multiple dose infusions
Number of participants with clinically significant abnormal findings in clinical chemistry (alanine aminotransferase (ALT), albumin, alkaline phosphatase, aspartate aminotransferase (AST), glucose, calcium, chloride, cholesterol, C-reactive protein, creatinine, estimated glomerular filtration rate (eGFR), gamma-glutamyltransferase, phosphate, potassium, sodium, thyroid stimulating hormone, free triiodothyronine, free thyroxine, total bilirubin, urea (blood urea nitrogen)), from baseline up to and including Day 64 after multiple dose infusions (part B of the study)
Change in urinalysis parameters from baseline to Day 36 after a single dose infusion
时间窗: From baseline to Day 36 after a single dose infusion
Number of participants with clinically significant abnormal findings in urinalysis parameters (protein, glucose, bilirubin, pH, nitrite, ketone, urobilinogen, blood, leukocytes, specific gravity) from baseline up to and including Day 36 after a single dose infusion (part A of the study)
Number of treatment-emergent adverse events, including type, intensity, and causality
时间窗: End of trial (up to 64 days)
Change in vital signs from baseline to Day 36 after a single dose infusion
时间窗: From baseline up to and including Day 36 after a single dose infusion
Number of participants with clinically significant abnormal findings in vital signs (systolic blood pressure, diastolic blood pressure, pulse, body temperature), from baseline up to and including Day 36 after a single dose infusion (part A of the study).
Change in haematology from baseline to Day 36 after a single dose infusion
时间窗: From baseline to Day 36 after a single dose infusion
Number of participants with clinically significant abnormal findings in haematology (haematocrit, haemoglobin, mean cellular volume (MCV), mean corpuscular haemoglobin content (MCH), mean corpuscular haemoglobin concentration (MCHC), platelet count, red blood cell count, reticulocytes, white blood cell count with differential count, neutrophils, eosinophils, basophils, lymphocytes, monocytes), from baseline up to and including Day 36 after a single dose infusion (part A of the study)
Change in vital signs from baseline to Day 64 after multiple dose infusions
时间窗: From baseline up to and including Day 64 after multiple dose infusions
Number of participants with clinically significant abnormal findings in vital signs (systolic blood pressure, diastolic blood pressure, pulse, body temperature), from baseline up to and including Day 64 after multiple dose infusions (part B of the study)
Change in urinalysis parameters from baseline to Day 64 after multiple dose infusions
时间窗: From baseline up to and including Day 64 after multiple dose infusions
Number of participants with clinically significant abnormal findings in urinalysis parameters (protein, glucose, bilirubin, pH, nitrite, ketone, urobilinogen, blood, leukocytes, specific gravity) from baseline up to and including Day 64 after multiple dose infusions (part B of the study)
Change in haemostasis parameters from baseline to Day 36 after a single dose infusion
时间窗: From baseline up to and including Day 36 after a single dose infusion
Number of participants with clinically significant abnormal findings in haemostasis parameters (activated partial thromboplastin time, prothrombin time) from baseline up to and including Day 36 after a single dose infusion (part A of the study)
次要结局
- Single-dose PK of FE 999301: Baseline adjusted maximum observed concentration; also referred to as maximum exposure (Cmax)(From baseline up to and including Day 36 after a single dose infusion)
- Single-dose PK of FE 999301: Area under the concentration-time curve from dosing to infinity (AUCinf)(From baseline up to and including Day 36 after a single dose infusion)
- Single-dose PK of FE 999301: Apparent volume of distribution at steady-state (Vss)(From baseline up to and including Day 36 after a single dose infusion)
- Single-dose PK of FE 999301: Mean residence time (MRT)(From baseline up to and including Day 36 after a single dose infusion)
- Single-dose PK of FE 999301: Time of maximum observed concentration (tmax)(From baseline up to and including Day 36 after a single dose infusion)
- Single-dose PK of FE 999301: Terminal half-life (t1/2)(From baseline up to and including Day 36 after a single dose infusion)
- Single-dose PK of FE 999301: Total clearance (CL)(From baseline up to and including Day 36 after a single dose infusion)
- Multiple-dose PK of FE 999301: Observed accumulation index (Rac)(From baseline up to and including Day 64 after a multiple dose infusions)
- Multiple-dose PK of FE 999301: Apparent volume of distribution at steady-state (Vss)(Day 64)
- Multiple-dose PK of FE 999301: Baseline adjusted maximum observed concentration; also referred to as maximum exposure (Cmax)(From baseline up to and including Day 64 after a multiple dose infusions)
- Multiple-dose PK of FE 999301: Total clearance (CL)(From baseline up to and including Day 64 after a multiple dose infusions)
- Multiple-dose PK of FE 999301: Area under concentration-time curve from dosing up to time τ, where τ is the dosing interval (AUCτ)(From baseline up to and including Day 64 after a multiple dose infusions)
- Multiple-dose PK of FE 999301: Observed plasma concentration at end of infusion (Ceio)(From baseline up to and including Day 64 after a multiple dose infusions)
- Multiple-dose PK of FE 999301: Time of maximum observed concentration (tmax)(From baseline up to and including Day 64 after a multiple dose infusions)
- Multiple-dose PK of FE 999301: Terminal half-life (t½)(From baseline up to and including Day 64 after a multiple dose infusions)
- Single-dose PK of FE 999301: Area under the concentration-time curve to last measurable concentration (AUClast)(From baseline up to and including Day 36 after a single dose infusion)
- Single-dose PK of FE 999301: Observed plasma concentration at end of infusion (AUCeoi)(From baseline up to and including Day 36 after a single dose infusion)
- Multiple-dose PK of FE 999301: Area under the concentration-time curve to last measurable concentration (AUClast)(From baseline up to and including Day 64 after a multiple dose infusions)
- Multiple-dose PK of FE 999301: Mean residence time (MRT)(From baseline up to and including Day 64 after a multiple dose infusions)
- Presence of anti-FE 999301 antibodies on Days 1, 15, and 57 after multiple dose infusions(On Days 1, 15, and 57 after multiple dose infusions)