A Randomized, Double-blinded, Placebo-controlled, Single Center, Phase I Study to Evaluate Pharmacokinetics, Pharmacodynamics and Safety of Emapalumab After a Single Intravenous Dose in Japanese Healthy Volunteers.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Concentration of Emapalumab at End of Infusion
研究概览
简要总结
This is a randomized, placebo controlled and double-blinded study to evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and safety of a single dose (1 mg/kg) of emapalumab in adult healthy Japanese subjects.
详细描述
This is a randomized, placebo-controlled and double-blinded study to evaluate the PK, PD and safety of a single dose (1 mg/kg) of emapalumab in adult healthy Japanese subjects, performed in Japan. The subjects, 8 in total, will be randomized to receive either emapalumab or matching placebo in a 3:1 ratio (emapalumab: placebo).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Single (Care Provider)
盲法说明
Double blind
入排标准
- 年龄范围
- 20 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy Japanese (male and female) subjects between 20 and 50 years (inclusive).
- •Body weight greater than 45 kg (female) or 50 kg (male) and a body mass index (BMI) >18 kg/m2 and < 30 kg/m2 (BMI= weight (kg) / height (m)²)
- •Vital signs in the following range:
- •Axillary body temperature: 35.2 - 37.5℃
- •Heart rate (after at least 3 minutes of rest, measured in the supine position): 40-100 bpm
- •BP < 140/80, mean of 3 readings after 15 minutes rest
- •Haemoglobin level equal or above 11 g/dL in females and 13 g/dL in males.
- •Subject having C-reactive protein (CRP) levels within the normal range (local laboratory range).
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant having agreed to use highly effective methods of contraception during dosing and for 6 months after receiving IMP.
- •Highly effective contraception methods include:
- •Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- •Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
- •Male sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient, otherwise highly effective methods to be applied.
- •Use of oral (estrogen and progesterone) hormonal method of contraception, or placement of an intrauterine device (IUD) or intrauterine system (IUS)
- •In case of use of oral contraception women should have been stable on the same brand (or generic equivalent) for a minimum of 3 months before taking study treatment.
- •Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago.
- •Signed informed consent.
排除标准
- •Any clinically significant abnormality in the results of the safety laboratory tests. Subjects presenting a minor deviation from laboratory ranges could be enrolled if the investigator judge it to be non-clinically significant
- •Any clinically significant abnormality on the screening electrocardiogram (ECG), as judged by the investigator
- •History or clinical evidence of any disease and/or existence of any surgical or medical condition that might interfere with the absorption, distribution, metabolism or excretion of the study drugs
- •Actual presence or occurrence of any bacterial, viral, parasitic or fungal infection within the 4 weeks preceding IMP infusion
- •Positive results from serology examination for Hepatitis B surface antigen (HBsAg), Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV), syphilis (TP-antigen and RPR) or pregnancy
- •Positive stool test for Shigella or salmonella infection.
- •Positive results from Sars-CoV-2 screening within 96 hours prior to randomization
- •History or clinical evidence suggestive of active or latent tuberculosis at screening. (i.e. test positive to the interferon gamma (IFNγ)-release assay)
- •History or presence of any severe allergic reactions
- •History of hypersensitivity or allergy to any component of emapalumab and/or valaciclovir hydrochloride
- •History or presence of any malignancy
- •History or presence of drug or alcohol abuse
- •Subject with a smoking history within the last 6 months prior to the time of screening
- •Immunization with a live vaccine within 6 weeks prior to receiving IMP and 12 weeks after IMP infusion
- •Experience of collected blood corresponding to any of the following
- •Component blood donation within 2 weeks before the screening test and within 2 weeks before the first study drug administration
- •Collection of 200 mL or more of blood (blood donation, etc.) from 4 weeks before the screening test until admission
- •Male subject who has experience of collection of 400 mL or more of blood (blood donation, etc.) from 12weeks before the screening test until admission.
- •Female subject who has experience of collection of 400 mL or more of blood (blood donation, etc.) from 16weeks before the screening test until admission.
- •Usage of any prescription drugs within 2 weeks or over-the-counter medication including herbal supplements (with the exception of multi-vitamins) within 1 week before IMP administration without prior approval from the investigator
- •Positive pregnancy test at screening or Day -1
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol
- •Enrollment in another concurrent clinical interventional study, or intake of another IMP, within four months or 5 half-lives (of the other IMP) prior to inclusion in this study
研究组 & 干预措施
emapalumab
emapalumab i.v infusion
干预措施: NI-0501 (Drug)
Placebo
Saline i.v. infusion
干预措施: Saline (Drug)
结局指标
主要结局
Concentration of Emapalumab at End of Infusion
时间窗: Day 1 preinfusion, 1hr, 2 hrs, 4hrs, 8hrs, 10hrs, Day 2, 3, 5, 8, Week 2, 4, 6, 8, 10, 12, study completion week 14 or at Withdrawal
Concentration of emapalumab at end of infusion (CEnd of inf))
The Maximum Observed Concentration of Emapalumab
时间窗: Day 1 preinfusion, 1hr, 2hrs, 4hrs, 8hrs, 10hrs post dose, day 2, 3, 5, 8, week 2, 4, 6, 8, 10, 12, study completion week 14 or Withdrawal
The maximum observed concentration of emapalumab (Cmax)
The Time at Which the Maximum Concentration of Emapalumab is Observed
时间窗: Day 1 preinfusion, 1hr, 2 hrs, 4hrs, 8hrs, 10hrs, Day 2, 3, 5, 8, Week 2, 4, 6, 8, 10, 12, study completion week 14 or at Withdrawal
The time at which the maximum concentration of emapalumab is observed (Tmax)
Area Under the Plasma Concentration-time Curve
时间窗: Day 1 preinfusion, 1hr, 2 hrs, 4hrs, 8hrs, 10hrs, Day 2, 3, 5, 8, Week 2, 4, 6, 8, 10, 12, study completion week 14 or at Withdrawal
Area under the plasma concentration-time curve from emapalumab injection to time of last measurable concentration (AUClast)
Area Under the Concentration-time Curve Extrapolated to Infinity
时间窗: Day 1 preinfusion, 1hr, 2 hrs, 4hrs, 8hrs, 10hrs, Day 2, 3, 5, 8, Week 2, 4, 6, 8, 10, 12, study completion week 14 or at Withdrawal
Area under the plasma concentration-time curve from emapalumab injection extrapolated to infinity (AUCinf)
Emapalumab Elimination Half-life
时间窗: Day 1 preinfusion, 1hr, 2 hrs, 4hrs, 8hrs, 10hrs, Day 2, 3, 5, 8, Week 2, 4, 6, 8, 10, 12, study completion week 14 or at Withdrawal
Emapalumab elimination half-life (t1/2)
Apparent Total Body Clearance of Emapalumab From Plasma
时间窗: Day 1 preinfusion, 1hr, 2 hrs, 4hrs, 8hrs, 10hrs, Day 2, 3, 5, 8, Week 2, 4, 6, 8, 10, 12, study completion week 14 or at Withdrawal
Apparent total body clearance of emapalumab from plasma (CL)
Steady State Volume of Distribution
时间窗: Day 1 preinfusion, 1hr, 2 hrs, 4hrs, 8hrs, 10hrs, Day 2, 3, 5, 8, Week 2, 4, 6, 8, 10, 12, study completion week 14 or at Withdrawal
Apparent volume of distribution at steady state (Vss)
次要结局
- Change in Levels of Alkaline Phosphatase(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Total Protein(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Albumin(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Sodium(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of BUN/Urea Haematology(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Hemoglobin(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Platelet Count(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Neutrophils(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Red Blood Cells(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Immunoglobulin Levels(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Coagulation Profile(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Presence of Anti-drug Antibodies and Neutralizing Antibodies(From Day 1 to Week 14)
- Change in Levels of Complement C4(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Presence of Neutralizing Antibodies(From Day 1 to Week 14)
- Overall Summary of Adverse Events(Continuously from start of emapalumab infusion up to 14 weeks)
- Change in Levels of Aspartate Aminotransferase(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Alanine Aminotransferase(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Direct Bilirubin(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Total Bilirubin(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Uric Acid(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Prothrombin Time/International Normalized Ratio(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Fibrinogen(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Complement C3(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Creatinine(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of C-reactive Protein(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Potassium(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Glucose(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of HDL(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Hematocrit(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of Calcium(Baseline, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))
- Change in Levels of LDL(Baselilne, Days 1,2,3,5,8, Weeks 2,4,6,10, and Study Completion Visit (Week 14))