NCT05288660已完成1 期
A Phase 1, Randomized, Blinded, Placebo Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Dose of ALXN1210 Administered Intravenously to Healthy Subjects
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
This study evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a single dose of ALXN1210 in healthy participants, as assessed by electrocardiograms, physical examination, vital signs, laboratory analysis, and assessment of adverse events (AEs).
详细描述
The participants were randomized in a 2:1 ratio (4 active and 2 placebo) to receive a single dose of ALXN1210 or placebo in the 200-milligram (mg) dose cohort and in a 3:1 ratio (6 active and 2 placebo) to receive a single dose of ALXN1210 or placebo in the 400-mg dose cohort, administered by intravenous (IV) infusion. A 150-day observation period was performed for safety, pharmacokinetic, and pharmacodynamic assessments after study drug administration. Antidrug antibody (ADA) levels were monitored in study participants for the duration of the 150-day follow-up period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Participants and on-site medical/nursing staff at the study site were blinded to study drug/dose assignment. The pharmacy staff preparing the investigational products, however, were not blinded to ALXN1210 study drug assignment, but all other site staff, including the Investigator, were blinded. Sponsor staff was unblinded as needed (for example, to participate in the Safety Review Committee and to determine reportability of serious adverse events [AEs]), but was to refrain from sharing any information on study drug assignment with the site staff.
入排标准
- 年龄范围
- 25 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Body mass index from 18 through 29.9 kilogram (kg)/square meter, inclusive, and weight between 50 and 100 kg, inclusive.
- •QT interval (Fridericia's correction); ≤450 milliseconds (msec) for males and ≤470 msec for females at screening and pre-dose on Day
- •Willing and able to give written informed consent and comply with the study visit schedule.
- •Male participant and his female spouse/partner who was of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (at least 1 of which must be a barrier method), starting at screening and continuing until at least 5 months after the last dose of ALXN
- •Documented vaccination with meningococcal conjugate vaccine (MCV4) at least 14 days and not more than 3 years prior to dosing.
排除标准
- •Participants in intimate and prolonged contact (defined as living under the same roof or providing personal care) with individuals who are either immunocompromised, or with a specific underlying medical conditions (anatomic or functional asplenia [including sickle cell disease]; congenital complement, properdin, factor D, or primary antibody deficiencies; acquired complement deficiencies [for example, those receiving eculizumab]; and human immunodeficiency virus [HIV]), people younger than 2 years old and older than 65 years old, and professionals exposed to environments of greater risk for meningococcal disease (research, industrial, and clinical laboratory personnel who are routinely exposed to Neisseria meningitidis, military personnel during recruit training [military personnel may be at increased risk when accommodated in close quarters], daycare center workers, or those living on a college or university campus).
- •Participants living or working in the Saguenay-Lac-St-Jean area (due to increased incidence of meningococcal infections in that specific area).
- •Female participants of childbearing potential, including any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), or who was pregnant, breastfeeding, or was not postmenopausal.
- •Positive serum pregnancy test at screening or Day -
- •Serum creatinine greater than the upper limit of normal (ULN) of the testing laboratory at screening and Day -
- •Alanine aminotransferase or aspartate aminotransferase >ULN of the testing laboratory at screening and Day -
- •Any of the following hematology tests: hemoglobin <135 grams (g)/L for males and <120 g/L for females; hematocrit <0.41 L/L for males and <0.36 L/L for females; white blood cells <3.5*10^3/microliter (μL) or >ULN of the testing laboratory; absolute neutrophils <1.5*10^3/μL (<1.0*10^3/μL for black race volunteers) or >ULN of the testing laboratory; and platelets <the lower limit of normal of the testing laboratory or >450*10^3/μL at screening and Day -
- •HIV infection (evidenced by HIV-1 or HIV-2 antibody titer).
- •Acute or chronic hepatitis B virus (HBV) infection (evidenced by the presence of HBV surface antigen or immunoglobulin M antibodies against HBV core antigen).
- •Acute or chronic hepatitis C virus infection (evidenced by antibody titer).
- •Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing.
- •Positive QuantiFERON-TB test, indicating possible tuberculosis (TB) infection.
- •History of complement deficiency.
- •History of malignancy other than basal cell carcinoma.
- •Participated in a clinical trial within 30 days before initiation of dosing on Day 1, or used any experimental small-molecule therapy within 30 days prior to dosing on Day 1, or biologic therapy within 90 days prior to initiation of dosing on Day 1 or within 5 half-lives of the product, whichever is greater.
- •Major surgery within the last 90 days prior to dosing.
- •History of any Neisseria infection; history of unexplained, recurrent infection; or infection requiring treatment with systemic antibiotics within the last 90 days prior to dosing.
- •Contraindication to receiving MCV4, including severe (life-threatening) allergic reaction to a previous dose of MCV4; severe (life-threatening) allergy to any vaccine component; previous diagnosis of Guillain-Barré Syndrome.
- •History of allergy to excipients of ALXN1210 (that is, polysorbate 80)
- •History of allergy to penicillin or cephalosporin, or history of significant allergic reaction to other products (anaphylaxis and angioedema).
- •Positive urine drug toxicology screen.
- •Donation of plasma within 7 days prior to dosing. Donation or loss of blood of more than 50 mL of blood within 30 days of dosing, or more than 499 mL of blood within 56 days of dosing.
- •Clinical diagnosis of any autoimmune or rheumatologic disease (for example, systemic lupus erythematosus, and rheumatoid arthritis) or other condition or medical history that, in the opinion of the Investigator, might interfere with the participant's participation in the study, poses an added risk for the participant, or confounds the assessment of the participant or outcome of the study.
- •History of latent or active TB or exposure to endemic areas within 8 weeks prior to the TB test performed at screening.
- •Immunization with a live attenuated vaccine 1 month prior to dosing or planned vaccination during the course of the study (except for the vaccination planned by the study protocol).
- •Presence of fever (body temperature > 37.6°C) (for example, a fever associated with a symptomatic viral or bacterial infection) within 2 weeks prior to the first dosing.
研究组 & 干预措施
ALXN1210 200 mg
Experimental
ALXN1210 was administered intravenously.
干预措施: ALXN1210 (Drug)
ALXN1210 400 mg
Experimental
ALXN1210 was administered intravenously.
干预措施: ALXN1210 (Drug)
Placebo
Placebo Comparator
Placebo was administered intravenously.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
时间窗: Baseline up to Day 150
TEAEs were defined as AEs that occurred on or after the date and time of study drug administration, or those that first occurred before dosing but worsened in frequency or severity after study drug administration. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
次要结局
- Terminal Elimination Half-life (t½) of Serum ALXN1210(Predose, 30 minutes, 4, 8, 24, 48, 96 hours postdose, then at Days 8, 15, 22, 29, 36, 43, 50, 57, 71, 90, 120 and 150)
- Total Clearance (CL) of ALXN1210(Predose, 30 minutes, 4, 8, 24, 48, 96 hours postdose, then at Days 8, 15, 22, 29, 36, 43, 50, 57, 71, 90, 120 and 150)
- Volume of Distribution (Vd) of ALXN1210(Predose, 30 minutes, 4, 8, 24, 48, 96 hours postdose, then at Days 8, 15, 22, 29, 36, 43, 50, 57, 71, 90, 120 and 150)
- Percent Change From Baseline in Free Complement Component 5 (C5)(Baseline, Day 150)
- Percent Change From Baseline in Total Complement C5(Baseline, Day 150)
- Area Under The Serum Concentration Versus Time Curve From Time Zero (Dosing) To Infinity (AUCinf) of ALXN1210(Predose, 30 minutes, 4, 8, 24, 48, 96 hours postdose, then at Days 8, 15, 22, 29, 36, 43, 50, 57, 71, 90, 120 and 150)
- Percent Change From Baseline in Complement C5b-9(Baseline, Day 8)
- Percent Change From Baseline in Chicken Red Blood Cell Hemolysis(Baseline, Day 150)
- Percent Change From Baseline In Complement Classical Pathway (CCP) Activity(Baseline, Day 150)
- Percent Change From Baseline In Complement Alternative Pathway (CAP) Activity(Baseline, Day 150)
- Percentage of Participants With Positive Anti-Drug Antibody (ADA)(Baseline up to Day 150)
- Maximum Observed Serum Concentration (Cmax) of ALXN1210(Predose, 30 minutes, 4, 8, 24, 48, 96 hours postdose, then at Days 8, 15, 22, 29, 36, 43, 50, 57, 71, 90, 120 and 150)
- Time To Maximum Observed Serum Concentration (Tmax) of ALXN1210(Predose, 30 minutes, 4, 8, 24, 48, 96 hours postdose, then at Days 8, 15, 22, 29, 36, 43, 50, 57, 71, 90, 120 and 150)
- Area Under The Serum Concentration Versus Time Curve From Time Zero To The Time of The Last Quantifiable Concentration (AUC0-t) of ALXN1210(Predose, 30 minutes, 4, 8, 24, 48, 96 hours postdose, then at Days 8, 15, 22, 29, 36, 43, 50, 57, 71, 90, 120 and 150)
- Terminal Elimination Rate Constant (λz) of Serum ALXN1210(Predose, 30 minutes, 4, 8, 24, 48, 96 hours postdose, then at Days 8, 15, 22, 29, 36, 43, 50, 57, 71, 90, 120 and 150)
研究者
研究点 (1)
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