NCT05288673已完成1 期
A Phase 1, Randomized, Blinded, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics 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
- 16
- 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 and tolerability of multiple doses of ALXN1210 (400 and 800 milligrams [mg]) following intravenous (IV) administration to healthy participants.
详细描述
Participants were divided into 2 cohorts and were randomly assigned in a 3:1 ratio to receive IV ALXN1210 or placebo. Participants in Cohort 1 received 5 IV doses of 400 mg of ALXN1210 or placebo administered every 28 days. To determine if dose continuation and dose escalation to Cohort 2 should occur, the Safety Review Committee conducted a blinded review of the available safety data after Day 15 of the second dose of the last participant in Cohort 1. Participants in Cohort 2 received 5 doses of 400 mg of ALXN1210 or placebo and 5 IV doses of 800 mg of ALXN1210 or placebo administered intravenously every 28 days. Safety, PK, PD, and immunogenicity assessments were performed during the Follow-up Period after the last dose.
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 who prepared ALXN1210 or placebo, however, was not blinded to study drug assignment, but all other site staff, including the Investigator and personnel administering study drug, was blinded. Sponsor staff was unblinded as needed (for example, to monitor the pharmacy), but did not share 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
- •Healthy male and female participants ≥ 25 and ≤ 55 years old; smokers (no more than 10 cigarettes daily), former smokers (at the Investigator's discretion), or nonsmokers.
- •Body mass index from 18 through 29.9 kilogram (kg)/square meter, inclusive, and weight between 50 and 100 kg, inclusive.
- •QT interval (corrected using the Fridericia formula) ≤ 450 milliseconds (ms) for males and ≤ 470 ms for females at Screening and prior to dosing on Day
- •Participant was willing and able to give written informed consent and comply with the study visit schedule.
- •Documented vaccination with tetravalent meningococcal conjugate vaccine (MCV4) at least 56 days and not more than 3 years prior to dosing. Documentation must have included a positive serum bactericidal antibody test to confirm an immune response before the study drug administration.
- •Vaccination with serogroup B vaccine at least 56 days prior to dosing on Day 1, with a booster administered at least 28 days prior to dosing on Day
- •Male participants with a female spouse/partner of childbearing potential or a pregnant or breastfeeding spouse or partner were required to use barrier contraception (male condom) during the treatment period and for at least 6 months after the last dose of ALXN1210.
排除标准
- •Participants who had intimate and prolonged contact (defined as living under the same roof or providing personal care) with individuals who were either immunocompromised, or had specific underlying medical conditions (persons with anatomic or functional asplenia [including sickle cell disease]; persons with congenital complement, properdin, factor D, or primary antibody deficiencies, persons with acquired complement deficiencies [for example, those receiving eculizumab], and persons with human immunodeficiency virus [HIV]) or with persons younger than 2 years of age or older than 65 years of age
- •Participants who were one of the following: professionals exposed to environments of greater risk for meningococcal disease; research, industrial, and clinical laboratory personnel 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; those living on a college or university campus; or those who planned to travel during the course of the study to or had travelled to endemic areas for meningococcal meningitis (for example, India, Sub-Saharan Africa, pilgrimage to Saudi Arabia for Hajj) within the past 6 months
- •History of any Neisseria infection
- •History of unexplained recurrent infection or infection that required treatment with systemic antibiotics within the last 90 days prior to dosing
- •HIV infection (evidenced by HIV-1 or HIV-2 antibody titer)
- •Acute or chronic hepatitis B virus infection (evidenced by the presence of hepatitis B surface antigen or immunoglobulin M antibodies against hepatitis B core antigen)
- •Acute or chronic hepatitis C virus infection (evidenced by antibody titer)
- •Active systemic viral or fungal infection within 14 days prior to dosing
- •Positive or indeterminate QuantiFERON-TB test indicating possible tuberculosis infection
- •History of latent or active tuberculosis or exposure to endemic areas within 8 weeks prior to the screening visit
- •Female participants who were breastfeeding or were of childbearing potential, including any female who had experienced menarche and who had not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who was pregnant, breastfeeding, or not postmenopausal.
- •Positive serum pregnancy test at Screening or Day -1
- •Serum creatinine > upper limit of normal (ULN) of the reference range of the testing laboratory at Screening or Day -
- •Alanine aminotransferase or aspartate aminotransferase > ULN of the reference range of the testing laboratory at Screening or > 1.5*ULN of the reference range of the testing laboratory at Day -
- •Any of the following hematology results: 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 reference range; absolute neutrophils < 1.5*10^3/μL (< 1.0*10^3/μL for black race participants) or > ULN of the testing laboratory reference range; and platelets < the lower limit of normal of the testing laboratory reference range or > 450*10^3/μL at Screening or Day -1; or complete blood count clinical laboratory results considered as clinically relevant and unacceptable by the Investigator at Day -
- •History of complement deficiency or complement activity below normal reference range as evaluated by complement alternative pathway enzyme-linked immunosorbent assay at Screening.
- •History of malignancy, other than basal cell carcinoma that had been treated and had no evidence of recurrence.
- •Participation in a clinical study within 30 days before initiation of dosing on Day 1 or use of any experimental small-molecule therapy within 30 days prior to dosing on Day
- •Participation in more than 1 clinical study of a monoclonal antibody (mAb) or participation in a clinical study of a mAb within the 12 months prior to Screening during which the participant was exposed to the active study drug. Participants who had participated in only 1 study of an mAb were considered for enrollment if they had completed that study more than 12 months prior to Screening.
- •Major surgery or hospitalization within 90 days prior to dosing.
- •Contraindication to receiving MCV4 and/or serogroup B vaccine, including severe (life-threatening) allergic reaction to a previous dose of MCV4 and/or serogroup B vaccine, severe (life-threatening) allergy to any vaccine component, or previous diagnosis of Guillain-Barré syndrome.
- •History of allergy to excipients of ALXN1210 (that is, polysorbate 80).
- •Documented history of allergy to penicillin or cephalosporin.
- •History of significant allergic reaction (anaphylaxis, angioedema) to any product (food, pharmaceutical, etc).
- •Positive urine drug toxicology screen at Screening or Day -
- •Donation of plasma within 7 days prior to dosing. Donation or loss (excluding volume drawn at Screening) of more than 50 mL of blood within 30 days of dosing or more than 499 mL of blood within 56 days of dosing.
- •Use of prescription medications within 28 days prior to study drug administration.
- •Clinical diagnosis of any autoimmune or rheumatologic disease (for example, systemic lupus erythematosus, rheumatoid arthritis).
- •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 (confirmed body temperature > 37.6°C; for example, a fever associated with a symptomatic viral or bacterial infection) within 14 days prior to the first dose.
- •Participants with any medical history, conditions or risks that, in the opinion of the Investigator, would have interfered with the participant's full participation in the study or compliance with the protocol, posed any additional risk for the participant, or confounded the assessment of the participant or outcome of the study.
研究组 & 干预措施
ALXN1210 400 mg
Experimental
Participants received ALXN1210 every 28 days.
干预措施: ALXN1210 (Drug)
ALXN1210: 800 mg
Experimental
Participants received ALXN1210 every 28 days.
干预措施: ALXN1210 (Drug)
Placebo
Placebo Comparator
Participants received placebo every 28 days.
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 309
An adverse event (AE) was defined as any unfavorable and unintended sign (for example, including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or procedure, whether or not considered related to the medicinal product or procedure, which occurred during the course of the clinical study. 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
- Area Under The Serum Concentration Versus Time Curve From Time Zero To Infinity (AUCinf) of ALXN1210(Predose, end of infusion, 30 minutes, 4 hours, 8 hours and 24 hours post start of infusion on Day 1 up to Day 309)
- Area Under The Serum Concentration From Time Zero To The Time of The Last Quantifiable Concentration (AUCt) of ALXN1210(Predose, end of infusion, 30 minutes, 4 hours, 8 hours and 24 hours post start of infusion on Day 1 up to Day 309)
- Maximum Observed Serum Concentration (Cmax) of ALXN1210(Predose, end of infusion, 30 minutes, 4 hours, 8 hours and 24 hours post start of infusion on Day 1 up to Day 309)
- Percent Change From Baseline in Free Complement Protein C5 Concentration at Day 113(Baseline, Day 113)
- Percent Change From Baseline in Total C5 Concentration at Day 113(Baseline, Day 113)
- Percent Change From Baseline in Chicken Red Blood Cell Hemolysis at Day 113(Baseline, Day 113)
- Percent Change From Baseline in C5 Activation at Day 113(Baseline, Day 113)
- Number of Participants With Positive Antidrug Antibodies (ADAs) to ALXN1210(Baseline up to Day 309)
研究者
研究点 (1)
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