A Phase 1, Open-label, Randomized, Parallel-group Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, Immunogenicity, and Device Performance of ALXN1720 (Gefurulimab) Administered Subcutaneously Using Prefilled Syringe Versus Autoinjector in Adult Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 175
- 试验地点
- 1
- 主要终点
- Maximum (peak) concentration observed after study intervention administration (Cmax)
研究概览
简要总结
This study will evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, immunogenicity, and device performance of gefurulimab.
详细描述
This is an open-label, randomized, parallel-group study.
The study consists of 2 periods: a Screening Period (up to 70 days), and an Evaluation Period of 92 days.
Separate randomization lists will be produced for each weight stratum (50 to < 70 kg, 70 to < 90 kg, and 90 to < 110 kg) and within each of the three weight strata, participants will be randomized 1:1:1:1:1:1 to one of the six combinations of device (prefilled syringe with needle safety device [PFS-SD] or autoinjector [AI]) and injection site (abdomen, thigh, or upper arm),
Participants will receive a single dose of 600 mg gefurulimab on Day 1, will be residential at the clinical unit until Day 5, will have visits on Day 8, quaque week (once a week) [qw] thereafter until Day 50, and quaque 2 week (once every two weeks) [q2w] from Day 50 until Day 92 during the Evaluation Period.
The total study duration is up to 162 days.
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
- Single (Outcomes Assessor)
盲法说明
This is an open-label study. To avoid potential bias and maintain the data integrity, the analysis and reporting performed before database lock for Primary Analysis, ie, dry run/blinded data review for Primary Analysis, will be based on blinded data in which the treatment information is based on a dummy randomization schedule.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
- •Body weight within ≥ 50 to < 110 kg and body mass index (BMI) within the range 18.5 to 30 kg/m2 (inclusive)
- •Participants who are healthy as determined by medical evaluation with no clinically significant or relevant abnormalities as determined by medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory evaluation.
- •QT interval corrected using Fridericia's formula (QTcF) ≤ 450 msec for male participants and ≤ 460 msec for female participants at Screening and prior to dosing on Day
- •Documented vaccination against meningococcal infection from serogroups A, C, W, and Y and serogroup B.
- •Male and female participants should adhere to study-specific contraceptive methods.
排除标准
- •History of any Neisseria meningitidis infection.
- •History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders.
- •Abnormal blood pressure as determined by the Investigator.
- •History of latent or active TB (Tuberculosis) or exposure to endemic areas.
- •Allergy to monoclonal antibodies.
- •Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe posttreatment hypersensitivity reactions.
- •Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
- •Current or chronic history of liver disease.
- •Known hepatic or biliary abnormalities.
- •Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing.
- •History of allergy or intolerance to penicillin or cephalosporin.
- •History of clinically significant allergic reaction (eg, anaphylaxis or angioedema) to any product.
- •Live vaccine(s) within 1 month prior to Screening or plans to receive such vaccines during the study.
- •Evidence of human immunodeficiency virus (HIV) infection (positive HIV type 1 or type 2 antibody).
- •Evidence of hepatitis B infection (positive hepatitis B surface antigen [HBsAg] or positive total hepatitis B core antibody [HBcAb] with negative surface antibody [anti-HBs]), or hepatitis C viral infection (positive HCV RNA).
- •Female participants who have a positive pregnancy test at Screening or Admission.
- •Positive prestudy drug/alcohol screen; positive result may be repeated once.
研究组 & 干预措施
Gefurulimab PFS-SD
Participants will be administered gefurulimab as a single dose of 600 mg by PFS-SD on the abdomen, thigh, or upper arm.
干预措施: Gefurulimab PFS-SD (Drug)
Gefurulimab AI
Participants will be administered gefurulimab as a single dose of 600 mg by AI on the abdomen, thigh, or upper arm.
干预措施: Gefurulimab AI (Drug)
结局指标
主要结局
Maximum (peak) concentration observed after study intervention administration (Cmax)
时间窗: Day 1 up to early discontinuation or Day 92
The Cmax exposure in healthy participants following a single SC dose of 600 mg gefurulimab by AI comparable to the PK exposure using the PFS-SD will be assessed.
Area under the serum concentration-time curve from time zero to the last measurable concentration (AUClast)
时间窗: Day 1 up to early discontinuation or Day 92
The AUClast exposure in healthy participants following a single SC dose of 600 mg gefurulimab by AI comparable to the PK exposure using the PFS-SD will be assessed.
Area under the serum concentration-time curve from time zero to time infinity (AUCinf)
时间窗: Day 1 up to early discontinuation or Day 92
The AUClinf exposure in healthy participants following a single SC dose of 600 mg gefurulimab by AI comparable to the PK exposure using the PFS-SD will be assessed.
次要结局
- Apparent volume of distribution (Vd/F)(Day 1 to Day 92)
- Time to maximum observed serum concentration (tmax)(Day 1 to Day 92)
- Serum free C5 (complement component 5) concentrations(Day 1 to Day 92)
- Incidence of antidrug antibody (ADA) to gefurulimab category of immune-response and titer(Day 1, Day 92)
- Terminal elimination half-life (t½)(Day 1 to Day 92)
- Number of subjects with TEAEs (treatment-emergent adverse event) and TESAEs (treatment-emergent serious adverse event)(From Admission (Day-1) to Day 92)
- Apparent total body clearance of the study intervention from serum (CL/F)(Day 1 to Day 92)
- Number of reported outcome of attempted full-dose administration via AI (autoinjector) or PFS-SD (prefilled syringe with needle safety device)(Day 1)
- Number of reported device deficiencies/complaints and associated device investigations(Day 1)