A Phase 1b, Randomized, Double-blind, Single and Repeat Dosing Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Lanadelumab When Added to Standard-of-Care in Subjects Hospitalized With COVID-19 Pneumonia
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- Shire
- 主要终点
- Number of Participants with Treatment emergent adverse events (TEAEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, pharmacokinetic and pharmacodynamics of lanadelumab administered by intravenous (IV) infusion when added to standard-of-care (SoC) in adults hospitalized with COVID-19 pneumonia.
详细描述
This study consists of two cohorts (Cohort 1 [Single-dose Cohort], and Cohort 2 [Repeat-dose Cohort]). Up to approximately 24 participants will be enrolled in this study, in which up to 12 participants may be enrolled into Cohort 1. However, Cohort 1 will be closed upon implementation of Amendment 2. Approximately 12 participants will be enrolled in Cohort 2. Participants will be randomized in 3:1 ratio (9 lanadelumab: 3 placebo) in each Cohort.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females 18 years of age or older at the time of signing of the informed consent form (ICF).
- •Hospitalized with evidence of COVID-19 pneumonia defined as:
- •Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection documented with polymerase chain reaction (PCR) of any specimen; e.g. respiratory, blood, urine, stool, other body fluid
- •Presence of respiratory distress as indicated by peripheral capillary oxygen saturation (SpO2) lesser than or equal to (=<) 93 percent (%) on room air or respiratory rate greater than or equal to (>=) 30 breaths per minute (breaths/min).
- •The participant (or a legally acceptable representative) has provided written informed consent approved by the institutional review board (IRB)/ independent ethics committee (IEC) before any study-specific procedures are performed.
- •Agree to adhere to the protocol-defined schedule of treatments, assessments, and procedures.
排除标准
- •Invasive mechanical ventilation (IMV) extracorporeal membrane oxygenation (ECMO) or with evidence of severe respiratory distress such that IMV/ECMO is imminent within 12 hours of randomization.
- •Where, in the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments.
- •Requiring vasopressor support (use of fluid support is not exclusionary)
- •Known or suspected venous thromboembolism.
- •Known or suspected hypersensitivity to lanadelumab or any of its excipients.
- •Dosing with an investigational drug or exposure to an investigational device within 4 weeks prior to screening.
- •Previous (within 3 months of screening) or current use of immunomodulators (e.g. methotrexate, azathioprine, 6-mercaptopurine, tumor necrosis factor [TNF] alpha inhibitor, Janus kinase [JAK] inhibitor, alpha-integrin).
- •Previous (within 3 months of screening) or current use of plasma kallikrein inhibitor or bradykinin receptor blocker.
- •Use of supplemental oxygen for a medical condition prior to receiving COVID-19 diagnosis.
- •Previously diagnosed with acquired immunodeficiency syndrome (AIDS).
- •Active tuberculosis or clinical suspicion of latent tuberculosis.
- •Any of the following laboratory abnormalities at screening:
- •Hemoglobin <= 8 grams per deciliter (g/dL)
- •White blood cells <= 3000/ microliters (μL)
- •Platelets <= 75,000/μL
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >= 3×upper limit of normal (ULN); alkaline phosphatase (ALP) >= 3×ULN; or total bilirubin greater than (>) 2×ULN (unless the bilirubin elevation is a result of Gilbert's syndrome)
- •Creatinine >= 2×ULN
- •Pregnant or breastfeeding.
- •Any significant condition (any surgical or medical condition) that, in the opinion of the investigator or sponsor, may compromise their safety or compliance, preclude the successful conduct of the study, or interfere with interpretation of the results (e.g. significant pre-existing illness or other major comorbidities that the investigator considers may confound the interpretation of study results).
研究组 & 干预措施
Lanadelumab
Participants receive 300 milligram (mg) of lanadelumab intravenous (IV) infusion on Day 1 during Cohort 1 (single dose cohort) and on Day 1 and Day 4 during Cohort 2 (repeat-dose cohort).
干预措施: Lanadelumab (Drug)
Placebo
Participants will receive placebo matching IV infusion on Day 1 during Cohort 1 (single dose cohort) and on Day 1 and Day 4 during Cohort 2 (repeat-dose cohort).
干预措施: Placebo (Other)
结局指标
主要结局
Number of Participants with Treatment emergent adverse events (TEAEs)
时间窗: From start of study drug administration to follow-up (up to Day 29)
Treatment-emergent adverse events are defined as Adverse events (AEs) with onset at the time of or following the start of treatment with study medication, or medical conditions present prior to the start of treatment but increasing in severity or relationship at the time of or following the start of treatment. SAE is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose: results in death, is lifethreatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI will include hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. Number of participants with TEAEs including AESI and SAE will be assessed.
次要结局
- Percentage Change from Baseline in Plasma Kallikrein Activity (pKal)(Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose)
- Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab(Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 1, 24, 72, 73, 144, 216, 336 hours post-dose)
- Percentage Change from Baseline in Functional C1-Inhibitor (C1-INH)(Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose)
- Percentage Change from Baseline in Cleaved High Molecular Weight Kininogen (cHMWK)(Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose)