An Exploratory, Multi-Centre, Interventional, Prospective, Randomised, Double-Blind, Placebo-Controlled Clinical Trial to Assess the Safety and Efficacy of AON-D21 in Patients With Severe Community-Acquired Pneumonia.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 150
- 试验地点
- 32
- 主要终点
- Incidence of Treatment-Emergent Adverse Events.
研究概览
简要总结
The goal of this clinical trial is to compare the safety and efficacy of AON-D21 versus placebo, both on top of standard of care, in patients with severe community acquired pneumonia admitted to ICU (or similar unit). The main questions to answer are:
- The safety and tolerability of AON-D21 vs placebo.
- The efficacy of AON-D21vs placebo.
- The pharmacokinetics of AON-D21.
- The pharmacodynamics of AON D21.
- To identify biomarkers for patient stratification and analyses in future trials.
详细描述
This clinical trial will enroll 100 participants, randomized 2:1 (AON-D21:placebo).
Participants diagnosed with severe community-acquired pneumonia of bacterial or viral origin requiring admission to an intensive care unit or similar setting, will receive either AON-D21 or placebo intravenous infusions for up to 10 days.
In addition, participants will receive standard of care as per local guidelines.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Placebo-controlled
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Community-acquired pneumonia, confirmed or suspected of bacterial or viral origin.
- •Admitted to an ICU (or similar unit).
- •Requiring respiratory support by HFO ≥ 30 L/min with FiO2 ≥ 30% or NIV or IMV or ECMO.
- •CRP ≥ 50 mg/L.
- •PaO2/FiO2 ratio ≤ 150 mmHg.
- •Treatment initiation no more than 48 h after initiation of respiratory support (HFO ≥ 30 L/min with FiO2 ≥ 30%, NIV, IMV or ECMO).
- •Written informed consent.
- •Age ≥ 18 years to ≤ 85 years.
- •Body mass index ≥ 17.5 kg/m² and ≤ 40 kg/m².
- •For female participants of childbearing potential, agreement to use dual methods of contraception until Day
- •For male participants with female partners of childbearing potential, agreement to use barrier method of contraception until Day 60 and to refrain from donating sperm during the study and for 3 months after the last infusion.
排除标准
- •Refractory septic shock.
- •Not expected to survive 72 hours.
- •Hospital-acquired or ventilator-associated pneumonia or known or suspected pneumonia due to aspiration or other physical injury or trauma or tuberculosis.
- •Known or suspected hypersensitivity to AON-D21 or any components of the formulation used (e.g., PEG, mannitol or EDTA) or a history of clinically relevant allergy requiring continuous treatment, or of anaphylaxis.
- •Known fibrotic lung disease, bronchiectasis or any other known severe chronic respiratory disease.
- •Active malignant disease.
- •Factors other than a pathogen suspected or confirmed to be causative for the respiratory insufficiency.
- •Hepatocellular injury defined by an ALT or AST value ≥ 3 times the ULN. Known acute or chronic liver disease with Child-Pugh C (See Appendix 13.6.2).
- •Any medical disease or condition that, in the opinion of the investigator(s), compromises the participant's safety or compromises the interpretation of the results.
- •Receiving chronic immunosuppressive therapy in relevant doses.
- •Known immunodeficiency disease/condition.
- •Nursing and pregnant women (defined as the state after conception until the termination of gestation, screened in all women of child-bearing potential with a chorionic gonadotrophin (hCG) blood test (local laboratory).
- •Current or recent participation in an investigational trial.
- •Systemic treatment with any complement inhibitor.
- •Known complement deficiency.
- •Unlikely to remain at the investigational site beyond 96 h.
研究组 & 干预措施
AON-D21 plus Standard of Care
Sterile liquid formulation of AON-D21 in 4% mannitol + 0.05% EDTA in glass vials. It will be administered intravenously, for up to 10 days plus Standard of Care therapy for severe community-acquired pneumonia as per local guidelines.
干预措施: AON-D21 (Drug)
Placebo plus Standard of Care
Sterile liquid formulation of 5% glucose solution in matched glass vials with a 1.5 mL fill volume. It will be administered intravenously, for up to 10 days plus Standard of Care therapy for severe community-acquired pneumonia as per local guidelines.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events.
时间窗: 28 days.
To evaluate the safety and tolerability of AON-D21 versus placebo, including the frequency, severity, and relatedness to study drug of serious and non-serious treatment-emergent adverse events (TEAEs) until Day 28.
次要结局
- Volume of distribution of AON-D21.(12 days.)
- Efficacy-no longer requiring respiratory support.(28 days.)
- Cmax of AON-D21.(10 days.)
- Cav of AON-D21.(10 days.)
- Ctrough of AON-D21.(10 days.)
- Efficacy-all-cause mortality.(60 days.)
- C5a's measurement(12 days.)
- Efficacy-organ support-free days.(28 days.)
- Efficacy-time to improvement.(28 days.)
- Efficacy-respiratory support-free days.(28 days.)
- Half-life of AON-D21.(12 days.)
- Accumulation of AON-D21.(10 days.)
- Clearance of AON-D21.(12 days.)
- Efficacy-no longer requiring any organ support.(28 days.)
- Efficacy-mean change in SaO2/FiO2 ratio.(7 days.)
- AUC of AON-D21.(10 days.)
- Tmax of AON-D21.(10 days.)
- Efficacy-invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO)-free days.(28 days.)
- Procalcitonin's measurement.(12 days.)
- C5a inhibition with AON-D21.(12 days.)
- Ferritin's measurement.(12 days.)
- sC5b-9's measurement.(12 days.)
- IL-6's measurement.(12 days.)
- Neutrophil elastase's measurement.(12 days.)
- D-dimer's measurement.(12 days.)
- Pro-Adrenomedullin's measurement.(12 days.)
- Efficacy-all-cause mortality.(28 days.)