Safety and Efficacy of AON-D21 in Severe Community-Acquired Pneumonia.
- Registration Number
- NCT05962606
- Lead Sponsor
- Aptarion Biotech AG
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 150
- 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 60.
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AON-D21 plus Standard of Care AON-D21 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. Placebo plus Standard of Care Placebo 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.
- Primary Outcome Measures
Name Time Method Incidence of Treatment-Emergent Adverse Events. 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.
- Secondary Outcome Measures
Name Time Method Volume of distribution of AON-D21. 12 days. Volume of distribution (Vz).
Efficacy-no longer requiring respiratory support. 28 days. Comparing AON-D21 vs placebo on time to no longer requiring respiratory support (defined as high-flow oxygen (HFO) ≥ 30 L/min with FiO2 ≥ 30%), non-invasive mechanical ventilation (NIV), invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) within 28 days.
Cmax of AON-D21. 10 days. Maximum concentration at steady state (Cmax)
Cav of AON-D21. 10 days. Average drug concentration at steady state (Cav).
Ctrough of AON-D21. 10 days. Trough concentrations (Ctrough).
Efficacy-all-cause mortality. 60 days. Comparing AON-D21 vs placebo on all-cause mortality up to Day 60.
C5a's measurement 12 days. Evolution of C5a over time.
Efficacy-no longer requiring any organ support. 28 days. Comparing AON-D21 vs placebo on time no longer requiring any organ support within 28 days.
Efficacy-time to improvement. 28 days. Comparing AON-D21 vs placebo on time to improvement (defined as a de-escalation in respiratory support) within 28 days.
Efficacy-organ support-free days. 28 days. Comparing AON-D21 vs placebo on organ support-free days until Day 28.
Efficacy-respiratory support-free days. 28 days. Comparing AON-D21 vs placebo on respiratory support-free days until Day 28.
Half-life of AON-D21. 12 days. Terminal half-life at steady state (t1/2).
Accumulation of AON-D21. 10 days. Accumulation ratio for Cmax.
Clearance of AON-D21. 12 days. Clearance (CL).
Efficacy-mean change in SaO2/FiO2 ratio. 7 days. Comparing AON-D21 vs placebo on mean change in SaO2/FiO2 ratio from Day 1 (Baseline) to Day 7.
AUC of AON-D21. 10 days. Area under the concentration-time curve (AUC) over the dosing interval at steady state (AUC0-tau).
Tmax of AON-D21. 10 days. Time of maximum concentration at steady state (Tmax).
Efficacy-invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO)-free days. 28 days. Comparing AON-D21 vs placebo on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO)-free days until Day 28.
Procalcitonin's measurement. 12 days. Evolution of procalcitonin over time.
C5a inhibition with AON-D21. 12 days. To determine the C5a inhibition capacity of AON-D21 by measuring active C5a in blood using a cell-based assay.
Ferritin's measurement. 12 days. Evolution of ferritin over time.
sC5b-9's measurement. 12 days. Evolution of sC5b-9 over time.
IL-6's measurement. 12 days. Evolution of IL-6 over time.
Neutrophil elastase's measurement. 12 days. Evolution of neutrophil elastase over time.
D-dimer's measurement. 12 days. Evolution of D-dimer over time.
Pro-Adrenomedullin's measurement. 12 days. Evolution of Pro-Adrenomedullin over time.
Trial Locations
- Locations (28)
University Hospital Cologne
🇩🇪Cologne, Germany
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
Clinique Saint Pierre
🇧🇪Ottignies, Belgium
Centre Hospitalier Argenteuil
🇫🇷Argenteuil, France
Centre Hospitalier Départemental Vendée
🇫🇷La Roche-sur-Yon, France
CHU Dupuytren
🇫🇷Limoges, France
Centre Hospitalier de Melun
🇫🇷Melun, France
Hotel Dieu - CHU Nantes
🇫🇷Nantes, France
Assistance Publique-Hopitaux de Paris (AP-HP)
🇫🇷Paris, France
Nouvel Hôpital Civil
🇫🇷Strasbourg, France
CHRU de Tours Hôpital Bretonneau
🇫🇷Tours, France
Hôpital Nord Franche Comté
🇫🇷Trévenans, France
Charité - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Cologne-Merheim Hospital Lung Clinic
🇩🇪Cologne, Germany
Universitaetsklinikum Giessen und Marburg GmbH
🇩🇪Gießen, Germany
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Doctor Josep Trueta
🇪🇸Girona, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitari Mútua Terrassa
🇪🇸Terrassa, Spain
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸Valencia, Spain
University Hospital Bristol and Weston NHS
🇬🇧Bristol, United Kingdom
University Hospital of Wales
🇬🇧Cardiff, United Kingdom
Liverpool University Hospitals NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
University College London
🇬🇧London, United Kingdom
University Hospitals Plymouth NHS Trust, Derriford Hospital
🇬🇧Plymouth, United Kingdom
Royal Berkshire Foundation Trust
🇬🇧Reading, United Kingdom
Mid Yokshire Teaching NHS Trust
🇬🇧Wakefield, United Kingdom
York Hospital
🇬🇧York, United Kingdom