Clinical trial NCT05962606: Safety and Efficacy of AON-D21 in Severe Community-Acquired Pneumonia.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Community-acquired Pneumonia
Keywords: Pneumonia
Community-acquired
Severe
Bacterial
Viral
Lead sponsor: Aptarion Biotech AG
Sponsor class: INDUSTRY
First posted: 2023-07-27
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-center, interventional, randomized, double-blind, placebo-controlled study.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events.
timeFrame: 28 days.
Secondary outcomes:
measure: Efficacy-no longer requiring respiratory support.
timeFrame: 28 days.
measure: Efficacy-no longer requiring any organ support.
timeFrame: 28 days.
measure: Efficacy-time to improvement.
timeFrame: 28 days.
measure: Efficacy-mean change in SaO2/FiO2 ratio.
timeFrame: 7 days.
measure: Efficacy-organ support-free days.
timeFrame: 28 days.
measure: Efficacy-invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO)-free days.
timeFrame: 28 days.
measure: Efficacy-respiratory support-free days.
timeFrame: 28 days.
measure: Efficacy-all-cause mortality.
timeFrame: 28 days.
measure: Efficacy-all-cause mortality.
timeFrame: 60 days.
measure: AUC of AON-D21.
timeFrame: 10 days.
measure: Cmax of AON-D21.
timeFrame: 10 days.
measure: Cav of AON-D21.
timeFrame: 10 days.
measure: Ctrough of AON-D21.
timeFrame: 10 days.
measure: Tmax of AON-D21.
timeFrame: 10 days.
measure: Half-life of AON-D21.
timeFrame: 12 days.
measure: Accumulation of AON-D21.
timeFrame: 10 days.
measure: Clearance of AON-D21.
timeFrame: 12 days.
measure: Volume of distribution of AON-D21.
timeFrame: 12 days.
measure: C5a inhibition with AON-D21.
timeFrame: 12 days.
measure: Procalcitonin's measurement.
timeFrame: 12 days.
measure: Ferritin's measurement.
timeFrame: 12 days.
measure: IL-6's measurement.
timeFrame: 12 days.
measure: C5a's measurement
timeFrame: 12 days.
measure: sC5b-9's measurement.
timeFrame: 12 days.
measure: Neutrophil elastase's measurement.
timeFrame: 12 days.
measure: D-dimer's measurement.
timeFrame: 12 days.
measure: Pro-Adrenomedullin's measurement.
timeFrame: 12 days.
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Ottignies
country: Belgium
facility: Clinique Saint Pierre
city: Argenteuil
country: France
facility: Centre Hospitalier Argenteuil
city: La Roche-sur-Yon
country: France
facility: Centre Hospitalier Départemental Vendée
city: Limoges
country: France
facility: CHU Dupuytren
city: Melun
country: France
facility: Centre Hospitalier de Melun
city: Nantes
country: France
facility: Hotel Dieu - CHU Nantes
city: Paris
country: France
facility: Assistance Publique-Hopitaux de Paris (AP-HP)
city: Strasbourg
country: France
facility: Nouvel Hôpital Civil
city: Tours
country: France
facility: CHRU de Tours Hôpital Bretonneau
city: Trévenans
country: France
facility: Hôpital Nord Franche Comté
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Cologne
country: Germany
facility: Cologne-Merheim Hospital Lung Clinic
city: Cologne
country: Germany
facility: University Hospital Cologne
city: Gießen
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Girona
country: Spain
facility: Hospital Doctor Josep Trueta
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Terrassa
country: Spain
facility: Hospital Universitari Mútua Terrassa
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Bristol
country: United Kingdom
facility: University Hospital Bristol and Weston NHS
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Liverpool
country: United Kingdom
facility: Liverpool University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth NHS Trust, Derriford Hospital
city: Reading
country: United Kingdom
facility: Royal Berkshire Foundation Trust
city: Wakefield
country: United Kingdom
facility: Mid Yokshire Teaching NHS Trust
city: York
country: United Kingdom
facility: York Hospital
Study officials:
affiliation: Critical Care Medicine. Charité Universitätsmedizin Berlin
name: Martin Witzenrath, MD
role: PRINCIPAL_INVESTIGATOR
References: