Safety and Efficacy of AON-D21 in Severe Community-Acquired Pneumonia.

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.

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.