Community-acquired PneumoniaPhase 2NCT05962606
Safety and Efficacy of AON-D21 in Severe Community-Acquired Pneumonia.
A Phase 2 study testing AON-D21 in people with Community-acquired Pneumonia, run by Aptarion Biotech AG at 27 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Community-acquired Pneumonia
- What is being tested?
- AON-D21
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 27 sitesin 6 countries
- Study dates
- 2 Feb 2024to 16 Mar 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
27 sites in 6 countries.
27 sites in 6 countries
France9 sites
Centre Hospitalier Argenteuil
Argenteuil
Centre Hospitalier Départemental Vendée
La Roche-sur-Yon
CHU Dupuytren
Limoges
Centre Hospitalier de Melun
Melun
Hotel Dieu - CHU Nantes
Nantes
Assistance Publique-Hopitaux de Paris (AP-HP)
Paris
Nouvel Hôpital Civil
Strasbourg
CHRU de Tours Hôpital Bretonneau
Tours
Hôpital Nord Franche Comté
Trévenans
United Kingdom8 sites
University Hospital Bristol and Weston NHS
Bristol
University Hospital of Wales
Cardiff
Liverpool University Hospitals NHS Foundation Trust
Liverpool
University College London
London
University Hospitals Plymouth NHS Trust, Derriford Hospital
Plymouth
Royal Berkshire Foundation Trust
Reading
Mid Yokshire Teaching NHS Trust
Wakefield
York Hospital
York
Spain4 sites
Hospital Universitari Vall d'Hebron
Barcelona
Hospital Doctor Josep Trueta
Girona
Hospital Clinico San Carlos
Madrid
Hospital Universitari i Politecnic La Fe de Valencia
Valencia
Germany3 sites
Charité - Universitätsmedizin Berlin
Berlin
Cologne-Merheim Hospital Lung Clinic
Cologne
Universitaetsklinikum Giessen und Marburg GmbH
Giessen
Belgium2 sites
Cliniques Universitaires Saint-Luc
Brussels
Clinique Saint Pierre
Ottignies
United States1 site
University of Alabama at Birmingham Heersink School of Medicine
Birmingham, Alabama, 35233
About this study
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.
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.
Read the 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.
- Conditions
- Community-acquired Pneumonia
- Being tested
- AON-D21, Placebo
- Keywords
- Pneumonia, Community-acquired, Severe, Bacterial, Viral
- Medical subject headings
- Community-Acquired Pneumonia, Pneumonia, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AON-D21Drug
AON-D21 is a Pegylated L-configured aptamer that binds and thereby neutralizes the complement component C5a from activating both C5a receptors.
PlaceboDrug
Sterile liquid formulation of 5% glucose solution in matched glass vials with a 1.5 mL fill volume.
| Study group | Role | What they receive |
|---|---|---|
| AON-D21 plus Standard of Care | Experimental | 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. Receives: Drug: AON-D21 |
| Placebo plus Standard of Care | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events.
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.
Measured: 28 days.
Secondary outcomes (27)
Efficacy-no longer requiring respiratory support.
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.
Measured: 28 days.
Efficacy-no longer requiring any organ support.
Comparing AON-D21 vs placebo on time no longer requiring any organ support within 28 days.
Measured: 28 days.
Efficacy-time to improvement.
Comparing AON-D21 vs placebo on time to improvement (defined as a de-escalation in respiratory support) within 28 days.
Measured: 28 days.
Efficacy-mean change in SaO2/FiO2 ratio.
Comparing AON-D21 vs placebo on mean change in SaO2/FiO2 ratio from Day 1 (Baseline) to Day 7.
Measured: 7 days.
Efficacy-organ support-free days.
Comparing AON-D21 vs placebo on organ support-free days until Day 28.
Measured: 28 days.
Efficacy-invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO)-free days.
Comparing AON-D21 vs placebo on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO)-free days until Day 28.
Measured: 28 days.
Efficacy-respiratory support-free days.
Comparing AON-D21 vs placebo on respiratory support-free days until Day 28.
Measured: 28 days.
Efficacy-all-cause mortality.
Comparing AON-D21 vs placebo on all-cause mortality up to Day 28.
Measured: 28 days.
Efficacy-all-cause mortality.
Comparing AON-D21 vs placebo on all-cause mortality up to Day 60.
Measured: 60 days.
AUC of AON-D21.
Area under the concentration-time curve (AUC) over the dosing interval at steady state (AUC0-tau).
Measured: 10 days.
Cmax of AON-D21.
Maximum concentration at steady state (Cmax)
Measured: 10 days.
Cav of AON-D21.
Average drug concentration at steady state (Cav).
Measured: 10 days.
Ctrough of AON-D21.
Trough concentrations (Ctrough).
Measured: 10 days.
Tmax of AON-D21.
Time of maximum concentration at steady state (Tmax).
Measured: 10 days.
Half-life of AON-D21.
Terminal half-life at steady state (t1/2).
Measured: 12 days.
Accumulation of AON-D21.
Accumulation ratio for Cmax.
Measured: 10 days.
Clearance of AON-D21.
Clearance (CL).
Measured: 12 days.
Volume of distribution of AON-D21.
Volume of distribution (Vz).
Measured: 12 days.
C5a inhibition with AON-D21.
To determine the C5a inhibition capacity of AON-D21 by measuring active C5a in blood using a cell-based assay.
Measured: 12 days.
Procalcitonin's measurement.
Evolution of procalcitonin over time.
Measured: 12 days.
Ferritin's measurement.
Evolution of ferritin over time.
Measured: 12 days.
IL-6's measurement.
Evolution of IL-6 over time.
Measured: 12 days.
C5a's measurement
Evolution of C5a over time.
Measured: 12 days.
sC5b-9's measurement.
Evolution of sC5b-9 over time.
Measured: 12 days.
Neutrophil elastase's measurement.
Evolution of neutrophil elastase over time.
Measured: 12 days.
D-dimer's measurement.
Evolution of D-dimer over time.
Measured: 12 days.
Pro-Adrenomedullin's measurement.
Evolution of Pro-Adrenomedullin over time.
Measured: 12 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2023
- Study start2 Feb 2024
- Primary completion16 Mar 2026
- Study completion16 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Community-acquired PneumoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multi-center, interventional, randomized, double-blind, placebo-controlled study.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aptarion Biotech AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Martin Witzenrath, MD, Principal investigator, Critical Care Medicine. Charité Universitätsmedizin Berlin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05962606
- Sponsor's protocol ID
- S-D21-C300
- Status last verified
- Mar 2026
- First submitted
- 17 Jul 2023
- Last updated
- 18 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT05962606
- Acronym / sponsor ID
- S-D21-C300
- Conditions
- Community-acquired Pneumonia
- Keywords
- Pneumonia, Community-acquired, Severe, Bacterial, Viral
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Aptarion Biotech AGIndustry (pharma, biotech, devices)
- Study start
- 2 Feb 2024 (actual)
- Primary completion
- 16 Mar 2026 (actual)
- Study completion
- 16 Mar 2026 (actual)
- First posted
- 27 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Multi-center, interventional, randomized, double-blind, placebo-controlled study.
| Arm | Type | Receives |
|---|---|---|
| AON-D21 plus Standard of Care | Experimental | Drug: AON-D21Sterile 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 comparator | Drug: PlaceboSterile 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AON-D21AON-D21 is a Pegylated L-configured aptamer that binds and thereby neutralizes the complement component C5a from activating both C5a receptors. | Drug | AON-D21 plus Standard of Care |
| PlaceboSterile liquid formulation of 5% glucose solution in matched glass vials with a 1.5 mL fill volume. | Drug | Placebo plus Standard of Care |
Primary outcome
Incidence of Treatment-Emergent Adverse Events.
Time frame: 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.
27 secondary outcomes
Efficacy-no longer requiring respiratory support.
Time frame: 28 days.
Efficacy-no longer requiring any organ support.
Time frame: 28 days.
Efficacy-time to improvement.
Time frame: 28 days.
Efficacy-mean change in SaO2/FiO2 ratio.
Time frame: 7 days.
Efficacy-organ support-free days.
Time frame: 28 days.
Efficacy-invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO)-free days.
Time frame: 28 days.
Efficacy-respiratory support-free days.
Time frame: 28 days.
Efficacy-all-cause mortality.
Time frame: 28 days.
Efficacy-all-cause mortality.
Time frame: 60 days.
AUC of AON-D21.
Time frame: 10 days.
Cmax of AON-D21.
Time frame: 10 days.
Cav of AON-D21.
Time frame: 10 days.
Ctrough of AON-D21.
Time frame: 10 days.
Tmax of AON-D21.
Time frame: 10 days.
Half-life of AON-D21.
Time frame: 12 days.
Accumulation of AON-D21.
Time frame: 10 days.
Clearance of AON-D21.
Time frame: 12 days.
Volume of distribution of AON-D21.
Time frame: 12 days.
C5a inhibition with AON-D21.
Time frame: 12 days.
Procalcitonin's measurement.
Time frame: 12 days.
Ferritin's measurement.
Time frame: 12 days.
IL-6's measurement.
Time frame: 12 days.
C5a's measurement
Time frame: 12 days.
sC5b-9's measurement.
Time frame: 12 days.
Neutrophil elastase's measurement.
Time frame: 12 days.
D-dimer's measurement.
Time frame: 12 days.
Pro-Adrenomedullin's measurement.
Time frame: 12 days.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Witzenrath, MD principal investigator
Critical Care Medicine. Charité Universitätsmedizin Berlin
27 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AON-D21 in people with Community-acquired Pneumonia, run by Aptarion Biotech AG at 27 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in France, United Kingdom, Spain, Germany, Belgium and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events. (time frame: 28 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2026.