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

NCT05962606 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: S-D21-C300
• Study Type: interventional
• Target: 150
• Locations: 6 countries
• Sites: 27

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.

Conditions

Community-acquired Pneumonia

Keywords

Pneumonia; Community-acquired; Severe; Bacterial; Viral

Outcome Measures

Primary Outcomes (1)

• 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.

  28 days.

Secondary Outcomes (27)

• Efficacy-no longer requiring respiratory support.

  28 days.

• Efficacy-no longer requiring any organ support.

  28 days.

• Efficacy-time to improvement.

  28 days.

• Efficacy-mean change in SaO2/FiO2 ratio.

  7 days.

• Efficacy-organ support-free days.

  28 days.

Study Arms (2)

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.

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.

Drug: Placebo

Interventions

AON-D21 DRUG

AON-D21 is a Pegylated L-configured aptamer that binds and thereby neutralizes the complement component C5a from activating both C5a receptors.

AON-D21 plus Standard of Care

Placebo DRUG

Sterile liquid formulation of 5% glucose solution in matched glass vials with a 1.5 mL fill volume.

Placebo plus Standard of Care

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Aptarion Biotech AG: lead

Study Sites (27)

University of Alabama at Birmingham Heersink School of Medicine

Birmingham, Alabama, 35233, United States

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

Clinique Saint Pierre

Ottignies, Belgium

Location

Centre Hospitalier Argenteuil

Argenteuil, France

Location

Centre Hospitalier Départemental Vendée

La Roche-sur-Yon, France

Location

CHU Dupuytren

Limoges, France

Location

Centre Hospitalier de Melun

Melun, France

Location

Hotel Dieu - CHU Nantes

Nantes, France

Location

Assistance Publique-Hopitaux de Paris (AP-HP)

Paris, France

Location

Nouvel Hôpital Civil

Strasbourg, France

Location

CHRU de Tours Hôpital Bretonneau

Tours, France

Location

Hôpital Nord Franche Comté

Trévenans, France

Location

Charité - Universitätsmedizin Berlin

Berlin, Germany

Location

Cologne-Merheim Hospital Lung Clinic

Cologne, Germany

Location

Universitaetsklinikum Giessen und Marburg GmbH

Giessen, Germany

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital Doctor Josep Trueta

Girona, Spain

Location

Hospital Clinico San Carlos

Madrid, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, Spain

Location

University Hospital Bristol and Weston NHS

Bristol, United Kingdom

Location

University Hospital of Wales

Cardiff, United Kingdom

Location

Liverpool University Hospitals NHS Foundation Trust

Liverpool, United Kingdom

Location

University College London

London, United Kingdom

Location

University Hospitals Plymouth NHS Trust, Derriford Hospital

Plymouth, United Kingdom

Location

Royal Berkshire Foundation Trust

Reading, United Kingdom

Location

Mid Yokshire Teaching NHS Trust

Wakefield, United Kingdom

Location

York Hospital

York, United Kingdom

Location

MeSH Terms

Conditions

Community-Acquired Pneumonia; Pneumonia; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Martin Witzenrath, MD

  Critical Care Medicine. Charité Universitätsmedizin Berlin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo-controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multi-center, interventional, randomized, double-blind, placebo-controlled study.

Study Record Dates

• First Submitted: July 17, 2023
• First Posted: July 27, 2023
• Study Start: February 2, 2024
• Primary Completion: March 16, 2026
• Study Completion: March 16, 2026
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); DE (3); FR (9); ES (4); GB (8); BE (2)