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

NCT ID: NCT05962606

Last Updated: 2025-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-02

Study Completion Date

2026-06-30

Brief Summary

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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

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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

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Community-acquired Pneumonia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Multi-center, interventional, randomized, double-blind, placebo-controlled study.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Placebo-controlled

Study Groups

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AON-D21 plus Standard of Care

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.

Group Type EXPERIMENTAL

AON-D21

Intervention Type DRUG

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

Placebo plus Standard of Care

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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AON-D21

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Aptarion Biotech AG

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Martin Witzenrath, MD

Role: PRINCIPAL_INVESTIGATOR

Critical Care Medicine. Charité Universitätsmedizin Berlin

Locations

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University of Alabama at Birmingham Heersink School of Medicine

Birmingham, Alabama, United States

Site Status RECRUITING

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status RECRUITING

Clinique Saint Pierre

Ottignies, , Belgium

Site Status RECRUITING

Centre Hospitalier Argenteuil

Argenteuil, , France

Site Status RECRUITING

Centre Hospitalier Départemental Vendée

La Roche-sur-Yon, , France

Site Status RECRUITING

CHU Dupuytren

Limoges, , France

Site Status RECRUITING

Centre Hospitalier de Melun

Melun, , France

Site Status RECRUITING

Hotel Dieu - CHU Nantes

Nantes, , France

Site Status RECRUITING

Assistance Publique-Hopitaux de Paris (AP-HP)

Paris, , France

Site Status RECRUITING

Nouvel Hôpital Civil

Strasbourg, , France

Site Status RECRUITING

CHRU de Tours Hôpital Bretonneau

Tours, , France

Site Status RECRUITING

Hôpital Nord Franche Comté

Trévenans, , France

Site Status RECRUITING

Charité - Universitätsmedizin Berlin

Berlin, , Germany

Site Status RECRUITING

Cologne-Merheim Hospital Lung Clinic

Cologne, , Germany

Site Status RECRUITING

University Hospital Cologne

Cologne, , Germany

Site Status WITHDRAWN

Universitaetsklinikum Giessen und Marburg GmbH

Giessen, , Germany

Site Status RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status RECRUITING

Hospital Doctor Josep Trueta

Girona, , Spain

Site Status RECRUITING

Hospital Clinico San Carlos

Madrid, , Spain

Site Status RECRUITING

Hospital Universitari Mútua Terrassa

Terrassa, , Spain

Site Status WITHDRAWN

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

Site Status RECRUITING

University Hospital Bristol and Weston NHS

Bristol, , United Kingdom

Site Status RECRUITING

University Hospital of Wales

Cardiff, , United Kingdom

Site Status RECRUITING

Liverpool University Hospitals NHS Foundation Trust

Liverpool, , United Kingdom

Site Status RECRUITING

University College London

London, , United Kingdom

Site Status RECRUITING

University Hospitals Plymouth NHS Trust, Derriford Hospital

Plymouth, , United Kingdom

Site Status RECRUITING

Royal Berkshire Foundation Trust

Reading, , United Kingdom

Site Status RECRUITING

Mid Yokshire Teaching NHS Trust

Wakefield, , United Kingdom

Site Status RECRUITING

York Hospital

York, , United Kingdom

Site Status RECRUITING

Countries

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United States Belgium France Germany Spain United Kingdom

Central Contacts

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Antonio Perez, MD

Role: CONTACT

+49-30-959 982-140

Axel Vater, PhD

Role: CONTACT

+49-30-959 982-140

Facility Contacts

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Derek Russell, MD

Role: primary

Xavier Wittebole, Prof.

Role: primary

Nicolas De Schryver, Dr.

Role: primary

Gaetan Plantefeve, Dr.

Role: primary

Jean-Claude Lacherade, Dr.

Role: primary

Bruno Francois, Dr.

Role: primary

Mehran Monchi, Dr.

Role: primary

Gauthier Blonz, Dr.

Role: primary

Jean-Damien Ricard, Prof.

Role: primary

Ferhat Meziani, Prof.

Role: primary

Emmanuelle Mercier, Dr.

Role: primary

Julio Badie, Dr.

Role: primary

Martin Witzenrath, Prof.

Role: primary

Christian Karagiannidis, Dr.

Role: primary

Istvan Vadasz, Prof.

Role: primary

Ricard Ferrer, Dr.

Role: primary

Carolina Lorencio, Dr.

Role: primary

Miguel Sanchez-Garcia, Dr.

Role: primary

Paula Ramirez, Dr.

Role: primary

Matt Wise, Prof.

Role: primary

Ingeborg Welters, Prof.

Role: primary

David Brealey, Dr.

Role: primary

Robert Jackson, Dr

Role: primary

Matthew Frise, Dr.

Role: primary

Brendan Sloan, Dr.

Role: primary

Joseph Carter, Dr.

Role: primary

Other Identifiers

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S-D21-C300

Identifier Type: -

Identifier Source: org_study_id