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

Community-acquired Pneumonia Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05962606
• Other study ID #: S-D21-C300
• Status: Recruiting
• Phase: Phase 2
• Start date: February 2, 2024
• Est. completion date: June 30, 2025

Study information

• Verified date: June 2024
• Source: Aptarion Biotech AG
• Contact: Antonio Perez, MD
• Phone: +49-30-959 982-140
• Email: perez[@]aptarion.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

• 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 30, 2025
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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 = 300 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.

Related Conditions & MeSH terms

• Community-acquired Pneumonia
• Pneumonia

Intervention

Drug:
• AON-D21
AON-D21 is a Pegylated L-configured aptamer that binds and thereby neutralizes the complement component C5a from activating both C5a receptors.
• Placebo
Sterile liquid formulation of 5% glucose solution in matched glass vials with a 1.5 mL fill volume.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Clinique Saint Pierre	Ottignies
France	Centre Hospitalier Argenteuil	Argenteuil
France	Centre Hospitalier Départemental Vendée	La Roche-sur-Yon
France	CHU Dupuytren	Limoges
France	Centre Hospitalier de Melun	Melun
France	Hotel Dieu - CHU Nantes	Nantes
France	Assistance Publique-Hopitaux de Paris (AP-HP)	Paris
France	Nouvel Hôpital Civil	Strasbourg
France	CHRU de Tours Hôpital Bretonneau	Tours
France	Hôpital Nord Franche Comté	Trévenans
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Cologne-Merheim Hospital Lung Clinic	Cologne
Germany	Universitaetsklinikum Giessen und Marburg GmbH	Gießen
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitari Mútua Terrassa	Terrassa
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Liverpool University Hospitals NHS Foundation Trust	Liverpool
United Kingdom	University College London	London
United Kingdom	Royal Berkshire Foundation Trust	Reading
United Kingdom	Mid Yokshire Teaching NHS Trust	Wakefield

Sponsors (1)

Lead Sponsor	Collaborator
Aptarion Biotech AG

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	28 days.
Secondary	Efficacy-no longer requiring any organ support.	Comparing AON-D21 vs placebo on time no longer requiring any organ support within 28 days.	28 days.
Secondary	Efficacy-time to improvement.	Comparing AON-D21 vs placebo on time to improvement (defined as a de-escalation in respiratory support) within 28 days.	28 days.
Secondary	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.	7 days.
Secondary	Efficacy-organ support-free days.	Comparing AON-D21 vs placebo on organ support-free days until Day 28.	28 days.
Secondary	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.	28 days.
Secondary	Efficacy-respiratory support-free days.	Comparing AON-D21 vs placebo on respiratory support-free days until Day 28.	28 days.
Secondary	Efficacy-all-cause mortality.	Comparing AON-D21 vs placebo on all-cause mortality up to Day 28.	28 days.
Secondary	Efficacy-all-cause mortality.	Comparing AON-D21 vs placebo on all-cause mortality up to Day 60.	60 days.
Secondary	AUC of AON-D21.	Area under the concentration-time curve (AUC) over the dosing interval at steady state (AUC0-tau).	10 days.
Secondary	Cmax of AON-D21.	Maximum concentration at steady state (Cmax)	10 days.
Secondary	Cav of AON-D21.	Average drug concentration at steady state (Cav).	10 days.
Secondary	Ctrough of AON-D21.	Trough concentrations (Ctrough).	10 days.
Secondary	Tmax of AON-D21.	Time of maximum concentration at steady state (Tmax).	10 days.
Secondary	Half-life of AON-D21.	Terminal half-life at steady state (t1/2).	12 days.
Secondary	Accumulation of AON-D21.	Accumulation ratio for Cmax.	10 days.
Secondary	Clearance of AON-D21.	Clearance (CL).	12 days.
Secondary	Volume of distribution of AON-D21.	Volume of distribution (Vz).	12 days.
Secondary	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.	12 days.
Secondary	Procalcitonin's measurement.	Evolution of procalcitonin over time.	12 days.
Secondary	Ferritin's measurement.	Evolution of ferritin over time.	12 days.
Secondary	IL-6's measurement.	Evolution of IL-6 over time.	12 days.
Secondary	C5a's measurement	Evolution of C5a over time.	12 days.
Secondary	sC5b-9's measurement.	Evolution of sC5b-9 over time.	12 days.
Secondary	Neutrophil elastase's measurement.	Evolution of neutrophil elastase over time.	12 days.
Secondary	D-dimer's measurement.	Evolution of D-dimer over time.	12 days.
Secondary	Pro-Adrenomedullin's measurement.	Evolution of Pro-Adrenomedullin over time.	12 days.