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

Purpose

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.

Condition

  • Community-acquired Pneumonia

Eligibility

Eligible Ages
Between 18 Years and 85 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Multi-center, interventional, randomized, double-blind, placebo-controlled study.
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Placebo-controlled

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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.
  • 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 Comparator
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.
  • Drug: Placebo
    Sterile liquid formulation of 5% glucose solution in matched glass vials with a 1.5 mL fill volume.

Recruiting Locations

University of Alabama at Birmingham Heersink School of Medicine
Birmingham 4049979, Alabama 4829764 35233
Contact:
Derek Russell, MD

More Details

Status
Recruiting
Sponsor
Aptarion Biotech AG

Study Contact

Antonio Perez, MD
+49-30-959 982-140
perez@aptarion.com

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.