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
| Arm | Description | Assigned 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. |
|
|
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. |
|
Recruiting Locations
University of Alabama at Birmingham Heersink School of Medicine
Birmingham 4049979, Alabama 4829764 35233
Birmingham 4049979, Alabama 4829764 35233
Contact:
Derek Russell, MD
Derek Russell, MD
More Details
- Status
- Recruiting
- Sponsor
- Aptarion Biotech AG
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.