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

Aptarion Biotech

Status and phase: Enrolling; Phase 2

Conditions: Community-acquired Pneumonia

Treatments: Drug: AON-D21; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05962606

S-D21-C300

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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100 participants in 2 patient groups, including a placebo group

AON-D21 plus Standard of Care

Experimental group

Description:

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.

Treatment:

Drug: AON-D21

Placebo plus Standard of Care

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo