IC14 (anti-CD14) treatment for hospitalized patients with ARDS

Phase 2, Randomized, Double-Blind, Placebo-Controlled, Safety and Efficacy Study of Anti-CD14 Treatment With a Recombinant Chimeric Monoclonal Antibody (IC14) in Hospitalized Patients With Acute Respiratory Distress Syndrome

This will test whether IC14, an antibody that blocks CD14, can improve oxygenation in adults hospitalized with ARDS who are on mechanical ventilation.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 56 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Implicit Bioscience (Industry-sponsored)
• Drugs / interventions: infliximab, adalimumab, certolizumab, golimumab, tocilizumab, sarilumab, siltuximab
• Locations: 2 sites (Seattle, Washington and 1 other locations)
• Trial ID: NCT06513949 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled Phase 2 study testing IC14, a recombinant chimeric anti-CD14 monoclonal antibody, in adults hospitalized with ARDS. Eligible patients are intubated and enrolled early in ARDS, then randomized to receive IV IC14 or placebo and followed for 28 days. The primary endpoint is the day 4 Oxygenation Index, a measure that combines hypoxemia and ventilatory support intensity, and secondary/exploratory endpoints include inflammatory markers, duration of mechanical ventilation, and mortality. PK/PD sampling includes measuring IC14 levels in serum and bronchoalveolar fluid and exploring presepsin as a pathway-specific biomarker.

Who should consider this trial

Good fit: Adults (18+) with ARDS by Berlin criteria within 48 hours who are mechanically ventilated (P:F ratio <300 with PEEP ≥5 and bilateral chest opacities) and who can provide informed consent or have a legally authorized representative.

Not a fit: Patients who are not mechanically ventilated, have respiratory failure primarily due to cardiac failure or fluid overload, are outside the early ARDS window (>48 hours), or have contraindications to the investigational drug are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, IC14 could reduce the severity of lung injury, improve oxygenation, and potentially shorten time on mechanical ventilation for patients with ARDS.

How similar studies have performed: Preclinical data and limited early clinical work support targeting CD14 in inflammatory lung injury, but clinical evidence in ARDS remains limited and this approach is still exploratory.

Eligibility criteria

Inclusion Criteria:

Patients may be included in the study only if they meet all the following criteria:

1. Adult patients (18+) on mechanical ventilations with acute respiratory distress syndrome (ARDS) by Berlin Criteria (≤48 hours)

   1. P:F ratio \< 300
   2. Positive end-expiratory pressure (PEEP) ≥5 cm H2O
   3. Bilateral opacities on chest x-ray or chest computerized tomography (CT)-- not fully explained by effusions, lobar/lung collapse, or nodules
   4. Respiratory failure not fully explained by cardiac failure or fluid overload
   5. Within 1 week of known clinical insult or new or worsening respiratory symptoms

   i. Common Risk Factors for ARDS: Pneumonia, aspiration, inhalation injury, pulmonary contusion, pulmonary vasculitis, drowning, non-pulmonary sepsis, major trauma, pancreatitis, severe burns, non-cardiogenic shock, drug overdose, multiple transfusions
2. Patient or Legal authorized representative able to understand and give written informed consent

Exclusion Criteria:

An individual fulfilling any of the following criteria should be excluded from enrollment in the study:

1. Significant pre-existing organ dysfunction prior to hospitalization

   1. Lung: Currently receiving home oxygen therapy as documented in medical record
   2. Heart: Pre-existing congestive heart failure defined as an ejection fraction \<20% as documented in the medical record
   3. Renal: End-stage renal disease requiring renal replacement therapy or estimated glomerular filtration rate (eGFR) \<30 mL/min.
   4. Liver: Severe chronic liver disease defined as Child-Pugh Class C or hepatic transaminases \>5 times upper limit of normal
   5. Hematologic: Baseline platelet count \<50,000/mm3
2. Presence of co-existing infection, including, but not limited to:

   1. HIV infection not virally suppressed and with pre-hospitalization CD4 counts ≤ 500 cell/mm3
   2. Active tuberculosis or a history of inadequately treated tuberculosis
   3. Active hepatitis B or hepatitis C viral infection
3. Current treatment, or treatment within 30 days or five half-lives (whichever is longer) with etanercept (Enbrel®), infliximab (Remicade®), adalimumab (Humira®), certolizumab (Cimzia®), golimumab (Simponi®), anakinra (Kineret®), rilonacept (Arcalyst®), tocilizumab (Actemra®), sarilumab (Kevzara®), siltuximab (Sylvant®), or other potent immunosuppressant or immunomodulatory drugs or treatments
4. Receiving comfort measures only
5. Requiring \>2 vasopressors
6. Pregnant
7. Prisoners
8. History of hypersensitivity or idiosyncratic reaction to IC14
9. Women who are currently breastfeeding
10. Bronchoscopy safety exclusions

    1. P:F \<100 on 100% FiO2
    2. Mean pulmonary artery pressure \> 55 mmHg
    3. Marked cardiovascular instability (Mean arterial pressure \<55 mmHg with vasopressor support)
    4. Intracranial pressure ≥20 mmHg
    5. Acute ischemic heart disease (unstable angina or ST-elevation myocardial infarction or Type 1 non-ST-elevation myocardial infarction)
    6. Supported on extracorporeal membrane oxygenation
    7. Endotracheal tube \<6.5 mm

Where this trial is running

Seattle, Washington and 1 other locations

• Harborview Medical Center — Seattle, Washington, United States (Recruiting)
• University of Washington — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Linzee Mabrey, MD, MsC — Unversity of Washington
• Study coordinator: Linzee Mabrey, MD, MSc

Conditions Acute Respiratory Distress Syndrome; Adult Respiratory Distress Syndrome; Acute Lung Injury; Acute Lung Injury/Acute Respiratory Distress Syndrome; ARDS; IC14