Anti-CD14 Treatment with IC14 in Hospitalized ARDS Patients

Phase 2

Not yet recruiting

• Conditions: Adult Respiratory Distress Syndrome; Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS); Acute Lung Injury; Acute Respiratory Distress Syndrome
• Interventions: Biological: Atibuclimab; Other: Placebo

• Registration Number: NCT06513949
• Lead Sponsor: Implicit Bioscience

Brief Summary

Hospitalized patients with ARDS will be randomized to intravenous treatment with a monoclonal antibody against CD14, called IC14, or placebo. They will be followed for 28 days.

The primary outcome is the day 4 oxygenation index assessed as a continuous measure.

Detailed Description

This is a 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 (ARDS). CD14 is a key mediator in recognition of molecular markers of tissue damage (damage-associated molecular patterns, DAMPs) and infection (pathogen-associated molecular patterns, PAMPS).

The primary objective of the study is to determine the efficacy of IC14 in patients hospitalized with ARDS for reducing the severity of lung injury as measured by the day 4 Oxygenation Index (OI) assessed as a continuous measure (mean airway pressure x fraction of inspired oxygen \[FiO2\] x 100/partial pressure of oxygen \[PaO2\]). OI captures severity of hypoxemia and concurrent intensity of ventilatory support.

Secondary objectives include determining whether IC14 reduces the systemic and alveolar inflammatory response, and improves indices of oxygenation and illness severity. Exploratory endpoints include determining the effect of CD14 blockade on duration of mechanical ventilation and mortality in patients hospitalized with ARDS. Pharmacokinetic \[PK\]/Pharmacodynamic \[PD\] endpoints include determining day 4 IC14 levels in bronchoalveolar fluid (BALF) vs. serum, and determining the feasibility of measuring blood presepsin levels, a CD14-pathway specific biomarker for rapid assessment.

Study Timeline

• Study First Submitted: 2024-06-27
• Study First Submitted QC: 2024-07-19
• Study First Posted: 2024-07-22
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-05
• Last Update Posted: 2024-11-07
• Study Start: 2025-05
• Primary Completion: 2026-06
• Study Completion: 2026-08

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 56

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IC14 (atibuclimab)	Atibuclimab	IC14 (atibuclimab) is a recombinant monoclonal antibody against human CD14
Identical-appearing placebo	Placebo	Sterile normal saline

Primary Outcome Measures

Name	Time	Method
Day 4 Oxygenation Index	Day 1 through Day 4	(mean airway pressure x fraction of inspired oxygen \[FiO2\] x100)/ partial pressure of oxygen \[PaO2\]

Secondary Outcome Measures

Name	Time	Method
Biomarkers of injury and inflammation measured in bronchoalveolar lavage fluid	Day 4	Interleukin(IL)-6
Biomarkers of injury and inflammation measured in plasma	Day 4	Interleukin(IL)-6
P:F ratio	Days 4, 7, and 14	Ratio of partial pressure of arterial oxygen (P) to fraction of inspired oxygen (F)
Oxygenation index	Days 7 and 14	(mean airway pressure x FiO2 x100)/PaO2
Oxygen saturation index	Days 4, 7, and 14	(mean airway pressure x FiO2 x100)/peripheral oxygen saturation \[SpO2\]
S:F ratio	Days 4, 7, and 14	Ratio of the arterial oxygen saturation (S) to fraction of inspired oxygen (F)
Sequential Organ Failure Assessment (SOFA) Score (range 0 [best] to 24 [worst])	Days 4, 7, and 14	Disease severity scale
Time to blood presepsin level	Days 0-4	Time from study consent to measurement completion of blood presepsin level via the PATHFASTTM instrument
Cumulative incidence of run failures	Days 0-1	Defined as not completing presepsin measurement between consent and infusion of study drug
Cumulative incidence of protocol-specified exempt serious events	Days 1-28	protocol-specified exempt serious events
Cumulative incidence of grade 3 and 4 clinical and laboratory adverse events	Days 1-28	Common Toxicity Criteria for Adverse Events version 5.0
Cumulative incidence of serious adverse events	Days 1-28	Serious adverse events standard definition
Cumulative incidence of adverse events of special interest	Days 1-28	Adverse events of special interest for test article and bronchoalveolar lavage

Trial Locations

Locations (1)

University of Washington; 🇺🇸 Seattle, Washington, United States