Anti-CD14 Treatment With IC14 in Hospitalized ARDS Patients

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Respiratory Distress Syndrome; Acute Lung Injury; Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS); Adult Respiratory Distress Syndrome
• Intervention / Treatment: Biological: Atibuclimab; Other: Placebo

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 Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Linzee Mabrey, MD, MSc; Phone Number: (206) 897-5051; Email: mflinzee@uw.edu

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • University of Washington
      • Contact: Linzee Mabrey, MD, MSc; Phone Number: 206-731-4165; Email: mflinzee@uw.edu
      • Principal Investigator: Eric Morrell, MD, PhD
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Harborview Medical Center
      • Contact: Linzee Mabrey, MD
      • Principal Investigator: Linzee Mabrey, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IC14 (atibuclimab); IC14 (atibuclimab) is a recombinant monoclonal antibody against human CD14	Biological: Atibuclimab; monoclonal antibody against human CD14; Other Names: IC14
Placebo Comparator: Identical-appearing placebo; Sterile normal saline	Other: Placebo; Sterile normal saline for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Day 4 Oxygenation Index	(mean airway pressure x fraction of inspired oxygen [FiO2] x100)/ partial pressure of oxygen [PaO2]	Day 1 through Day 4

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator-free Days	Days alive and free of invasive mechanical ventilation	Days 1-28
Mortality	All-cause mortality	Day 1-28

Collaborators and Investigators

• Sponsor: Implicit Bioscience
• Collaborators: University of Washington
• Investigators: Principal Investigator: Linzee Mabrey, MD, MsC, Unversity of Washington

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 27, 2024
• First Submitted That Met QC Criteria: July 19, 2024
• First Posted (Actual): July 22, 2024

Study Record Updates

• Last Update Posted (Actual): August 20, 2025
• Last Update Submitted That Met QC Criteria: August 15, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: ARDS; IC14
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Thoracic Injuries; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Wounds and Injuries; Lung Injury; Acute Lung Injury
• Other Study ID Numbers: ARDS01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No