Clinical trial NCT06513949: Anti-CD14 Treatment with IC14 in Hospitalized ARDS Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Acute Respiratory Distress Syndrome
Adult Respiratory Distress Syndrome
Acute Lung Injury
Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
Keywords: ARDS
IC14
Lead sponsor: Implicit Bioscience
Sponsor class: INDUSTRY
Collaborators: name: University of Washington
First posted: 2024-07-22
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients hospitalized with ARDS will be randomized to treatment with anti-CD14 monoclonal antibody, IC14, or placebo and evaluated for impact of treatment on severity of lung injury as measured by day 4 oxygenation index. Secondary objectives include determination of systemic and alveolar inflammatory responses; indices of oxygenation and illness severity; safety; and IC14 levels in bronchoalveolar lavage fluid and serum. Exploratory objectives include determining the effect of treatment on duration of mechanical ventilation, mortality, and feasibility of measuring presepsin, a CD14 pathway-specific biomarker at baseline using rapid testing
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Day 4 Oxygenation Index
timeFrame: Day 1 through Day 4
Secondary outcomes:
measure: Biomarkers of injury and inflammation measured in bronchoalveolar lavage fluid
timeFrame: Day 4
measure: Biomarkers of injury and inflammation measured in plasma
timeFrame: Day 4
measure: Oxygenation index
timeFrame: Days 7 and 14
measure: Oxygen saturation index
timeFrame: Days 4, 7, and 14
measure: P:F ratio
timeFrame: Days 4, 7, and 14
measure: S:F ratio
timeFrame: Days 4, 7, and 14
measure: Sequential Organ Failure Assessment (SOFA) Score (range 0 [best] to 24 [worst])
timeFrame: Days 4, 7, and 14
measure: Time to blood presepsin level
timeFrame: Days 0-4
measure: Cumulative incidence of run failures
timeFrame: Days 0-1
measure: Cumulative incidence of protocol-specified exempt serious events
timeFrame: Days 1-28
measure: Cumulative incidence of grade 3 and 4 clinical and laboratory adverse events
timeFrame: Days 1-28
measure: Cumulative incidence of serious adverse events
timeFrame: Days 1-28
measure: Cumulative incidence of adverse events of special interest
timeFrame: Days 1-28
Other outcomes:
measure: Ventilator-free Days
timeFrame: Days 1-28
measure: Mortality
timeFrame: Day 1-28
Locations:
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Unversity of Washington
name: Linzee Mabrey, MD, MsC
role: PRINCIPAL_INVESTIGATOR
References: