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Compassionate Use Open-Label Anti-CD14 Treatment in Patients With SARS-CoV-2 (COVID-19)

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ClinicalTrials.gov Identifier: NCT04346277
Expanded Access Status : Available
First Posted : April 15, 2020
Last Update Posted : June 24, 2020
Sponsor:
Information provided by (Responsible Party):
Implicit Bioscience

Brief Summary:

This protocol proposes to use IC14, a recombinant chimeric monoclonal antibody (mAb) recognizing human CD14, to block CD14-mediated cellular activation in patients early in the development of ARDS. The binding of IC14 to human CD14 prevents CD14 from participating in the recognition of PAMPs and DAMPs due to SARS-CoV-2 infection. The putative mechanism of action of IC14 in ARDS is blockade of PAMP and DAMP interactions with CD14, thus attenuating the inflammatory cascade that leads to increased endothelial and epithelial permeability and injury resulting in alveolar injury and fluid accumulation characteristic of ARDS.

IC14 is a chimeric monoclonal antibody that binds to CD14 with high affinity and inhibits signaling via membrane and soluble CD14. Blocking CD14 with IC14 treatment in normal volunteers strongly inhibits systemic inflammation in response to bacterial endotoxin (LPS). University of Washington conducted a small NIH-funded pilot trial of IC14 treatment in 13 patients with ARDS, which suggested that IC14 treatment reduced alveolar inflammation and decreased BAL cytokines. IC14 was also the subject of IND 105803 for a phase 2 study of ARDS from all causes which we propose to revise for the COVID-19 indication.

A dosing regimen for IC14 with favorable pharmacokinetics supporting once daily intravenous dosing has been defined, making this an acceptable treatment for hospitalized patients. Two pharmacodynamic biomarkers can be used that are related to CD14, measurements of sCD14 (serum at baseline; urine at baseline and follow up) as well as a CD14 fragment (sCD14-ST; presepsin). A CD14 target engagement assay is available.

Therefore, because of the central role of CD14 in the amplification of lung inflammatory responses leading to severe lung injury and the safety record of IC14 in humans, we propose to have an open-label protocol to test the safety and potential efficacy of IC14 treatment in preventing the progression of severe respiratory disease in patients hospitalized with COVID-19.


Condition or disease Intervention/treatment
COVID ARDS, Human Ards SARS-CoV2 Biological: IC14, a monoclonal antibody against CD14

Detailed Description:

This is a compassionate use open label program in patients hospitalized with pulmonary complications of SARS-CoV-2 infection who will receive IC14 at a dosage of 4 mg/kg on Day 1, then 2 mg/kg once daily on Days 2-4. Patient monitoring will be for a total of up to 28 days if the patient is still hospitalized.

Screening/baseline assessments and initiation of the first IC14 administration will occur within 48 hours after meeting inclusion criteria. IC14 should be administered at approximately 24-hr intervals beginning from the start time of the first IC14 administration (Day 1).

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Study Type : Expanded Access
Expanded Access Type : Intermediate-size Population
  See clinical trials of the intervention/treatment in this expanded access record.
Official Title: Compassionate Use Open-Label Anti-CD14 Treatment in Patients With SARS-CoV-2 (COVID-19)



Intervention Details:
  • Biological: IC14, a monoclonal antibody against CD14
    IC14 is a recombinant chimeric anti-human monoclonal antibody directed against human CD14. It recognizes both membrane-bound CD14 and soluble CD14.
    Other Name: anti-CD14

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Criteria

Inclusion Criteria:

  1. Signed informed consent form and able to give informed consent
  2. Age 18-70 years
  3. Presence of a SARS-CoV-2 infection documented by nasopharyngeal swab positive by RT-PCR testing or history of positive test
  4. Radiologic findings compatible with diagnosis of SARS-CoV-2 pulmonary infection
  5. Hypoxemia as defined by any of the following:

    1. SpO2 ≤92% on room air
    2. Requirement for >2L O2 per standard nasal cannula
    3. PaO2/FiO2<300 if on high-flow nasal cannula
  6. Women of childbearing potential must have a negative pregnancy test

Exclusion Criteria:

A patient fulfilling any of the following criteria is to be excluded from enrollment in the study:

  1. Intubation
  2. Do-not-attempt resuscitation (DNAR) / do not intubate status
  3. Anticipated survival <48 hours
  4. Anticipated survival <28 days due to pre-existing medical condition
  5. Significant pre-existing organ dysfunction

    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: Chronic renal failure requiring renal replacement therapy
    4. Liver: Severe chronic liver disease defined as Child-Pugh Class C
  6. Pre-existing, ongoing immunosuppression

    1. Solid organ transplant recipient
    2. Chronic high-dose corticosteroids (equivalent to >20 mg/prednisone/day for >14 days in the last 30 days)
    3. Oncolytic drug therapy within the past 14 days
    4. Known HIV positive with CD4 count <200 cells/mm3
  7. Current treatment with Enbrel® (etanercept), Remicade® (infliximab), Humira® (adalimumab), Cimzia® (certolizumab), or Simponi® (golimumab), Kineret® (anakinra), Arcalyst® (rilonacept), or other potent immunosuppressant
  8. Pregnancy
  9. History of hypersensitivity or idiosyncratic reaction to IC14

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04346277


Contacts
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Contact: Lorenzo Dagna, MD +39-02-26434683 dagna.lorenzo@unisr.it

Locations
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Italy
IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University Available
Milano, Italy, 20132
Sponsors and Collaborators
Implicit Bioscience
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Responsible Party: Implicit Bioscience
ClinicalTrials.gov Identifier: NCT04346277    
Other Study ID Numbers: COV02
First Posted: April 15, 2020    Key Record Dates
Last Update Posted: June 24, 2020
Last Verified: April 2020
Keywords provided by Implicit Bioscience:
coronavirus
acute lung injury
Additional relevant MeSH terms:
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Respiratory Distress Syndrome, Adult
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs