COVIDNCT04346277
Compassionate Use Open-Label Anti-CD14 Treatment in Patients With SARS-CoV-2 (COVID-19)
A study testing IC14, a monoclonal antibody against CD14 in people with COVID and ARDS, Human, run by Implicit Bioscience at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- COVID, ARDS, Human, Ards
- What is being tested?
- IC14, a monoclonal antibody against CD14
- How many people
- Not given
- Where
- 1 siteItaly
- Study dates
- Start not givento not given
- Phase
- Expanded access
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Adult, Older adult
Who may be able to join
- Signed informed consent form and able to give informed consent
- Age 18-70 years
- Presence of a SARS-CoV-2 infection documented by nasopharyngeal swab positive by RT-PCR testing or history of positive test
- Radiologic findings compatible with diagnosis of SARS-CoV-2 pulmonary infection
- Hypoxemia as defined by any of the following:
- SpO2 ≤92% on room air
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- Requirement for >2L O2 per standard nasal cannula
- PaO2/FiO2<300 if on high-flow nasal cannula
- Women of childbearing potential must have a negative pregnancy test
Who cannot join
- A patient fulfilling any of the following criteria is to be excluded from enrollment in the study:
- Intubation
- Do-not-attempt resuscitation (DNAR) / do not intubate status
- Anticipated survival <48 hours
- Anticipated survival <28 days due to pre-existing medical condition
- Significant pre-existing organ dysfunction
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- Lung: Currently receiving home oxygen therapy as documented in medical record
- Heart: Pre-existing congestive heart failure defined as an ejection fraction <20% as documented in the medical record
- Renal: Chronic renal failure requiring renal replacement therapy
- Liver: Severe chronic liver disease defined as Child-Pugh Class C
- Pre-existing, ongoing immunosuppression
- Solid organ transplant recipient
- Chronic high-dose corticosteroids (equivalent to >20 mg/prednisone/day for >14 days in the last 30 days)
- Oncolytic drug therapy within the past 14 days
- Known HIV positive with CD4 count <200 cells/mm3
- Current treatment with Enbrel® (etanercept), Remicade® (infliximab), Humira® (adalimumab), Cimzia® (certolizumab), or Simponi® (golimumab), Kineret® (anakinra), Arcalyst® (rilonacept), or other potent immunosuppressant
- Pregnancy
- History of hypersensitivity or idiosyncratic reaction to IC14
Trial locations and contacts
1 site in 1 country.
Italy1 site
IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University
Milan, 20132
About this study
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.
Read more
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.
Read the 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).
- Conditions
- COVID, ARDS, Human, Ards, SARS-CoV2
- Being tested
- IC14, a monoclonal antibody against CD14
- Keywords
- coronavirus, acute lung injury
- Medical subject headings
- Respiratory Distress Syndrome, Acute Lung Injury, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IC14, a monoclonal antibody against CD14Biological
Also called anti-CD14
IC14 is a recombinant chimeric anti-human monoclonal antibody directed against human CD14. It recognizes both membrane-bound CD14 and soluble CD14.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVIDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Expanded access
Sponsor and investigators
- Lead sponsor
- Implicit Bioscience
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04346277
- Sponsor's protocol ID
- COV02
- Status last verified
- Jun 2021
- First submitted
- 13 Apr 2020
- Last updated
- 21 Jun 2021
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Compassionate Use Open-Label Anti-CD14 Treatment in Patients With SARS-CoV-2 (COVID-19)
- ClinicalTrials.gov ID
- NCT04346277
- Acronym / sponsor ID
- COV02
- Conditions
- COVID, ARDS, Human, Ards, SARS-CoV2
- Keywords
- coronavirus, acute lung injury
- Study type
- Expanded access
- Recruitment status
- No Longer Available
- Lead sponsor
- Implicit BioscienceIndustry (pharma, biotech, devices)
- First posted
- 15 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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).
Study design
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Signed informed consent form and able to give informed consent
- Age 18-70 years
- Presence of a SARS-CoV-2 infection documented by nasopharyngeal swab positive by RT-PCR testing or history of positive test
- Radiologic findings compatible with diagnosis of SARS-CoV-2 pulmonary infection
- Hypoxemia as defined by any of the following:
Key exclusion criteria (18 listed)
- A patient fulfilling any of the following criteria is to be excluded from enrollment in the study:
- Intubation
- Do-not-attempt resuscitation (DNAR) / do not intubate status
- Anticipated survival <48 hours
- Anticipated survival <28 days due to pre-existing medical condition
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IC14, a monoclonal antibody against CD14Also: anti-CD14IC14 is a recombinant chimeric anti-human monoclonal antibody directed against human CD14. It recognizes both membrane-bound CD14 and soluble CD14. | Biological | – |
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing IC14, a monoclonal antibody against CD14 in people with COVID and ARDS, Human, run by Implicit Bioscience at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2021; AzTrials last refreshed its copy on 7 Nov 2026.