- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04346277
Compassionate Use Open-Label Anti-CD14 Treatment in Patients With SARS-CoV-2 (COVID-19)
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.
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Expanded Access Type
- Intermediate-size Population
Contacts and Locations
Study Locations
-
-
-
Milano, Italy, 20132
- IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
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
- 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
Study Plan
How is the study designed?
Collaborators and Investigators
Sponsor
Study record dates
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- COV02
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on COVID
-
European Institute of OncologyFondazione I.R.C.C.S. Istituto Neurologico Carlo Besta; Azienda Ospedaliera... and other collaboratorsCompleted
-
Owlstone LtdCambridge University Hospitals NHS Foundation TrustCompleted
-
Erasmus Medical CenterDa Vinci Clinic; HGC RijswijkNot yet recruitingPost-COVID-19 Syndrome | Long COVID | Long Covid19 | Post COVID-19 Condition | Post-COVID Syndrome | Post COVID-19 Condition, Unspecified | Post-COVID ConditionNetherlands
-
Sultan Qaboos UniversityCompletedCOVID-19 | Non-CovidOman
-
Assiut UniversityRecruiting
-
Jilin UniversityUnknown
-
Indonesia UniversityRecruitingPost-COVID-19 Syndrome | Long COVID | Post COVID-19 Condition | Post-COVID Syndrome | Long COVID-19Indonesia
-
University of Roma La SapienzaQueen Mary University of London; Università degli studi di Roma Foro Italico; Bios Prevention SrlCompletedPost Acute Sequelae of COVID-19 | Post COVID-19 Condition | Long-COVID | Chronic COVID-19 SyndromeItaly
-
Miami VA Healthcare SystemNot yet recruiting
Clinical Trials on IC14, a monoclonal antibody against CD14
-
Implicit BioscienceRoyal Brisbane and Women's HospitalCompletedMotor Neuron Disease | Amyotrophic Lateral SclerosisAustralia
-
Implicit BioscienceWithdrawnAcute Respiratory Distress Syndrome
-
Implicit BioscienceWithdrawnAmyotrophic Lateral SclerosisAustralia
-
National Institute of Allergy and Infectious Diseases...PPD; University of Washington; Vanderbilt University Medical Center; Implicit BioscienceTerminatedSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) | Coronavirus Disease 2019 (COVID-19)United States
-
Probiomed S.A. de C.V.UnknownDiffuse Large B Cell LymphomaMexico
-
BiocadCompleted
-
Bio-Thera SolutionsTerminated
-
Bio-Thera SolutionsActive, not recruitingPlaque PsoriasisChina
-
Shanghai Junshi Bioscience Co., Ltd.RecruitingModerate to Severe Chronic Plaque PsoriasisChina
-
Great Ormond Street Hospital for Children NHS Foundation...CompletedJuvenile Myelomonocytic Leukemia | Acute Lymphoblastic Leukemia | Acute Myeloblastic LeukemiaUnited Kingdom