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Study terminated due to poor enrollment. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1).
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| Name | Class |
|---|---|
| NYU Langone Health | OTHER |
| CSL Behring | INDUSTRY |
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In this study, the investigators propose to administer clazakizumab to patients with life-threatening Coronavirus Disease 2019 (COVID-19) infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 30 patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms and receive clazakizumab at a dose of 25 mg or placebo.
The limited understanding of the clinical behavior of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (the viral organism responsible for COVID-19 disease) is evolving on a daily basis. Reports from China indicate that a subset of patients with the worst clinical outcomes may manifest cytokine storm syndrome. Hypotheses that excess cytokines may trigger a secondary hemophagocytic lymphohistiocytosis (sHLH) have been proposed. Indeed, cytokine profiles consistent with this picture were observed in Chinese patients with severe pulmonary involvement. Specifically, elevated ferritin and interleukin-6 (IL-6) were associated with fatalities among the infected patients. A role for targeted anti-inflammatory and anti-cytokine therapies in the treatment of pulmonary hyperinflammation has been proposed.
Clazakizumab is a genetically engineered humanized immunoglobulin-1 (IgG1) monoclonal antibody (mAb) that binds with high affinity to human IL-6. This investigational agent is currently being studied as a treatment for chronic active antibody mediated rejection of renal allografts.
In this study investigators propose to administer clazakizumab to patients with life-threatening pulmonary failure secondary to COVID-19 disease.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Clazakizumab 25 mg | Experimental | The first dose will be administered as soon as possible after the patient is enrolled and randomized into the Clazakizumab 25 mg arm. The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes. Serum C-reactive protein (CRP) will be evaluated at baseline and on days 1 and 2 following clazakizumab administration. If the CRP does not decrease by 50% within 36-48 hours after the first dose, a second dose of 25 mg clazakizumab will be given no later than day 3. |
|
| Placebo | Placebo Comparator | The first dose will be administered as soon as possible after the patient is enrolled and randomized into the Placebo arm. The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes. Serum CRP will be evaluated at baseline and on days 1 and 2 following clazakizumab administration. If the CRP does not decrease by 50% within 36-48 hours after the first dose, a second dose of placebo will be given no later than day 3. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clazakizumab | Drug | Dose is 25mg intravenously over 30 minutes. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative Incidence of Serious Adverse Events Associated With Clazakizumab or Placebo | 60 days |
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative Incidence of Intubation | 14 days | |
| Time to Extubation | 14 days | |
| Length of Intensive Care Unit (ICU) Stay |
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Inclusion Criteria:
In order to be eligible to participate in this study, the patients must meet all of the following criteria:
At least 18 years of age
Confirmed COVID-19 disease (by Cobas SARS-CoV-2 real time reverse transcription polymerase chain reaction (RT-PCR) using nasopharyngeal swab sample, or equivalent test available to be performed by the Columbia University Irving Medical Center (CUIMC)/New York Presbyterian (NYP) clinical laboratory). Effort will be made to have the confirmatory test result <72 hours prior to enrollment however given overall clinical demand this may not be feasible in all cases.
Respiratory failure manifesting as: Acute Respiratory Distress Syndrome (defined by a P/F ratio of <200), OR oxygen saturation (SpO2) < 90% on 4 liters (L) (actual or expected given higher O2 requirement) OR increasing O2 requirements over 24 hours, plus 2 or more of the following predictors for severe disease:
CRP > 35 mg/L Ferritin > 500 ng/mL D-dimer > 1 mcg/L Neutrophil-Lymphocyte Ratio > 4 Lactate dehydrogenase (LDH) > 200 U/L Increase in troponin in patient w/out known cardiac disease
Has a consent designee willing to provide informed consent on behalf of the patient (this assumes that a mechanically ventilated patients lacks capacity to consent on his/her own behalf. Should it be deemed that the patient has capacity to consent, consent may be obtained from the patient.)
Women of childbearing potential must be willing and able to use at least one highly effective contraceptive method for a period of 5 months following the study drug administration. In the context of this study, an effective method is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly such as:
Men must be willing to use a double-barrier contraception from enrollment until at 5 months after the last dose of study drug, if not abstinent.
Exclusion Criteria:
An individual who meets any of the following criteria will be excluded from participation in this study:
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| Name | Affiliation | Role |
|---|---|---|
| David J. Cohen, MD | Columbia University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Columbia University Medical Center / New York Presbyerian Hospital | New York | New York | 10032 | United States |
Coded data will be shared with New York University (NYU) Langone for the purpose of statistical analysis and scientific reporting.
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Study was closed due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed.
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| ID | Title | Description |
|---|---|---|
| FG000 | Clazakizumab 25 mg or Placebo | The first dose will be administered as soon as possible after the patient is enrolled and randomized into a specific arm. The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes. Serum CRP will be evaluated at baseline and on days 1 and 2 following first dose administration. If the CRP does not decrease by 50% within 36-48 hours after the first dose, a second dose of placebo will be given no later than day 3. Placebo: Intravenously administered over 30 minutes. OR Clazakizumab: Dose is 25mg intravenously over 30 minutes. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Study was closed due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed.
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| ID | Title | Description |
|---|---|---|
| BG000 | Clazakizumab 25 mg | The first dose will be administered as soon as possible after the patient is enrolled and randomized into the Clazakizumab 25 mg arm. The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes. Serum C-reactive protein (CRP) will be evaluated at baseline and on days 1 and 2 following clazakizumab administration. If the CRP does not decrease by 50% within 36-48 hours after the first dose, a second dose of 25 mg clazakizumab will be given no later than day 3. Clazakizumab: Dose is 25mg intravenously over 30 minutes. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cumulative Incidence of Serious Adverse Events Associated With Clazakizumab or Placebo | Study stopped due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed. | Posted | 60 days |
|
Up to 60 days
Study stopped due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Clazakizumab 25 mg | The first dose will be administered as soon as possible after the patient is enrolled and randomized into the Clazakizumab 25 mg arm. The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes. Serum C-reactive protein (CRP) will be evaluated at baseline and on days 1 and 2 following clazakizumab administration. If the CRP does not decrease by 50% within 36-48 hours after the first dose, a second dose of 25 mg clazakizumab will be given no later than day 3. Clazakizumab: Dose is 25mg intravenously over 30 minutes. |
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Study was closed due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David J. Cohen, MD | Columbia University | 212-305-3273 | djc5@cumc.columbia.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 4, 2020 | Apr 1, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D018352 | Coronavirus Infections |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C000604955 | clazakizumab |
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This is a randomized, double-blind, placebo-controlled, adaptive seamless Phase II/III design (ASD). The investigators propose the administration of an investigational drug in patients with high predicted short-term mortality secondary to COVID-19 disease. Patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms that will receive clazakizumab at a dose of 25 mg or placebo.
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This study is double-blind and therefore neither the Investigator, the subject, the Sponsor and its representatives, nor other designated study site personnel involved in running of the study will be aware of the identification of the investigational drug administered to each subject.
| Placebo | Other | Intravenously administered over 30 minutes. |
|
| 14 days |
| Number of Patients Who Present a Decrease in C-reactive Protein (CRP) | 14 days |
| Number of Patients With Acute Kidney Injury (AKI) | 14 days |
| Number of Patients With a Need for Renal Replacement Therapy (RRT) | 14 days |
| Duration of Renal Replacement Therapy (RRT) | 60 days |
| Patient Survival | Number of participants alive at day 28. | 28 days |
| Patient Survival | Number of participants alive at day 60, end of study. | 60 days |
| Number of Patients With Hemodialysis | 60 days |
| Number of Patients With Continuous Renal Replacement Therapies (CRRT) | 60 days |
| Number of Patients With Peritoneal Dialysis | 60 days |
| BG001 | Placebo | The first dose will be administered as soon as possible after the patient is enrolled and randomized into the Placebo arm. The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes. Serum CRP will be evaluated at baseline and on days 1 and 2 following clazakizumab administration. If the CRP does not decrease by 50% within 36-48 hours after the first dose, a second dose of placebo will be given no later than day 3. Placebo: Intravenously administered over 30 minutes. |
| BG002 | Total | Total of all reporting groups |
|
| Sex: Female, Male |
|
| Ethnicity (NIH/OMB) |
|
| Race (NIH/OMB) |
|
| Region of Enrollment | participants |
|
| OG001 |
| Placebo |
The first dose will be administered as soon as possible after the patient is enrolled and randomized into the Placebo arm. The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes. Serum CRP will be evaluated at baseline and on days 1 and 2 following clazakizumab administration. If the CRP does not decrease by 50% within 36-48 hours after the first dose, a second dose of placebo will be given no later than day 3. Placebo: Intravenously administered over 30 minutes. |
|
| Secondary | Cumulative Incidence of Intubation | Study stopped due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed. | Posted | 14 days |
|
|
| Secondary | Time to Extubation | Study stopped due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed. | Posted | 14 days |
|
|
| Secondary | Length of Intensive Care Unit (ICU) Stay | Study stopped due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed. | Posted | 14 days |
|
|
| Secondary | Number of Patients Who Present a Decrease in C-reactive Protein (CRP) | Study stopped due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed. | Posted | 14 days |
|
|
| Secondary | Number of Patients With Acute Kidney Injury (AKI) | Study stopped due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed. | Posted | 14 days |
|
|
| Secondary | Number of Patients With a Need for Renal Replacement Therapy (RRT) | Study stopped due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed. | Posted | 14 days |
|
|
| Secondary | Duration of Renal Replacement Therapy (RRT) | Study stopped due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed. | Posted | 60 days |
|
|
| Secondary | Patient Survival | Number of participants alive at day 28. | Study stopped due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed. | Posted | 28 days |
|
|
| Secondary | Patient Survival | Number of participants alive at day 60, end of study. | Study stopped due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed. | Posted | 60 days |
|
|
| Secondary | Number of Patients With Hemodialysis | Study stopped due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed. | Posted | 60 days |
|
|
| Secondary | Number of Patients With Continuous Renal Replacement Therapies (CRRT) | Study stopped due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed. | Posted | 60 days |
|
|
| Secondary | Number of Patients With Peritoneal Dialysis | Study stopped due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed. | Posted | 60 days |
|
|
| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| EG001 | Placebo | The first dose will be administered as soon as possible after the patient is enrolled and randomized into the Placebo arm. The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes. Serum CRP will be evaluated at baseline and on days 1 and 2 following clazakizumab administration. If the CRP does not decrease by 50% within 36-48 hours after the first dose, a second dose of placebo will be given no later than day 3. Placebo: Intravenously administered over 30 minutes. | 0 | 0 | 0 | 0 | 0 | 0 |
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| D014777 |
| Virus Diseases |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |