Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection
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|ClinicalTrials.gov Identifier: NCT04381052|
Recruitment Status : Not yet recruiting
First Posted : May 8, 2020
Last Update Posted : May 8, 2020
|Condition or disease||Intervention/treatment||Phase|
|COVID-19||Drug: Clazakizumab Other: Placebo||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||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.|
|Masking:||Double (Participant, Investigator)|
|Masking Description:||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.|
|Official Title:||A Randomized Placebo-Controlled Safety and Dose-Finding Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection|
|Estimated Study Start Date :||May 2020|
|Estimated Primary Completion Date :||August 1, 2020|
|Estimated Study Completion Date :||August 1, 2020|
Experimental: 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.
Dose is 25mg intravenously over 30 minutes.
Placebo Comparator: 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.
Intravenously administered over 30 minutes.
- Cumulative incidence of serious adverse events associated with clazakizumab or placebo [ Time Frame: 60 days ]
- Cumulative Incidence of Intubation [ Time Frame: 14 days ]
- Time to Extubation [ Time Frame: 14 days ]
- Length of Intensive Care Unit (ICU) stay [ Time Frame: 14 days ]
- Number of Patients who Present a Decrease in C-reactive protein (CRP) [ Time Frame: 14 days ]
- Number of Patients with Acute Kidney Injury (AKI) [ Time Frame: 14 days ]
- Number of Patients with a Need for Renal Replacement Therapy (RRT) [ Time Frame: 14 days ]
- Duration of Renal Replacement Therapy (RRT) [ Time Frame: 60 days ]
- Patient Survival [ Time Frame: 28 days ]Number of participants alive at day 28.
- Patient Survival [ Time Frame: 60 days ]Number of participants alive at day 60, end of study.
- Number of Patients with Hemodialysis [ Time Frame: 60 days ]
- Number of Patients with Continuous Renal Replacement Therapies (CRRT) [ Time Frame: 60 days ]
- Number of Patients with Peritoneal Dialysis [ Time Frame: 60 days ]
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): NCT04381052
|Contact: David J. Cohen, MDfirstname.lastname@example.org|
|Contact: Melanie Foleyemail@example.com|
|Principal Investigator:||David J. Cohen, MD||Columbia University|