Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04381052
Recruitment Status : Not yet recruiting
First Posted : May 8, 2020
Last Update Posted : May 8, 2020
Sponsor:
Collaborators:
NYU Langone Health
Vitaeris INC
Information provided by (Responsible Party):
Columbia University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Clazakizumab Other: Placebo Phase 2

Detailed Description:

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
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.
Primary Purpose: Treatment
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

Arm Intervention/treatment
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.
Drug: Clazakizumab
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.
Other: Placebo
Intravenously administered over 30 minutes.




Primary Outcome Measures :
  1. Cumulative incidence of serious adverse events associated with clazakizumab or placebo [ Time Frame: 60 days ]

Secondary Outcome Measures :
  1. Cumulative Incidence of Intubation [ Time Frame: 14 days ]
  2. Time to Extubation [ Time Frame: 14 days ]
  3. Length of Intensive Care Unit (ICU) stay [ Time Frame: 14 days ]
  4. Number of Patients who Present a Decrease in C-reactive protein (CRP) [ Time Frame: 14 days ]
  5. Number of Patients with Acute Kidney Injury (AKI) [ Time Frame: 14 days ]
  6. Number of Patients with a Need for Renal Replacement Therapy (RRT) [ Time Frame: 14 days ]
  7. Duration of Renal Replacement Therapy (RRT) [ Time Frame: 60 days ]
  8. Patient Survival [ Time Frame: 28 days ]
    Number of participants alive at day 28.

  9. Patient Survival [ Time Frame: 60 days ]
    Number of participants alive at day 60, end of study.

  10. Number of Patients with Hemodialysis [ Time Frame: 60 days ]
  11. Number of Patients with Continuous Renal Replacement Therapies (CRRT) [ Time Frame: 60 days ]
  12. Number of Patients with Peritoneal Dialysis [ Time Frame: 60 days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

In order to be eligible to participate in this study, the patients must meet all of the following criteria:

  1. At least 18 years of age
  2. 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.
  3. 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

  4. 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.)
  5. 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:

    1. combined (estrogen and progestogen containing) hormonal contraception combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, or transdermal)
    2. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
    3. intrauterine device (IUD)
    4. intrauterine hormone-releasing system (IUS)
    5. vasectomized partner
    6. bilateral tubal occlusion
    7. true abstinence. when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence, such as calendar, ovulation, symptothermal, postovulation methods, and withdrawal are not acceptable methods of contraception.
  6. 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:

  1. Evidence of irreversible injury deemed non-survivable even if the pulmonary failure recovers (for example severe anoxic brain injury)
  2. Known active inflammatory bowel disease
  3. Known active, untreated diverticulitis
  4. Known untreated bacteremia
  5. Pregnancy. (The protocol will exclude pregnant subjects given the lack of overall data on use of clazakizumab in pregnancy however the study team would consider a protocol revision should more than 3 potential pregnant study subjects be excluded on this basis).
  6. Known hypersensitivity to the clazakizumab

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): NCT04381052


Contacts
Layout table for location contacts
Contact: David J. Cohen, MD 212-305-3273 djc5@cumc.columbia.edu
Contact: Melanie Foley 212-305-5038 mf2162@cumc.columbia.edu

Locations
Layout table for location information
United States, New York
Columbia University Medical Center / New York Presbyerian Hospital
New York, New York, United States, 10032
Contact: David J Cohen, MD    212-305-3273    djc5@cumc.columbia.edu   
Contact: Melanie Foley    212-305-5038    mf2162@cumc.columbia.edu   
Sponsors and Collaborators
Columbia University
NYU Langone Health
Vitaeris INC
Investigators
Layout table for investigator information
Principal Investigator: David J. Cohen, MD Columbia University
Layout table for additonal information
Responsible Party: Columbia University
ClinicalTrials.gov Identifier: NCT04381052    
Other Study ID Numbers: AAAT0142
First Posted: May 8, 2020    Key Record Dates
Last Update Posted: May 8, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Coded data will be shared with New York University (NYU) Langone for the purpose of statistical analysis and scientific reporting.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Columbia University:
Coronavirus
SARS-COVID-2
Additional relevant MeSH terms:
Layout table for MeSH terms
Infection