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Use of the Interleukin-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: NCT04363502
Recruitment Status : Recruiting
First Posted : April 27, 2020
Last Update Posted : May 19, 2020
Sponsor:
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:
In this study Investigators propose to administer clazakizumab to patients with life-threatening 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 that will receive clazakizumab at a dose of 25 mg or placebo.

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

Detailed Description:

In this study Investigators propose to administer clazakizumab to patients with severe 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 three study arms that will receive clazakizumab at a dose of 25 mg or placebo.

The primary endpoint is patient safety assessed by serious adverse events associated with clazakizumab or placebo.

The secondary endpoints are: incidence of intubation, time to extubation, length of ICU stay, severity of AKI, need for RRT, duration of RRT, trend in C-reactive protein, and patient survival at 28 and 60 days.

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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, design. We propose the administration of an investigational drug in patients with high predicted short-term mortality secondary to COVID-19 disease. 30 Patients will be randomly assigned in a 1:1 ratio to two study arms that will receive clazakizumab at a dose of 25 mg or placebo.
Masking: Triple (Participant, Care Provider, Investigator)
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
Actual Study Start Date : May 7, 2020
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020

Arm Intervention/treatment
Experimental: clazakizumab at a dose of 25 mg
A first dose of 25 mg of clazakizumab will be given. No premedications will be given prior to the investigational product. Serum CRP will be evaluated at baseline and on days 1 and 2 following clazakizumab or placebo administration to assess response. If the CRP does not decrease by 50% within 36-48 hours after the first dose, a second dose of 25mg clazakizumab (an identical dose to the day 1 dose) will be given no later than day 3
Drug: Clazakizumab
The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes.
Other Name: engineered humanized mAb directed against the human cytokine IL-6

Placebo Comparator: placebo
A first dose of placebo will be given. No premedications will be given prior to the investigational product. Serum CRP will be evaluated at baseline and on days 1 and 2 following clazakizumab or placebo administration to assess response. If the CRP does not decrease by 50% within 36-48 hours after the first dose, a second dose of placebo (an identical dose to the day 1 dose) will be given no later than day 3
Drug: Placebo
The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes.




Primary Outcome Measures :
  1. Change in C-reactive protein (CRP) level [ Time Frame: Up to 3 days ]
    Serum CRP (measured in mg/dl) will be evaluated at baseline and on days 1 and 2 following clazakizumab or placebo administration to assess response



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.


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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1. At least 18 years of age
  • 2. Confirmed COVID-19 disease (by Cobas Severe Acute Respiratory Syndrome (SARS)-CoV-2 real time RT-PCR using nasopharyngeal swab sample, or equivalent test available to be performed by the Johns Hopkins Medical Laboratories Services). 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 SpO2 < 90% on 4L (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
    • 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:

  • 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
  • 7. Use of other IL-6 inhibitor investigational drugs at the time of enrollment

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): NCT04363502


Contacts
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Contact: Nada Alachkar, MD 410-614-9225 nalachk1@jhmi.edu
Contact: Russell Wesson, MD 180042124571 rwesson1@jhmi.edu

Locations
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United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Nada Alachkar         
Sponsors and Collaborators
Johns Hopkins University
Investigators
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Principal Investigator: Nada Alachkar, MD Johns Hopkins University
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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT04363502    
Other Study ID Numbers: IRB00247932
First Posted: April 27, 2020    Key Record Dates
Last Update Posted: May 19, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infection