Use of the Interleukin-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection

Covid19 Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04363502
• Other study ID #: IRB00247932
• Status: Recruiting
• Phase: Phase 2
• Start date: May 7, 2020
• Est. completion date: May 2022

Study information

• Verified date: June 2021
• Source: Johns Hopkins University
• Contact: Nada Alachkar, MD
• Phone: 4106149225
• Email: nalachk1[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: May 2022
• Est. primary completion date: May 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Covid19
• Infection

Intervention

Drug:
• Clazakizumab
The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes.
• Placebo
The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes.

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in C-reactive protein (CRP) level	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	Up to 3 days