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

COVID-19 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: Terminated

Administrative data

• NCT number: NCT04381052
• Other study ID #: AAAT0142
• Status: Terminated
• Phase: Phase 2
• Start date: May 18, 2020
• Est. completion date: April 1, 2021

Study information

• Verified date: April 2022
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: April 1, 2021
• Est. primary completion date: April 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Clazakizumab
Dose is 25mg intravenously over 30 minutes.

Other:
• Placebo
Intravenously administered over 30 minutes.

Locations

Country	Name	City	State
United States	Columbia University Medical Center / New York Presbyerian Hospital	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Columbia University	CSL Behring, NYU Langone Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative Incidence of Serious Adverse Events Associated With Clazakizumab or Placebo		60 days
Secondary	Cumulative Incidence of Intubation		14 days
Secondary	Time to Extubation		14 days
Secondary	Length of Intensive Care Unit (ICU) Stay		14 days
Secondary	Number of Patients Who Present a Decrease in C-reactive Protein (CRP)		14 days
Secondary	Number of Patients With Acute Kidney Injury (AKI)		14 days
Secondary	Number of Patients With a Need for Renal Replacement Therapy (RRT)		14 days
Secondary	Duration of Renal Replacement Therapy (RRT)		60 days
Secondary	Patient Survival	Number of participants alive at day 28.	28 days
Secondary	Patient Survival	Number of participants alive at day 60, end of study.	60 days
Secondary	Number of Patients With Hemodialysis		60 days
Secondary	Number of Patients With Continuous Renal Replacement Therapies (CRRT)		60 days
Secondary	Number of Patients With Peritoneal Dialysis		60 days