Clazakizumab (Anti-Interleukin 6 (IL-6) Monoclonal) Compared to Placebo for Coronavirus Disease 2019 (COVID-19)

A Phase II Trial to Evaluate the Safety and Tolerability of Clazakizumab® (Anti-IL-6 Monoclonal) Compared to Placebo for the Treatment of COVID-19 Infection

This is a single center, randomized, double-blind, placebo-controlled, exploratory phase II study enrolling 60 patients. We propose the administration of a blinded dose of an investigational product (IP) (clazakizumab or placebo [0.9% saline]) in patients with COVID-19 disease and signs of pulmonary involvement who have not yet required mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO). If a patient progresses to mechanical ventilation and/or ECMO or develops clinical signs of deteriorating COVID-19 disease, and there are no treatment related serious adverse events (SAEs), within the initial 14 day period after the first dose of the IP, at the discretion of the investigator or treating physician, open-label clazakizumab 25mg IV x 1 dose may be administered. A minimum of 24 hours should elapse between the first dose of IP and this dose of open-label clazakizumab. The patient will remain blinded as to the identity of the IP administered in the first dose.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Clazakizumab

Detailed Description

Patients admitted to the hospital with COVID-19 disease with signs of pulmonary involvement will be randomized to receive the anti-IL-6 drug clazakizumab 25mg IV or placebo. Patients will be followed for improvements in clinical symptoms and laboratory parameters which are part of our COVID-19 lab panel described below. Patients will receive standard of care (SOC) supportive treatment and will be followed for 14 days. If a patient from either group progresses to the need for mechanical ventilation and/or ECMO, or develops clinical signs of deteriorating COVID-19 disease, and there are no serious treatment related SAEs, at the discretion of the investigator or treating physician, the patient may receive a single dose of open-label clazakizumab 25mg IV. A minimum of 24 hours should elapse between the first dose of IP and this dose of open-label clazakizumab.

Enrolled patients will receive clazakizumab 25 mg or placebo (0.9% saline) given by IV infusion over 30 minutes. Clazakizumab will be administered in 50 mL of 0.9% saline on Day 1. COVID-19 lab panel and clinical parameters will be monitored to determine if patients are progressing towards need for ventilation and/or ECMO. The parameters below will be monitored and patient status will be assessed by the clinical team.

If patients do develop these criteria, open-label clazakizumab 25 mg IV may be administered as discussed above. A minimum of 24 hours should elapse between the first dose of IP and this dose of open-label clazakizumab. Patients ventilated with or without ECMO will continue to be monitored post-treatment for signs of improvement, (i.e., decreasing FiO2 requirements, chest X-ray (CXR) improvements, C-reactive protein (CRP) reductions, extubation and discharge home) or death.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >18 at the time of screening
• Subject must be able to understand and provide informed consent
• Hospitalized with COVID-19 (+) disease (confirmed by polymerase chain reaction (PCR) assay from any specimen (e.g. respiratory, blood, urine, stool, other bodily fluid))
• Not on mechanical ventilation and/or ECMO

• Evidence of pulmonary involvement with at least 2 of the following:

  1. Oxygen saturation (SpO2) at rest in ambient air with SpO2 ≤ 94%
  2. Tachypnea with resting respiration rate > 25 breaths/minute
  3. Partial pressure of oxygen (PaO2) / fraction of inspired oxygen (FiO2) ≤ 300 mmHg
  4. Chest imaging (radiograph, CT scan, or lung ultrasound) with abnormalities consistent COVID-19 pneumonia
  5. C-reactive protein (CRP) >35 mg/L

Exclusion Criteria:

• Previous hypersensitivity or allergic reactions to clazakizumab
• Lactating or pregnant females
• Subjects with latent Tuberculosis (TB) and who are not receiving treatment
• Subjects with active TB
• A significantly abnormal general serum screening lab result defined as a White Blood Count (WBC) < 3.0 X 103/ml, a Hgb < 8.0 g/dL, a platelet count < 50 X 103/ml, a serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) > 5x upper limit normal
• Participation in another clinical trial investigating COVID-19 aimed agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clazakizumab; 25 mg in 50 mL of 0.9% saline given by IV infusion x 1 dose over 30 minutes	Drug: Clazakizumab; IV Infusion
Placebo Comparator: Placebo; 50 mL of 0.9% saline given by IV infusion x 1 dose over 30 minutes	Drug: Clazakizumab; IV Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Clazakizumab for the Treatment of Patients With COVID-19 Disease	Number of severe adverse events (SAEs) that are unusual, unexpected, or assessed as related to the investigational product (IP)	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Survival at 28 Days	Number of patients alive at 28 days	28 days
Patient Survival at 60 Days	Number of patients alive at 60 days	60 days
Number of Patients Requiring the Dose of Open-label Clazakizumab	Number of patients requiring the dose of open-label clazakizumab	14 days
Number of Days in Intensive Care Unit (ICU)	Number of days in ICU compared to placebo	60 days
Number of Days in Hospital	Number of days in hospital compared to placebo	60 days
Number of Patients Requiring Mechanical Ventilation and/or Extracorporeal Membrane Oxygenation (ECMO)	Number of patients requiring mechanical ventilation and/or ECMO at 14 days after the first administered dose in comparison to placebo	14 days

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2020
• Primary Completion (Actual): September 30, 2020
• Study Completion (Actual): September 30, 2020

Study Registration Dates

• First Submitted: April 13, 2020
• First Submitted That Met QC Criteria: April 13, 2020
• First Posted (Actual): April 16, 2020

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 00000644

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No