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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Clazakizumab


Participation Criteria
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Eligibility Criteria
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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: Oxygen saturation (SpO2) at rest in ambient air with SpO2 ≤ 94% Tachypnea with resting respiration rate > 25 breaths/minute Partial pressure of oxygen (PaO2) / fraction of inspired oxygen (FiO2) ≤ 300 mmHg Chest imaging (radiograph, CT scan, or lung ultrasound) with abnormalities consistent COVID-19 pneumonia 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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 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.
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |