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

Phase 2

Completed

Conditions: COVID-19

Interventions: Drug: Clazakizumab

Registration Number: NCT04348500

Lead Sponsor: Cedars-Sinai Medical Center

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 17

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Clazakizumab	50 mL of 0.9% saline given by IV infusion x 1 dose over 30 minutes
Clazakizumab	Clazakizumab	25 mg in 50 mL of 0.9% saline given by IV infusion x 1 dose over 30 minutes

Primary Outcome Measures

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

Secondary Outcome Measures

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