CSL324 in COVID-19

Study Overview
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Brief Summary
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This is a phase 2, prospective, multicenter, randomized, double blind, placebo controlled, parallel group study to evaluate the safety and efficacy of intravenous (IV) administration of CSL324, administered in combination with SOC treatment, in subjects with COVID 19. For the purposes of this study, standard of care (SOC) may include any written or established treatment protocol followed at the study site for the treatment of severe COVID-19 or its complications, including off-label use of marketed pharmaceutical products and / or products with emergency use authorization granted for the treatment of COVID-19 (ie, not yet marketed) (eg, remdesivir).

Official Title
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A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate CSL324 in Coronavirus Disease 2019 (COVID-19)

Conditions
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Coronavirus Disease 2019 (COVID-19)

Intervention / Treatment
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* Biological: CSL324
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years at the time informed consent is obtained Positive for SARS-CoV-2 infection determined by a diagnostic test approved by the Food and Drug Administration (FDA) or allowed under an emergency use authorization Chest computed tomography (CT) scan or X ray results confirming interstitial pneumonia Meets ≥ 1 of the following criteria (subjects improving while on respiratory support still qualify): Respiratory rate > 30 breaths per minute Peripheral (capillary) oxygen saturation (SpO2) ≤ 93% on room air Partial pressure of oxygen in arterial blood (PaO2) to fraction of inspired oxygen (FiO2) ratio (PaO2 / FiO2) < 300 SpO2 / FiO2 ratio < 218 (if PaO2 / FiO2 ratio is not available) Radiographic lung infiltrates > 50% Exclusion Criteria: Currently enrolled, planning to enroll, or participated, within the last 30 days, in a clinical study requiring administration of an investigational product (ie, not yet marketed), including expanded access or compassionate use Exceptions: Administration of investigational product with emergency use authorization granted for treatment of COVID 19 (eg, remdesivir) is permitted Convalescent plasma as part of approved special access programs such as expanded access, emergency IND, or compassionate use is permitted Pregnant or breastfeeding (female subjects) Intubated and requires mechanical ventilation (including ECMO) at time of randomization Exception: use of HFNC oxygen and noninvasive ventilation are permitted Endotracheal intubation is imminent, in the opinion of the investigator Not expected to survive for more than 48 hours after hospital admission, in the opinion of the investigator Presence of any of the following comorbid conditions before randomization and prior to SARS-CoV-2 infection: New York Heart Association class IV heart failure Stage 4 or 5 chronic kidney disease or requires renal replacement therapy Biopsy proven cirrhosis, portal hypertension or hepatic encephalopathy Stage IV malignancy Chronic lung disease requiring home oxygen Active tuberculosis History or evidence of pulmonary alveolar proteinosis Confirmed diagnosis or clinical suspicion of bacterial pneumonia or active uncontrolled bacterial, fungal, or non SARS-CoV-2 viral infection at Screening Absolute neutrophil count (ANC) value < 5 × 109 cells/L at Screening (can be lowered up to < 1.5 × 109 cells/L after Independent Data Monitoring Committee review of safety data, if CSL324 induced neutropenia is not assessed as a safety concern) Currently receiving a prohibited therapy including G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF), or antibody against interleukin 6 (IL-6) / IL 6 receptor (anti IL-6 / 6R)

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CSL324<br>CSL324 administered intravenously | Biological: CSL324<br>* Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody<br>|
| Placebo Comparator: Placebo<br>Normal saline administered intravenously | Drug: Placebo<br>* Normal saline (0.9% sodium chloride)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects progressing to endotracheal intubation or death prior to endotracheal intubation |  | Randomization to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of deaths from all causes |  | Randomization to Day 28 | 
| Proportion of subjects intubated |  | Randomization to Day 28 | 
| Median length of stay in hospital |  | Randomization to Day 28 | 
| Number and proportion of subjects with at least a 2-point improvement in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale |  | Randomization to Day 28 | 
| Number and proportion of subjects within each of the categories of the NIAID ordinal scale |  | Daily up to Day 28 | 
| Proportion of subjects using continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) |  | Randomization to Day 28 | 
| Proportion of subjects using high-flow nasal cannula (HFNC) |  | Randomization to Day 28 | 
| Proportion of subjects using extracorporeal membrane oxygenation (ECMO) |  | Randomization to Day 28 | 
| Maximum Change in Sequential Organ Failure Assessment (SOFA) score |  | Randomization to Day 28 | 
| Change in SOFA score and in individual components of the SOFA score |  | Baseline to Day 28 | 
| Number and proportion of subjects experiencing adverse events (AEs) |  | Up to 60 days | 
| Number and proportion of subjects experiencing serious adverse events (SAEs) |  | Up to 60 days | 
| Number and proportion of subjects experiencing adverse events of special interest (AESIs) |  | Up to 60 days | 
| Presence of anti-CSL324 antibodies |  | Up to 28 days | 
| Maximum concentration (Cmax) of CSL324 |  | Up to 28 days | 
| Time to reach maximum concentration (Tmax) of CSL324 |  | Up to 28 days | 
| Area under the concentration-time curve (AUC0-last) of CSL324 |  | Up to 28 days | 
| Trough concentration (Ctrough) of CSL324 |  | Before dose on Day 4 and Day 8 |