CSL324 in COVID-19

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

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).

Study Overview

• Status: Withdrawn
• Conditions: Coronavirus Disease 2019 (COVID-19)
• Intervention / Treatment: Biological: CSL324; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

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

Description

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)

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
Experimental: CSL324; CSL324 administered intravenously	Biological: CSL324; Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody
Placebo Comparator: Placebo; Normal saline administered intravenously	Drug: Placebo; Normal saline (0.9% sodium chloride)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: CSL Behring

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): April 1, 2021
• Study Completion (Anticipated): May 1, 2021

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: August 18, 2020
• First Posted (Actual): August 19, 2020

Study Record Updates

• Last Update Posted (Actual): October 14, 2020
• Last Update Submitted That Met QC Criteria: October 12, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections
• Other Study ID Numbers: CSL324_COVID-19

Plan for Individual participant data (IPD)

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

IPD Plan Description

CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

• IPD Sharing Time Frame: IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.

IPD Sharing Access Criteria

Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.

An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.

The requesting party must execute an appropriate data sharing agreement before IPD will be made available.

• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

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