Clinical trial NCT04519424: CSL324 in COVID-19
Official title: A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate CSL324 in Coronavirus Disease 2019 (COVID-19)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Coronavirus Disease 2019 (COVID-19)
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2020-08-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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)

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