Clinical trial NCT04409509: Treatment With CSL312 in Adults With Coronavirus Disease 2019 (COVID-19)
Official title: A Phase 2, Multicenter, Double Blind, Randomized, Placebo-Controlled Study to Evaluate CSL312 in Coronavirus Disease 2019 (COVID 19)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronavirus Disease 2019 (COVID-19)
Keywords: Prevention of respiratory failure
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2020-06-01
Enrollment: 124
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 prospective, phase 2, multicenter, randomized, double blind, placebo controlled, parallel group study to assess the safety and efficacy of CSL312 administered intravenously, in combination with standard of care (SOC) treatment, in patients with Coronavirus disease 2019 (COVID 19)


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection as determined using a molecular diagnostic test (reverse transcription polymerase chain reaction \[RT-PCR\] or equivalent) approved by regulatory authorities (including Food and Drug Administration or Brazilian Health Regulatory Agency) or allowed under an emergency use authorization within 14 days before Screening. If a false negative result is suspected, the SARS-CoV-2 test may be repeated within the Screening Period.
* Chest CT scan or X ray results confirming interstitial pneumonia
* Severe COVID 19 disease as evidenced by ≥ 1 of the following criteria at Screening including within 24 hours before Screening:

  * Respiratory frequency \> 30 breaths per minute
  * SpO2 ≤ 93% on room air
  * Ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) \< 300
  * Ratio of Arterial oxygen saturation to fraction of inspired oxygen (SaO2/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 IP, including expanded access or compassionate use with the only exception being administration of convalescent plasma. Administration of IP is permitted only if an emergency use authorization has been granted (eg, remdesivir). Additionally, off label use of approved drugs (eg, anti IL 6/anti IL 6R) is also permitted.
* Pregnant or breastfeeding (female subjects)
* Intubated and require mechanical ventilation (including ECMO) at the time of randomization
* In the opinion of the investigator, the subject is expected to be intubated in the first 24 hours after IMP administration
* Has a Do-Not-Intubate (DNI) or Do-Not-Resuscitate (DNR) order
* In the opinion of the investigator, not expected to survive for \> 48 hours after admission
* Presence of any of the following comorbid conditions prior to randomization and prior to SARS CoV 2 infection:

  * Severe heart failure (New York Heart Association Class IV)
  * End stage renal disease (Stage ≥ 4) or need for renal replacement therapy
  * Biopsy confirmed cirrhosis, portal hypertension, or hepatic encephalopathy
  * Malignancy (Stage IV)
  * Chronic lung disease requiring the use of oxygen at home
  * Active tuberculosis disease
* Active bleeding or a current clinically significant coagulopathy (eg, international normalized ratio \[INR\] \> 1.5) or clinically significant risk for bleeding (eg, recent intracranial hemorrhage or bleeding peptic ulcer within the last 4 weeks)
* History of venous thrombosis, myocardial infarction or cerebrovascular event within 3 months, or a prothrombotic disorder (eg, antithrombin III, protein C or protein S deficiency)
* Known or suspected Grade 3 or 4 infusion-related reaction or hypersensitivity (per Common Terminology Criteria for Adverse Events \[CTCAE\]) to monoclonal antibody therapy, or hypersensitivity to the IMP or any excipients of the IMP
* Currently receiving a therapy not permitted during the study.
* Female subject of childbearing potential or fertile male subject either not using or not willing to use an acceptable method of contraception to avoid pregnancy during the study and for 90 days after receipt of the last dose of IMP
* Any clinical or laboratory abnormality or other underlying conditions (eg, psychological disorders, substance abuse) that would render the subject unsuitable for participation in the study, in the opinion of the investigator

Primary outcomes:
measure: The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation
timeFrame: From randomization to Day 28
Secondary outcomes:
measure: Percent of Participants With Death From All Causes
timeFrame: From randomization to Day 28
measure: Percent of Participants With Tracheal Intubation
timeFrame: From randomization to Day 28
measure: Number of Participants With ≥ 2-Point Improvement Compared to Baseline on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Scale
timeFrame: From randomization to Day 28
measure: Percent of Participants With ≥ 2-Point Improvement Compared to Baseline on NIAID
timeFrame: From randomization to Day 28
measure: Number of Participants Within Each of the Categories of the NIAID at End of Study
timeFrame: Day 28
measure: Percent of Participants Within Each of the Categories of the NIAID at End of Study
timeFrame: Day 28
measure: Percent of Participants Requiring Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP)
timeFrame: From randomization to Day 28
measure: Percent of Participants Requiring Extracorporeal Membrane Oxygenation (ECMO)
timeFrame: From randomization to Day 28
measure: Percent of Participants Requiring High-Flow Nasal Cannula (HFNC)
timeFrame: From randomization to Day 28
measure: Maximum Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score
timeFrame: From randomization to Day 28
measure: Change From Baseline in SOFA Total Score
timeFrame: From randomization to Day 28
measure: Change From Baseline in the Individual Components of SOFA Score
timeFrame: From randomization to Day 28
measure: Length of Hospital Stay
timeFrame: From randomization to Day 28 (+/- 2 days)
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to 28 days after CSL312 or placebo administration
measure: Percent of Participants Experiencing AEs
timeFrame: Up to 28 days after CSL312 or placebo administration
measure: Number of Participants Experiencing Serious Adverse Events (SAEs)
timeFrame: Up to 28 days after CSL312 or placebo administration
measure: Percent of Participants Experiencing SAEs
timeFrame: Up to 28 days after CSL312 or placebo administration
measure: Number of Participants With Adverse Events of Special Interest (AESIs)
timeFrame: Up to 28 days after CSL312 or placebo administration
measure: Percent of Participants With AESIs
timeFrame: Up to 28 days after CSL312 or placebo administration
measure: Number of Participants With Anti-CSL312 Antibodies
timeFrame: Up to 28 days after CSL312 or placebo administration
measure: Maximum Plasma Concentration (Cmax) of CSL312
timeFrame: Up to 28 days after CSL312 administration
measure: Time to Maximum Plasma Concentration (Tmax) of CSL312
timeFrame: Up to 28 days after CSL312 administration
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-Last) of CSL312
timeFrame: Up to 28 days after CSL312 administration
measure: Terminal Half-life (T1/2) of CSL312
timeFrame: Up to 28 days after CSL312 administration
Other outcomes:
Locations:
city: Bradenton
country: United States
facility: Nova Clinical Research, LLC
state: Florida
city: Saint Petersburg
country: United States
facility: Theia Clinical Research, LLC
state: Florida
city: Mason City
country: United States
facility: MercyOne North Iowa Medical Center
state: Iowa
city: Waterloo
country: United States
facility: Northeast Iowa Medical Education Foundation
state: Iowa
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Teaneck
country: United States
facility: Holy Name Hospital
state: New Jersey
city: Vineland
country: United States
facility: Inspira Health Center Vineland
state: New Jersey
city: Buffalo
country: United States
facility: Sisters of Charity Hospital/ St. Joseph's Campus
state: New York
city: Fayetteville
country: United States
facility: Carolina Institute for Clinical Research
state: North Carolina
city: Rapid City
country: United States
facility: Monument Health Clinical Research
state: South Dakota
city: Amarillo
country: United States
facility: PharmaTex Research
state: Texas
city: Houston
country: United States
facility: UT Health Science Center, McGovern Medical School
state: Texas
city: Alexandria
country: United States
facility: Inova Alexandria Hospital
state: Virginia
Study officials:
affiliation: CSL Behring
name: Study Director
role: STUDY_DIRECTOR
References: