Treatment With CSL312 in Adults With Coronavirus Disease 2019 (COVID-19)

A Phase 2, Multicenter, Double Blind, Randomized, Placebo-Controlled Study to Evaluate CSL312 in Coronavirus Disease 2019 (COVID 19)

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)

Study Overview

• Status: Completed
• Conditions: Coronavirus Disease 2019 (COVID-19)
• Intervention / Treatment: Biological: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Bradenton, Florida, United States, 34209
      • Nova Clinical Research, LLC
    • Saint Petersburg, Florida, United States, 33707
      • Theia Clinical Research, LLC
  • Iowa
    • Mason City, Iowa, United States, 50401
      • MercyOne North Iowa Medical Center
    • Waterloo, Iowa, United States, 50702
      • Northeast Iowa Medical Education Foundation
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Hospital
    • Vineland, New Jersey, United States, 08360
      • Inspira Health Center Vineland
  • New York
    • Buffalo, New York, United States, 14225
      • Sisters of Charity Hospital/ St. Joseph's Campus
  • North Carolina
    • Fayetteville, North Carolina, United States, 28304
      • Carolina Institute for Clinical Research
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Monument Health Clinical Research
  • Texas
    • Amarillo, Texas, United States, 79109
      • PharmaTex Research
    • Houston, Texas, United States, 77030
      • UT Health Science Center, McGovern Medical School
  • Virginia
    • Alexandria, Virginia, United States, 22304
      • Inova Alexandria Hospital

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
• 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

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: CSL312; Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously	Biological: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody; Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Placebo Comparator: Placebo; CSL312 diluent administered intravenously	Drug: Placebo; CSL312 diluent administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation	From randomization to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants With Death From All Causes		From randomization to Day 28
Percent of Participants With Tracheal Intubation		From randomization to Day 28
Number of Participants With ≥ 2-Point Improvement Compared to Baseline on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Scale	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.	From randomization to Day 28
Percent of Participants With ≥ 2-Point Improvement Compared to Baseline on NIAID	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.	From randomization to Day 28
Number of Participants Within Each of the Categories of the NIAID at End of Study	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.	Day 28
Percent of Participants Within Each of the Categories of the NIAID at End of Study	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.	Day 28
Percent of Participants Requiring Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP)		From randomization to Day 28
Percent of Participants Requiring Extracorporeal Membrane Oxygenation (ECMO)	None of the enrolled subjects required the use of ECMO during their participation in this study. Therefore, no data to report for this outcome measure.	From randomization to Day 28
Percent of Participants Requiring High-Flow Nasal Cannula (HFNC)		From randomization to Day 28
Maximum Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score	The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.	From randomization to Day 28
Change From Baseline in SOFA Total Score	The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.	From randomization to Day 28
Change From Baseline in the Individual Components of SOFA Score	The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.	From randomization to Day 28
Length of Hospital Stay		From randomization to Day 28 (+/- 2 days)
Number of Participants Experiencing Adverse Events (AEs)		Up to 28 days after CSL312 or placebo administration
Percent of Participants Experiencing AEs		Up to 28 days after CSL312 or placebo administration
Number of Participants Experiencing Serious Adverse Events (SAEs)		Up to 28 days after CSL312 or placebo administration
Percent of Participants Experiencing SAEs		Up to 28 days after CSL312 or placebo administration
Number of Participants With Adverse Events of Special Interest (AESIs)		Up to 28 days after CSL312 or placebo administration
Percent of Participants With AESIs		Up to 28 days after CSL312 or placebo administration
Number of Participants With Anti-CSL312 Antibodies		Up to 28 days after CSL312 or placebo administration
Maximum Plasma Concentration (Cmax) of CSL312		Up to 28 days after CSL312 administration
Time to Maximum Plasma Concentration (Tmax) of CSL312		Up to 28 days after CSL312 administration
Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-Last) of CSL312		Up to 28 days after CSL312 administration
Terminal Half-life (T1/2) of CSL312		Up to 28 days after CSL312 administration

Collaborators and Investigators

• Sponsor: CSL Behring

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): January 12, 2021
• Study Completion (Actual): January 12, 2021

Study Registration Dates

• First Submitted: May 28, 2020
• First Submitted That Met QC Criteria: May 28, 2020
• First Posted (Actual): June 1, 2020

Study Record Updates

• Last Update Posted (Actual): January 24, 2022
• Last Update Submitted That Met QC Criteria: January 20, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Prevention of respiratory failure
• 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; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: CSL312_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