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

Coronavirus Disease 2019 (COVID-19) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04409509
• Other study ID #: CSL312_COVID-19
• Status: Completed
• Phase: Phase 2
• Start date: July 1, 2020
• Est. completion date: January 12, 2021

Study information

• Verified date: January 2022
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: January 12, 2021
• Est. primary completion date: January 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronavirus Disease 2019 (COVID-19)
• Coronavirus Infections
• COVID-19

Intervention

Biological:
• Garadacimab, Factor XIIa Antagonist Monoclonal Antibody
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Drug:
• Placebo
CSL312 diluent administered intravenously

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation		From randomization to Day 28
Secondary	Percent of Participants With Death From All Causes		From randomization to Day 28
Secondary	Percent of Participants With Tracheal Intubation		From randomization to Day 28
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percent of Participants Requiring Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP)		From randomization to Day 28
Secondary	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
Secondary	Percent of Participants Requiring High-Flow Nasal Cannula (HFNC)		From randomization to Day 28
Secondary	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
Secondary	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
Secondary	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
Secondary	Length of Hospital Stay		From randomization to Day 28 (+/- 2 days)
Secondary	Number of Participants Experiencing Adverse Events (AEs)		Up to 28 days after CSL312 or placebo administration
Secondary	Percent of Participants Experiencing AEs		Up to 28 days after CSL312 or placebo administration
Secondary	Number of Participants Experiencing Serious Adverse Events (SAEs)		Up to 28 days after CSL312 or placebo administration
Secondary	Percent of Participants Experiencing SAEs		Up to 28 days after CSL312 or placebo administration
Secondary	Number of Participants With Adverse Events of Special Interest (AESIs)		Up to 28 days after CSL312 or placebo administration
Secondary	Percent of Participants With AESIs		Up to 28 days after CSL312 or placebo administration
Secondary	Number of Participants With Anti-CSL312 Antibodies		Up to 28 days after CSL312 or placebo administration
Secondary	Maximum Plasma Concentration (Cmax) of CSL312		Up to 28 days after CSL312 administration
Secondary	Time to Maximum Plasma Concentration (Tmax) of CSL312		Up to 28 days after CSL312 administration
Secondary	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
Secondary	Terminal Half-life (T1/2) of CSL312		Up to 28 days after CSL312 administration