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

NCT ID: NCT04409509

Last Updated: 2022-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-01
• Study Completion Date: 2021-01-12

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)

Conditions

Coronavirus Disease 2019 (COVID-19)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

CSL312

Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Group Type: EXPERIMENTAL

Garadacimab, Factor XIIa Antagonist Monoclonal Antibody

Intervention Type: BIOLOGICAL

Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Placebo

CSL312 diluent administered intravenously

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

CSL312 diluent administered intravenously

Interventions

Garadacimab, Factor XIIa Antagonist Monoclonal Antibody

Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Intervention Type: BIOLOGICAL

Placebo

CSL312 diluent administered intravenously

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CSL Behring

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

CSL Behring

Locations

Nova Clinical Research, LLC

Bradenton, Florida, United States

Theia Clinical Research, LLC

St. Petersburg, Florida, United States

MercyOne North Iowa Medical Center

Mason City, Iowa, United States

Northeast Iowa Medical Education Foundation

Waterloo, Iowa, United States

Lahey Hospital and Medical Center

Burlington, Massachusetts, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Holy Name Hospital

Teaneck, New Jersey, United States

Inspira Health Center Vineland

Vineland, New Jersey, United States

Sisters of Charity Hospital/ St. Joseph's Campus

Buffalo, New York, United States

Carolina Institute for Clinical Research

Fayetteville, North Carolina, United States

Monument Health Clinical Research

Rapid City, South Dakota, United States

PharmaTex Research

Amarillo, Texas, United States

UT Health Science Center, McGovern Medical School

Houston, Texas, United States

Inova Alexandria Hospital

Alexandria, Virginia, United States

Countries

United States

References

Papi A, Stapleton RD, Shore PM, Bica MA, Chen Y, Larbig M, Welte T. Efficacy and Safety of Garadacimab in Combination with Standard of Care Treatment in Patients with Severe COVID-19. Lung. 2023 Apr;201(2):159-170. doi: 10.1007/s00408-023-00615-9. Epub 2023 Mar 31.

Reference Type: DERIVED

PMID: 37000214 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CSL312_COVID-19

Identifier Type: -

Identifier Source: org_study_id