Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04409509
Recruitment Status : Completed
First Posted : June 1, 2020
Last Update Posted : January 22, 2021
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Tracking Information
First Submitted Date  ICMJE May 28, 2020
First Posted Date  ICMJE June 1, 2020
Last Update Posted Date January 22, 2021
Actual Study Start Date  ICMJE July 1, 2020
Actual Primary Completion Date January 12, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2020)
The incidence of tracheal intubation or death prior to tracheal intubation [ Time Frame: From randomization to Day 28 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2020)
  • Proportion of subjects with death from all causes [ Time Frame: From randomization to Day 28 ]
  • Proportion of subjects intubated [ Time Frame: From randomization to Day 28 ]
  • Number and proportion of subjects with ≥ 2-point improvement on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal scale [ Time Frame: From randomization to Day 28 ]
  • Number and proportion of subjects within each of the categories of the NIAID [ Time Frame: From randomization to Day 28 ]
  • Proportion of subjects requiring continuous positive airway pressure (CPAP) [ Time Frame: From randomization to Day 28 ]
  • Proportion of subjects requiring bilevel positive airway pressure (BiPAP) [ Time Frame: From randomization to Day 28 ]
  • Proportion of subjects requiring high-flow nasal cannula (HFNC) [ Time Frame: From randomization to Day 28 ]
  • Proportion of subjects requiring extracorporeal membrane oxygenation (ECMO) [ Time Frame: From randomization to Day 28 ]
  • Maximum change from baseline in Sequential Organ Failure Assessment (SOFA) score [ Time Frame: From randomization to Day 28 ]
  • Change from Baseline in SOFA score and in the individual components of SOFA score [ Time Frame: From randomization to Day 28 ]
  • Length of hospital stay [ Time Frame: From randomization to Day 28 ]
  • Number and proportion of subjects experiencing Adverse Events (AEs) [ Time Frame: Up to 28 days after CSL312 or placebo administration ]
  • Number and proportion of subjects experiencing serious adverse events (SAEs) [ Time Frame: Up to 28 days after CSL312 or placebo administration ]
  • Number and proportion of subjects with adverse events of special interest (AESIs) [ Time Frame: Up to 28 days after CSL312 or placebo administration ]
  • Number and proportion of subjects with CSL312 induced anti-CSL312 antibodies [ Time Frame: Up to 28 days after CSL312 or placebo administration ]
  • Maximum plasma concentration (Cmax) of CSL312 [ Time Frame: Up to 28 days after CSL312 administration ]
  • Time to maximum plasma concentration (Tmax) of CSL312 [ Time Frame: 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 [ Time Frame: Up to 28 days after CSL312 administration ]
  • Terminal half-life (T1/2) of CSL312 [ Time Frame: Up to 28 days after CSL312 administration ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2020)
  • Proportion of subjects with death from all causes [ Time Frame: From randomization to Day 28 ]
  • Proportion of subjects intubated [ Time Frame: From randomization to Day 28 ]
  • Number and proportion of subjects with ≥ 2-point improvement on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal scale [ Time Frame: From randomization to Day 28 ]
  • Number and proportion of subjects within each of the categories of the NIAID [ Time Frame: From randomization to Day 28 ]
  • Proportion of subjects requiring continuous positive airway pressure (CPAP) [ Time Frame: From randomization to Day 28 ]
  • Proportion of subjects requiring bilevel positive airway pressure (BiPAP) [ Time Frame: From randomization to Day 28 ]
  • Proportion of subjects requiring high-flow nasal cannula (HFNC) [ Time Frame: From randomization to Day 28 ]
  • Proportion of subjects requiring extracorporeal membrane oxygenation (ECMO) [ Time Frame: From randomization to Day 28 ]
  • Maximum change from baseline in Sequential Organ Failure Assessment (SOFA) score [ Time Frame: From randomization to Day 28 ]
  • Average SOFA score over the subject's duration of the study [ Time Frame: From randomization to Day 28 ]
  • Length of hospital stay [ Time Frame: From randomization to Day 28 ]
  • Number and proportion of subjects experiencing Adverse Events (AEs) [ Time Frame: Up to 28 days after CSL312 or placebo administration ]
  • Number and proportion of subjects experiencing serious adverse events (SAEs) [ Time Frame: Up to 28 days after CSL312 or placebo administration ]
  • Number and proportion of subjects with adverse events of special interest (AESIs) [ Time Frame: Up to 28 days after CSL312 or placebo administration ]
  • Number and proportion of subjects with CSL312 induced anti-CSL312 antibodies [ Time Frame: Up to 28 days after CSL312 or placebo administration ]
  • Maximum plasma concentration (Cmax) of CSL312 [ Time Frame: Up to 28 days after CSL312 administration ]
  • Time to maximum plasma concentration (Tmax) of CSL312 [ Time Frame: Up to 28 days after CSL312 administration ]
  • Area under the plasma concentration-time curve (AUC) of CSL312 [ Time Frame: Up to 28 days after CSL312 administration ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treatment With CSL312 in Adults With Coronavirus Disease 2019 (COVID-19)
Official Title  ICMJE A Phase 2, Multicenter, Double Blind, Randomized, Placebo-Controlled Study to Evaluate CSL312 in Coronavirus Disease 2019 (COVID 19)
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)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Coronavirus Disease 2019 (COVID-19)
Intervention  ICMJE
  • Biological: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody
    Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
  • Drug: Placebo
    CSL312 diluent administered intravenously
Study Arms  ICMJE
  • Experimental: CSL312
    Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
    Intervention: Biological: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody
  • Placebo Comparator: Placebo
    CSL312 diluent administered intravenously
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 28, 2020)
124
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 12, 2021
Actual Primary Completion Date January 12, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04409509
Other Study ID Numbers  ICMJE CSL312_COVID-19
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.

Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
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.
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.

Responsible Party CSL Behring
Study Sponsor  ICMJE CSL Behring
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Study Director CSL Behring
PRS Account CSL Behring
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP