NCT04409509

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

Completed Phase 2 Results posted Last updated 24 January 2022

What this trial tests

Phase 2 trial testing Garadacimab, Factor XIIa Antagonist Monoclonal Antibody in Coronavirus Disease 2019 (COVID-19) in 124 participants. Completed in 12 January 2021.

Timeline

1 July 2020

Primary endpoint
12 January 2021

12 January 2021

Quick facts

Lead sponsor	CSL Behring
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	124
Start date	1 July 2020
Primary completion	12 January 2021
Estimated completion	12 January 2021
Sites	14 locations across United States

Drugs / interventions tested

• Garadacimab, Factor XIIa Antagonist Monoclonal Antibody — full drug profile →
• Placebo

Conditions studied

• Coronavirus Disease 2019 (COVID-19) — all drugs for Coronavirus Disease 2019 (COVID-19) →

Sponsor

CSL Behring — full company profile →

Who can join

18 and older, any sex, with Coronavirus Disease 2019 (COVID-19). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation Primary · From randomization to Day 28

Group	Value	95% CI
Placebo	26.2
CSL312	22.2

Percent of Participants With Death From All Causes Secondary · From randomization to Day 28

Group	Value	95% CI
Placebo	18.0
CSL312	17.5

Percent of Participants With Tracheal Intubation Secondary · From randomization to Day 28

Group	Value	95% CI
Placebo	24.6
CSL312	17.5

Number of Participants With ≥ 2-Point Improvement Compared to Baseline on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Scale Secondary · From randomization to Day 28

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, limitati

Group	Value	95% CI
Placebo	44
CSL312	42

Percent of Participants With ≥ 2-Point Improvement Compared to Baseline on NIAID Secondary · From randomization to Day 28

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, limitati

Group	Value	95% CI
Placebo	72.1
CSL312	66.7

Number of Participants Within Each of the Categories of the NIAID at End of Study Secondary · Day 28

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, limitati

Death

Group	Value	95% CI
Placebo	11
CSL312	11

Hospitalized, on Invasive Mechanical Ventilation or ECMO

Group	Value	95% CI
Placebo	2
CSL312	1

Hospitalized, on Non-invasive Ventilation or High-flow Oxygen Devices

Group	Value	95% CI
Placebo	2
CSL312	0

Hospitalized, Requiring Supplemental Oxygen

Group	Value	95% CI
Placebo	1
CSL312	2

Hospitalized, Not Requiring Supplemental Oxygen - Requiring Ongoing Medical Care

Group	Value	95% CI
Placebo	0
CSL312	0

Hospitalized, Not Requiring Supplemental Oxygen - no Longer Requiring Medical Care

Group	Value	95% CI
Placebo	0
CSL312	0

Not Hospitalized, Limitation on Activities and/or Requiring Home Oxygen

Group	Value	95% CI
Placebo	14
CSL312	11

Not Hospitalized, no Limitations on Activities

Group	Value	95% CI
Placebo	25
CSL312	26

Percent of Participants Within Each of the Categories of the NIAID at End of Study Secondary · Day 28

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, limitati

Death

Group	Value	95% CI
Placebo	18.0
CSL312	17.5

Hospitalized, on Invasive Mechanical Ventilation or ECMO

Group	Value	95% CI
Placebo	3.3
CSL312	1.6

Hospitalized, on Non-invasive Ventilation or High-flow Oxygen Devices

Group	Value	95% CI
Placebo	3.3
CSL312	0

Hospitalized, Requiring Supplemental Oxygen

Group	Value	95% CI
Placebo	1.6
CSL312	3.2

Hospitalized, Not Requiring Supplemental Oxygen - Requiring Ongoing Medical Care

Group	Value	95% CI
Placebo	0
CSL312	0

Hospitalized, Not Requiring Supplemental Oxygen - no Longer Requiring Medical Care

Group	Value	95% CI
Placebo	0
CSL312	0

Not Hospitalized, Limitation on Activities and/or Requiring Home Oxygen

Group	Value	95% CI
Placebo	23.0
CSL312	17.5

Not Hospitalized, no Limitations on Activities

Group	Value	95% CI
Placebo	41.0
CSL312	41.3

Percent of Participants Requiring Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP) Secondary · From randomization to Day 28

Group	Value	95% CI
Placebo	16.4
CSL312	19.0

Percent of Participants Requiring Extracorporeal Membrane Oxygenation (ECMO) Secondary · From randomization to Day 28

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.

Group	Value	95% CI
Placebo	0
CSL312	0

Percent of Participants Requiring High-Flow Nasal Cannula (HFNC) Secondary · From randomization to Day 28

Group	Value	95% CI
Placebo	18.0
CSL312	14.3

Maximum Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Secondary · From randomization to Day 28

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.

Group	Value	95% CI
Placebo	0.5	± 1.54
CSL312	0.1	± 0.79

Change From Baseline in SOFA Total Score Secondary · From randomization to Day 28

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.

Group	Value	95% CI
Placebo	-1.0	± 1.77
CSL312	-1.3	± 0.89

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 28 days per participant after CSL312 or placebo administration. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 19/59 (32%)

Deaths: 11/61

CSL312

Serious: 20/58 (34%)

Deaths: 11/63

Serious adverse events (38 terms)

Reaction	System	Placebo	CSL312
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—
Septic shock	Infections and infestations	—	—
Deep vein thrombosis	Vascular disorders	—	—
Hypotension	Vascular disorders	—	—
Cardiac arrest	Cardiac disorders	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—
Sepsis	Infections and infestations	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Pneumothorax	Respiratory, thoracic and mediastinal disorders	—	—
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Arterial thrombosis	Vascular disorders	—	—
Peripheral artery thrombosis	Vascular disorders	—	—
Peripheral ischaemia	Vascular disorders	—	—
Venous thrombosis	Vascular disorders	—	—
Pneumonia	Infections and infestations	—	—
Diverticulitis	Infections and infestations	—	—
Enterobacter bacteraemia	Infections and infestations	—	—
Enterobacter pneumonia	Infections and infestations	—	—
Pneumonia escherichia	Infections and infestations	—	—
Pneumonia streptococcal	Infections and infestations	—	—
Sinus tachycardia	Cardiac disorders	—	—

Other adverse events (13 terms — click to expand)

Reaction	System	Placebo	CSL312
Hypotension	Vascular disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Transaminases increased	Investigations	—	—
Hyperkalaemia	Metabolism and nutrition disorders	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Bradycardia	Cardiac disorders	—	—
Fibrin D dimer increased	Investigations	—	—
Septic shock	Infections and infestations	—	—
Anxiety	Psychiatric disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—

Most-reported serious reactions: Respiratory failure, Hypoxia, Acute respiratory failure, Septic shock, Deep vein thrombosis, Hypotension, Cardiac arrest, Pulmonary embolism.

Data from ClinicalTrials.gov NCT04409509 adverse events section.

Sponsor's own description

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)

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19.
   Bonaventura A, Vecchié A, Dagna L, Martinod K, et al · · 2021 · cited 738× · PMID 33824483 · DOI 10.1038/s41577-021-00536-9
2. An update to monoclonal antibody as therapeutic option against COVID-19.
   Deb P, Molla MMA, Saif-Ur-Rahman KM. · · 2021 · cited 91× · PMID 33585808 · DOI 10.1016/j.bsheal.2021.02.001
3. Defective NET clearance contributes to sustained FXII activation in COVID-19-associated pulmonary thrombo-inflammation.
   Englert H, Rangaswamy C, Deppermann C, Sperhake JP, et al · · 2021 · cited 76× · PMID 34000623 · DOI 10.1016/j.ebiom.2021.103382
4. Recent updates in the clinical trials of therapeutic monoclonal antibodies targeting cytokine storm for the management of COVID-19.
   Patel S, Saxena B, Mehta P. · · 2021 · cited 39× · PMID 33553708 · DOI 10.1016/j.heliyon.2021.e06158
5. Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants.
   Strohl WR, Ku Z, An Z, Carroll SF, et al · · 2022 · cited 31× · PMID 35476216 · DOI 10.1007/s40259-022-00529-7
6. Recent advances in antibody-based immunotherapy strategies for COVID-19.
   Esmaeilzadeh A, Rostami S, Yeganeh PM, Tahmasebi S, et al · · 2021 · cited 24× · PMID 34160093 · DOI 10.1002/jcb.30017
7. Therapeutic antibodies for COVID-19: is a new age of IgM, IgA and bispecific antibodies coming?
   Zhang J, Zhang H, Sun L. · · 2022 · cited 21× · PMID 35220888 · DOI 10.1080/19420862.2022.2031483
8. An update to "novel therapeutic approaches for treatment of COVID-19".
   Hossein-Khannazer N, Shokoohian B, Shpichka A, Aghdaei HA, et al · · 2021 · cited 21× · PMID 33392632 · DOI 10.1007/s00109-020-02027-1