NCT04324021

Efficacy and Safety of Emapalumab and Anakinra in Reducing Hyperinflammation and Respiratory Distress in Patients With COVID-19 Infection.

Terminated Phase 2, PHASE3 Results posted Last updated 10 March 2022

What this trial tests

Phase 2, PHASE3 trial testing Emapalumab in SARS-CoV-2 in 16 participants. Terminated before completion.

Timeline

2 April 2020

Primary endpoint
13 November 2020

13 November 2020

Quick facts

Lead sponsor	Swedish Orphan Biovitrum
Phase	Phase 2, PHASE3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	16
Start date	2 April 2020
Primary completion	13 November 2020
Estimated completion	13 November 2020
Sites	12 locations across Italy, United States

Drugs / interventions tested

• Emapalumab (EMAPALUMAB) — full drug profile →
• Anakinra (ANAKINRA) — full drug profile →

Conditions studied

• SARS-CoV-2 — all drugs for SARS-CoV-2 →

Sponsor

Swedish Orphan Biovitrum — full company profile →

Who can join

Adults 18 to 85, any sex, with SARS-CoV-2. 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.

Number of Participants With Treatment Success Primary · Up to Day 15

Defined as the number of patients not requiring invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO)

Group	Value	95% CI
Emapalumab	3
Anakinra	4
Standard of Care	5

Number of Participants Requiring Mechanical Ventilation Secondary · Date of randomization to date of mechanical ventilation, up to 15 Days

Measured in number of participants

Group	Value	95% CI
Emapalumab	1
Anakinra	1
Standard of Care	1

Change From Baseline in Modified Early Warning System Score Secondary · Baseline, Day 15

The full (unabbreviated) scale name is Modified Early Warning system score (MEWS score) Measured in total score Total score is the sum of 5 categorized components (blood pressure, heart rate, respiratory rate, temperature and alert/voice/pain/unresponsive score) that are assigned a score between 0 and 2 or 0 and 3. MEWS total score range is 0 to 14. Higher score= worse outcome

Group	Value	95% CI
Emapalumab	-1.00	± 0.00
Anakinra	0.00	± 0.82
Standard of Care	-0.75	± 0.96

Change From Baseline in Ferritin Secondary · Baseline, Days 4, 7, 10, 13 and 15

Measured in local units

Change from Baseline at D4

Group	Value	95% CI
Emapalumab	-380.8	± 3026.3
Anakinra	-2864.2	± 3789.3
Standard of Care	-770.2	± 1093.0

Change from Baselind at D7

Group	Value	95% CI
Emapalumab	60.5	± 2503.4
Anakinra	-2179.6	± 3108.3
Standard of Care	-1103.3	± 168.4

Change from Baselind at D10

Group	Value	95% CI
Emapalumab	-527.5	± 3086.3
Anakinra	-2066.8	± 3342.9
Standard of Care	-1295.0	± 359.8

Change from Baseline at D13

Group	Value	95% CI
Emapalumab	-823.1	± 2792.5
Anakinra	-1931.1	± 3601.8
Standard of Care	-1260.6	± 781.7

Change from baseline at D15

Group	Value	95% CI
Emapalumab	-506.6	± 2518.2
Anakinra	-2045.2	± 3627.7
Standard of Care	-842.6	± 1020.0

Change From Baseline in Lactate Dehydrogenase (LDH) Secondary · Baseline, Days 4, 7, 10, 13 and 15

Measured in local units

Change from Baseline at D4

Group	Value	95% CI
Emapalumab	-128.3	± 160.9
Anakinra	-31.8	± 13.0
Standard of Care	-70.4	± 85.5

Change from Baseline at D7

Group	Value	95% CI
Emapalumab	-164.3	± 267.4
Anakinra	-16.8	± 162.9
Standard of Care	-96.0	± 107.3

Change from Baseline at D10

Group	Value	95% CI
Emapalumab	-184.3	± 200.2
Anakinra	-60.4	± 76.4
Standard of Care	-143.5	± 128.7

Change from Baseline at D13

Group	Value	95% CI
Emapalumab	-185.3	± 260.9
Anakinra	-2.6	± 264.4
Standard of Care	-155.0	± 121.0

Change from Baseline at D15

Group	Value	95% CI
Emapalumab	-163.6	± 252.4
Anakinra	-20.6	± 274.8
Standard of Care	-158.4	± 108.3

Change From Baseline in D-dimers Secondary · Baseline, Days 4, 7, 10, 13 and 15

Measured in local units

Change from Baseline at D4

Group	Value	95% CI
Emapalumab	-0.19	± 0.34
Anakinra	5.13	± 14.73
Standard of Care	-2.05	± 1.65

Change from Baseline at D7

Group	Value	95% CI
Emapalumab	-7.37	± 13.84
Anakinra	6.78	± 19.41
Standard of Care	-4.30	± 1.96

Change from Baseline at D10

Group	Value	95% CI
Emapalumab	-10.07	± 18.16
Anakinra	4.66	± 12.82
Standard of Care	-7.18	± 5.96

Change from Baseline at D13

Group	Value	95% CI
Emapalumab	-7.99	± 13.40
Anakinra	6.84	± 19.39
Standard of Care	-5.67	± 7.11

Change from Baseline at D15

Group	Value	95% CI
Emapalumab	-6.84	± 12.67
Anakinra	6.64	± 19.51
Standard of Care	-5.55	± 6.45

Change From Baseline in Resting Peripheral Capillary Oxygen Saturation (SpO2) Secondary · Baseline, 3 assessments every Days 4, 7, 10, 13 and 15

Measured in percent (%)

Change from baseline at D4

Group	Value	95% CI
Emapalumab	-0.667	± 3.598
Anakinra	0.267	± 2.060
Standard of Care	0.722	± 2.603

Change from baseline at D7

Group	Value	95% CI
Emapalumab	0.867	± 2.923
Anakinra	0.667	± 1.748
Standard of Care	2.000	± 2.415

Change from baseline at D10

Group	Value	95% CI
Emapalumab	0.625	± 3.523
Anakinra	0.267	± 1.754
Standard of Care	2.333	± 3.528

Change from baseline at D13

Group	Value	95% CI
Emapalumab	1.358	± 2.140
Anakinra	-2.233	± 6.098
Standard of Care	1.600	± 3.639

Change from baseline at D15

Group	Value	95% CI
Emapalumab	-1.640	± 3.383
Anakinra	-2.400	± 5.771
Standard of Care	2.944	± 2.840

Change From Baseline in Oxygen Supplementation Secondary · Baseline, Days 4, 7, 10, 13 and 15.

Measured in l/min

Change from baseline at D4

Group	Value	95% CI
Emapalumab	0.0	± 0.0
Anakinra	2.8	± 5.5
Standard of Care	-0.2	± 9.5

Change from baseline at D7

Group	Value	95% CI
Emapalumab	-1.0	± 5.8
Anakinra	-1.8	± 4.8
Standard of Care	-7.8	± 9.1

Change from baseline at D10

Group	Value	95% CI
Emapalumab	-3.3	± 6.9
Anakinra	-2.3	± 6.2
Standard of Care	-17.8	± 18.2

Change from baseline at D13

Group	Value	95% CI
Emapalumab	-4.3	± 8.1
Anakinra	-3.3	± 7.8
Standard of Care	-20.0	± 17.0

Change from baseline at D15

Group	Value	95% CI
Emapalumab	-3.6	± 9.3
Anakinra	-4.3	± 7.9
Standard of Care	-15.3	± 19.3

Change From Baseline in Partial Pressure of Oxygen/Fraction of Inspired Oxygen (PaO2/FiO2) Secondary · Baseline, Day 15

Measured in mmHg

Group	Value	95% CI
Emapalumab	28.98	± 106.66
Anakinra	51.19
Standard of Care	156.72	± 113.53

Number of Participants With Changes in High-resolution Computed Tomography (CT) Scan of the Chest Secondary · Screening, Day 15

Measured in scan evaluation: Normal, Abnormal but not clinically significant, Abnormal clinical significant, Not Done

Group	Value	95% CI
Emapalumab	0
Anakinra	0
Standard of Care	1
Emapalumab	1
Anakinra	3
Standard of Care	1
Emapalumab	3
Anakinra	1
Standard of Care	2

Overall Survival Secondary · Weeks 6 and 10

Confirmation of death

Group	Value	95% CI
Emapalumab	2
Anakinra	1
Standard of Care	0

Number of Patients With Hospital Discharge Secondary · Until discharge up to Week 10

Measured in number of patients

Group	Value	95% CI
Emapalumab	3
Anakinra	4
Standard of Care	5
Emapalumab	2
Anakinra	1
Standard of Care	1

Adverse events — posted to ClinicalTrials.gov

Time frame: All fatal and life-threatening SAEs occurring after study drug initiation and up to the end of study visit (Visit 9, Week 10) were reported. All adverse event data were collected from Day 1 to follow-up Week 10.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Emapalumab

Serious: 2/5 (40%)

Deaths: 2/5

Anakinra

Serious: 1/5 (20%)

Deaths: 1/5

Standard of Care

Serious: 0/6 (0%)

Deaths: 0/6

Serious adverse events (2 terms)

Reaction	System	Emapalumab	Anakinra	Standard of Care
End-stage respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—

Other adverse events (4 terms — click to expand)

Reaction	System	Emapalumab	Anakinra	Standard of Care
Atrial Fibrillation	Cardiac disorders	—	—	—
Muscle Hematoma	Musculoskeletal and connective tissue disorders	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—
Hypertransaminasaemia	Hepatobiliary disorders	—	—	—

Most-reported serious reactions: End-stage respiratory failure, Respiratory failure.

Data from ClinicalTrials.gov NCT04324021 adverse events section.

Sponsor's own description

Hyper-inflammation, caused by a cytokine storm resulting from an exaggerated response of the immune system in the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is considered to represent one of the most important negative prognostic factors in patients infected with sSARS-CoV-2. The objective of this study is to investigate new treatment options to reduce the number of patients requiring mechanical ventilation. This is intended to address the most urgent need to preserve the access to intensive care unit support to the lowest possible number of patients and may potentially reduce mortality.

Publications & conference data

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

1. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages.
   Merad M, Martin JC. · · 2020 · cited 1909× · PMID 32376901 · DOI 10.1038/s41577-020-0331-4
2. Targeting potential drivers of COVID-19: Neutrophil extracellular traps.
   Barnes BJ, Adrover JM, Baxter-Stoltzfus A, Borczuk A, et al · · 2020 · cited 1151× · PMID 32302401 · DOI 10.1084/jem.20200652
3. Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy.
   George PM, Wells AU, Jenkins RG. · · 2020 · cited 794× · PMID 32422178 · DOI 10.1016/s2213-2600(20)30225-3
4. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study.
   Cavalli G, De Luca G, Campochiaro C, Della-Torre E, et al · · 2020 · cited 711× · PMID 32501454 · DOI 10.1016/s2665-9913(20)30127-2
5. Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts.
   Wang J, Jiang M, Chen X, Montaner LJ. · · 2020 · cited 551× · PMID 32534467 · DOI 10.1002/jlb.3covr0520-272r
6. Large-Scale Multi-omic Analysis of COVID-19 Severity.
   Overmyer KA, Shishkova E, Miller IJ, Balnis J, et al · · 2021 · cited 510× · PMID 33096026 · DOI 10.1016/j.cels.2020.10.003
7. On the Alert for Cytokine Storm: Immunopathology in COVID-19.
   Henderson LA, Canna SW, Schulert GS, Volpi S, et al · · 2020 · cited 487× · PMID 32293098 · DOI 10.1002/art.41285
8. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions.
   Jamilloux Y, Henry T, Belot A, Viel S, et al · · 2020 · cited 486× · PMID 32376392 · DOI 10.1016/j.autrev.2020.102567