Trial Outcomes & Findings for Efficacy and Safety of Emapalumab and Anakinra in Reducing Hyperinflammation and Respiratory Distress in Patients With COVID-19 Infection. (NCT NCT04324021)

NCT ID: NCT04324021

Last Updated: 2022-03-10

Results Overview

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

• Recruitment status: TERMINATED
• Study phase: PHASE2/PHASE3
• Target enrollment: 16 participants
• Primary outcome timeframe: Up to Day 15
• Results posted on: 2022-03-10

Participant Flow

Patients were screened within 72h prior to the first IMP administration. A total of 54 patients were planned to be randomized. A total of 16 patients were randomized and analyzed.

Participant milestones

Measure	Emapalumab Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care Standard of care according to local practice
Overall Study STARTED	5	5	6
Overall Study COMPLETED	3	4	5
Overall Study NOT COMPLETED	2	1	1

Reasons for withdrawal

Measure	Emapalumab Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care Standard of care according to local practice
Overall Study Adverse Event	1	0	0
Overall Study Lack of Efficacy	0	0	1
Overall Study Death	1	1	0

Baseline Characteristics

Data not available for the whole population

Baseline characteristics by cohort

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice	Total n=16 Participants Total of all reporting groups
Age, Continuous	65.0 years STANDARD_DEVIATION 14.8 • n=5 Participants	62.4 years STANDARD_DEVIATION 11.1 • n=5 Participants	62.5 years STANDARD_DEVIATION 62.5 • n=6 Participants	63.3 years STANDARD_DEVIATION 12.3 • n=16 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=5 Participants	0 Participants n=6 Participants	2 Participants n=16 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=5 Participants	6 Participants n=6 Participants	14 Participants n=16 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=5 Participants	0 Participants n=6 Participants	2 Participants n=16 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=5 Participants	5 Participants n=6 Participants	12 Participants n=16 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=5 Participants	1 Participants n=6 Participants	2 Participants n=16 Participants
Region of Enrollment Italy	5 participants n=5 Participants	5 participants n=5 Participants	6 participants n=6 Participants	16 participants n=16 Participants
Hospitalization	5 Participants n=5 Participants	5 Participants n=5 Participants	6 Participants n=6 Participants	16 Participants n=16 Participants
Height (cm)	170.8 cm STANDARD_DEVIATION 10.9 • n=5 Participants • Data not available for the whole population	170.2 cm STANDARD_DEVIATION 4.4 • n=5 Participants • Data not available for the whole population	172.3 cm STANDARD_DEVIATION 14.4 • n=4 Participants • Data not available for the whole population	171 cm STANDARD_DEVIATION 9.5 • n=14 Participants • Data not available for the whole population
Weight (kg)	77.4 kg STANDARD_DEVIATION 15.0 • n=5 Participants • Data not available for the whole population	79.4 kg STANDARD_DEVIATION 13.4 • n=5 Participants • Data not available for the whole population	83.0 kg STANDARD_DEVIATION 12.8 • n=4 Participants • Data not available for the whole population	79.7 kg STANDARD_DEVIATION 13 • n=14 Participants • Data not available for the whole population
Symptom duration (days)	4.0 days STANDARD_DEVIATION 4.2 • n=5 Participants	1.0 days STANDARD_DEVIATION 0 • n=5 Participants	5.3 days STANDARD_DEVIATION 4.8 • n=6 Participants	3.6 days STANDARD_DEVIATION 4.0 • n=16 Participants
Oxygen levels (mmHg)	103.0 mmHg STANDARD_DEVIATION 38.2 • n=4 Participants • Data not available for the whole population	78.5 mmHg STANDARD_DEVIATION 21.0 • n=4 Participants • Data not available for the whole population	78.6 mmHg STANDARD_DEVIATION 20.5 • n=5 Participants • Data not available for the whole population	85.2 mmHg STANDARD_DEVIATION 27.7 • n=13 Participants • Data not available for the whole population
Fraction of Inspired oxygen (FiO2) (%)	61.8 % of inspired oxygen STANDARD_DEVIATION 29.9 • n=4 Participants • Data not available for the whole population	54.8 % of inspired oxygen STANDARD_DEVIATION 37.1 • n=4 Participants • Data not available for the whole population	53.2 % of inspired oxygen STANDARD_DEVIATION 22.4 • n=5 Participants • Data not available for the whole population	56.3 % of inspired oxygen STANDARD_DEVIATION 27.4 • n=13 Participants • Data not available for the whole population

PRIMARY outcome

Timeframe: Up to Day 15

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

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Number of Participants With Treatment Success	3 Participants	4 Participants	5 Participants

SECONDARY outcome

Timeframe: Date of randomization to date of mechanical ventilation, up to 15 Days

Measured in number of participants

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Number of Participants Requiring Mechanical Ventilation	1 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change From Baseline in Modified Early Warning System Score	-1.00 scores on a scale Standard Deviation 0.00	0.00 scores on a scale Standard Deviation 0.82	-0.75 scores on a scale Standard Deviation 0.96

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change From Baseline in Ferritin Change from Baseline at D4	-380.8 pmol/L Standard Deviation 3026.3	-2864.2 pmol/L Standard Deviation 3789.3	-770.2 pmol/L Standard Deviation 1093.0
Change From Baseline in Ferritin Change from Baselind at D7	60.5 pmol/L Standard Deviation 2503.4	-2179.6 pmol/L Standard Deviation 3108.3	-1103.3 pmol/L Standard Deviation 168.4
Change From Baseline in Ferritin Change from Baselind at D10	-527.5 pmol/L Standard Deviation 3086.3	-2066.8 pmol/L Standard Deviation 3342.9	-1295.0 pmol/L Standard Deviation 359.8
Change From Baseline in Ferritin Change from Baseline at D13	-823.1 pmol/L Standard Deviation 2792.5	-1931.1 pmol/L Standard Deviation 3601.8	-1260.6 pmol/L Standard Deviation 781.7
Change From Baseline in Ferritin Change from baseline at D15	-506.6 pmol/L Standard Deviation 2518.2	-2045.2 pmol/L Standard Deviation 3627.7	-842.6 pmol/L Standard Deviation 1020.0

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change From Baseline in Lactate Dehydrogenase (LDH) Change from Baseline at D4	-128.3 U/L Standard Deviation 160.9	-31.8 U/L Standard Deviation 13.0	-70.4 U/L Standard Deviation 85.5
Change From Baseline in Lactate Dehydrogenase (LDH) Change from Baseline at D7	-164.3 U/L Standard Deviation 267.4	-16.8 U/L Standard Deviation 162.9	-96.0 U/L Standard Deviation 107.3
Change From Baseline in Lactate Dehydrogenase (LDH) Change from Baseline at D10	-184.3 U/L Standard Deviation 200.2	-60.4 U/L Standard Deviation 76.4	-143.5 U/L Standard Deviation 128.7
Change From Baseline in Lactate Dehydrogenase (LDH) Change from Baseline at D13	-185.3 U/L Standard Deviation 260.9	-2.6 U/L Standard Deviation 264.4	-155.0 U/L Standard Deviation 121.0
Change From Baseline in Lactate Dehydrogenase (LDH) Change from Baseline at D15	-163.6 U/L Standard Deviation 252.4	-20.6 U/L Standard Deviation 274.8	-158.4 U/L Standard Deviation 108.3

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change From Baseline in D-dimers Change from Baseline at D4	-0.19 nmol/L Standard Deviation 0.34	5.13 nmol/L Standard Deviation 14.73	-2.05 nmol/L Standard Deviation 1.65
Change From Baseline in D-dimers Change from Baseline at D7	-7.37 nmol/L Standard Deviation 13.84	6.78 nmol/L Standard Deviation 19.41	-4.30 nmol/L Standard Deviation 1.96
Change From Baseline in D-dimers Change from Baseline at D10	-10.07 nmol/L Standard Deviation 18.16	4.66 nmol/L Standard Deviation 12.82	-7.18 nmol/L Standard Deviation 5.96
Change From Baseline in D-dimers Change from Baseline at D13	-7.99 nmol/L Standard Deviation 13.40	6.84 nmol/L Standard Deviation 19.39	-5.67 nmol/L Standard Deviation 7.11
Change From Baseline in D-dimers Change from Baseline at D15	-6.84 nmol/L Standard Deviation 12.67	6.64 nmol/L Standard Deviation 19.51	-5.55 nmol/L Standard Deviation 6.45

SECONDARY outcome

Timeframe: Baseline, 3 assessments every Days 4, 7, 10, 13 and 15

Population: Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints

Measured in percent (%)

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change From Baseline in Resting Peripheral Capillary Oxygen Saturation (SpO2) Change from baseline at D4	-0.667 SpO2% Standard Deviation 3.598	0.267 SpO2% Standard Deviation 2.060	0.722 SpO2% Standard Deviation 2.603
Change From Baseline in Resting Peripheral Capillary Oxygen Saturation (SpO2) Change from baseline at D7	0.867 SpO2% Standard Deviation 2.923	0.667 SpO2% Standard Deviation 1.748	2.000 SpO2% Standard Deviation 2.415
Change From Baseline in Resting Peripheral Capillary Oxygen Saturation (SpO2) Change from baseline at D10	0.625 SpO2% Standard Deviation 3.523	0.267 SpO2% Standard Deviation 1.754	2.333 SpO2% Standard Deviation 3.528
Change From Baseline in Resting Peripheral Capillary Oxygen Saturation (SpO2) Change from baseline at D13	1.358 SpO2% Standard Deviation 2.140	-2.233 SpO2% Standard Deviation 6.098	1.600 SpO2% Standard Deviation 3.639
Change From Baseline in Resting Peripheral Capillary Oxygen Saturation (SpO2) Change from baseline at D15	-1.640 SpO2% Standard Deviation 3.383	-2.400 SpO2% Standard Deviation 5.771	2.944 SpO2% Standard Deviation 2.840

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15.

Population: Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints

Measured in l/min

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=4 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change From Baseline in Oxygen Supplementation Change from baseline at D4	0.0 L/min Standard Deviation 0.0	2.8 L/min Standard Deviation 5.5	-0.2 L/min Standard Deviation 9.5
Change From Baseline in Oxygen Supplementation Change from baseline at D7	-1.0 L/min Standard Deviation 5.8	-1.8 L/min Standard Deviation 4.8	-7.8 L/min Standard Deviation 9.1
Change From Baseline in Oxygen Supplementation Change from baseline at D10	-3.3 L/min Standard Deviation 6.9	-2.3 L/min Standard Deviation 6.2	-17.8 L/min Standard Deviation 18.2
Change From Baseline in Oxygen Supplementation Change from baseline at D13	-4.3 L/min Standard Deviation 8.1	-3.3 L/min Standard Deviation 7.8	-20.0 L/min Standard Deviation 17.0
Change From Baseline in Oxygen Supplementation Change from baseline at D15	-3.6 L/min Standard Deviation 9.3	-4.3 L/min Standard Deviation 7.9	-15.3 L/min Standard Deviation 19.3

SECONDARY outcome

Timeframe: Baseline, Day 15

Population: Change from baseline at Day 15 Data not available for the whole population

Measured in mmHg

Outcome measures

Measure	Emapalumab n=2 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=1 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=4 Participants Standard of care according to local practice
Change From Baseline in Partial Pressure of Oxygen/Fraction of Inspired Oxygen (PaO2/FiO2)	28.98 mmHg Standard Deviation 106.66	51.19 mmHg	156.72 mmHg Standard Deviation 113.53

SECONDARY outcome

Timeframe: Screening, Day 15

Population: Data not available for all patients

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

Outcome measures

Measure	Emapalumab n=4 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=4 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=4 Participants Standard of care according to local practice
Number of Participants With Changes in High-resolution Computed Tomography (CT) Scan of the Chest Normal	0 Participants	0 Participants	1 Participants
Number of Participants With Changes in High-resolution Computed Tomography (CT) Scan of the Chest Abnormal (NC)	1 Participants	3 Participants	1 Participants
Number of Participants With Changes in High-resolution Computed Tomography (CT) Scan of the Chest Abnormal (CS)	3 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Weeks 6 and 10

Confirmation of death

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Overall Survival	2 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Until discharge up to Week 10

Population: Hospital discharge

Measured in number of patients

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Number of Patients With Hospital Discharge Hospital Discharge	3 Participants	4 Participants	5 Participants
Number of Patients With Hospital Discharge Terminated prior to discharge	2 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change of Carbon Dioxide Tension (pCO2) in Hemogasanalysis From Baseline Change from baseline at D4	0.00 mmHg Standard Deviation 7.21	-1.00 mmHg Standard Deviation 3.46	2.00 mmHg Standard Deviation 5.77
Change of Carbon Dioxide Tension (pCO2) in Hemogasanalysis From Baseline Change from baseline at D7	-0.33 mmHg Standard Deviation 9.45	1.00 mmHg Standard Deviation 1.41	5.46 mmHg Standard Deviation 5.68
Change of Carbon Dioxide Tension (pCO2) in Hemogasanalysis From Baseline Change from baseline at D10	2.33 mmHg Standard Deviation 6.03	3.67 mmHg Standard Deviation 8.08	4.20 mmHg Standard Deviation 5.12
Change of Carbon Dioxide Tension (pCO2) in Hemogasanalysis From Baseline Change from baseline at D13	0.30 mmHg Standard Deviation 9.48	6.50 mmHg Standard Deviation 3.54	0.25 mmHg Standard Deviation 4.11
Change of Carbon Dioxide Tension (pCO2) in Hemogasanalysis From Baseline Change from baseline at D15	0.77 mmHg Standard Deviation 8.33	3.75 mmHg Standard Deviation 5.74	4.00 mmHg Standard Deviation 5.10

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change of Oxygen Tension (pO2) in Hemogasanalysis From Baseline Change from baseline at D4	19.33 mmHg Standard Deviation 44.28	40.67 mmHg Standard Deviation 34.78	5.75 mmHg Standard Deviation 16.92
Change of Oxygen Tension (pO2) in Hemogasanalysis From Baseline Change from baseline at D7	19.33 mmHg Standard Deviation 36.56	18.50 mmHg Standard Deviation 13.44	23.64 mmHg Standard Deviation 35.04
Change of Oxygen Tension (pO2) in Hemogasanalysis From Baseline Change from baseline at D10	4.00 mmHg Standard Deviation 37.36	-1.33 mmHg Standard Deviation 11.93	4.00 mmHg Standard Deviation 43.73
Change of Oxygen Tension (pO2) in Hemogasanalysis From Baseline Change from baseline at D13	18.00 mmHg Standard Deviation 84.85	-12.00 mmHg Standard Deviation 5.66	24.25 mmHg Standard Deviation 36.04
Change of Oxygen Tension (pO2) in Hemogasanalysis From Baseline Change from baseline at D15	17.57 mmHg Standard Deviation 61.05	8.75 mmHg Standard Deviation 47.84	8.80 mmHg Standard Deviation 21.37

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change of Potassium in Hemogasanalysis From Baseline Change from baseline at D4	0.55 mmol/L Standard Deviation 0.92	-0.35 mmol/L Standard Deviation 0.49	0.45 mmol/L Standard Deviation 1.34
Change of Potassium in Hemogasanalysis From Baseline Change from baseline at D7	0.45 mmol/L Standard Deviation 1.20	0.40 mmol/L	0.53 mmol/L Standard Deviation 0.93
Change of Potassium in Hemogasanalysis From Baseline Change from baseline at D10	0.25 mmol/L Standard Deviation 0.92	0.25 mmol/L Standard Deviation 0.49	0.43 mmol/L Standard Deviation 1.22
Change of Potassium in Hemogasanalysis From Baseline Change from baseline at D13	-0.50 mmol/L	0.10 mmol/L	0.10 mmol/L Standard Deviation 0.85
Change of Potassium in Hemogasanalysis From Baseline Change from baseline at D15	0.00 mmol/L Standard Deviation 0.71	0.03 mmol/L Standard Deviation 0.75	0.17 mmol/L Standard Deviation 0.47

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change of Sodium in Hemogasanalysis From Baseline Change from baseline at D4	3.0 mmol/L Standard Deviation 5.7	-0.5 mmol/L Standard Deviation 2.1	-4.5 mmol/L Standard Deviation 2.1
Change of Sodium in Hemogasanalysis From Baseline Change from baseline at D7	1.0 mmol/L Standard Deviation 1.4	-5.0 mmol/L	0.3 mmol/L Standard Deviation 4.0
Change of Sodium in Hemogasanalysis From Baseline Change from baseline at D10	2.0 mmol/L Standard Deviation 4.2	-3.0 mmol/L Standard Deviation 7.1	1.3 mmol/L Standard Deviation 1.2
Change of Sodium in Hemogasanalysis From Baseline Change from baseline at D13	-2.0 mmol/L	-6.0 mmol/L	-1.0 mmol/L Standard Deviation 1.4
Change of Sodium in Hemogasanalysis From Baseline Change from Baseline at D15	2.5 mmol/L Standard Deviation 6.4	0.0 mmol/L Standard Deviation 2.6	0.7 mmol/L Standard Deviation 2.1

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change of Chloride in Hemogasanalysis From Baseline Change from baseline at D4	2.0 mmol/L Standard Deviation 5.7	-0.5 mmol/L Standard Deviation 2.1	1.5 mmol/L Standard Deviation 2.1
Change of Chloride in Hemogasanalysis From Baseline Change from baseline at D7	0.5 mmol/L Standard Deviation 0.7	-4.0 mmol/L	2.5 mmol/L Standard Deviation 0.7
Change of Chloride in Hemogasanalysis From Baseline Change from baseline at D10	0.0 mmol/L Standard Deviation 2.8	-4.5 mmol/L Standard Deviation 3.5	4.0 mmol/L Standard Deviation 1.4
Change of Chloride in Hemogasanalysis From Baseline Change from baseline at D13	-1.0 mmol/L	-4.0 mmol/L	3.0 mmol/L
Change of Chloride in Hemogasanalysis From Baseline Change from baseline at D15	2.0 mmol/L Standard Deviation 4.2	-2.0 mmol/L Standard Deviation 3.0	3.0 mmol/L Standard Deviation 2.8

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change of Lactic Acid in Hemogasanalysis From Baseline Change from baseline at D4	0.20 mmol/L	0.00 mmol/L Standard Deviation 0.28	-0.45 mmol/L Standard Deviation 1.20
Change of Lactic Acid in Hemogasanalysis From Baseline Change from baseline at D7	0.70 mmol/L	1.80 mmol/L	0.00 mmol/L Standard Deviation 0.85
Change of Lactic Acid in Hemogasanalysis From Baseline Change from baseline at D10	0.90 mmol/L	1.20 mmol/L Standard Deviation 0.17	-0.50 mmol/L Standard Deviation 0.28
Change of Lactic Acid in Hemogasanalysis From Baseline Change from baseline at D13	—	0.10 mmol/L	0.20 mmol/L
Change of Lactic Acid in Hemogasanalysis From Baseline Change from baseline at D15	0.00 mmol/L	1.27 mmol/L Standard Deviation 1.16	-0.05 mmol/L Standard Deviation 0.07

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change of Hemoglobin in Hemogasanalysis From Baseline Change from baseline at D4	-34.0 g/L Standard Deviation 46.7	-15.5 g/L Standard Deviation 10.6	8.0 g/L Standard Deviation 2.8
Change of Hemoglobin in Hemogasanalysis From Baseline Change from baseline at D7	-41.0 g/L Standard Deviation 65.1	3.0 g/L	6.7 g/L Standard Deviation 1.5
Change of Hemoglobin in Hemogasanalysis From Baseline Change from baseline at D10	-34.0 g/L Standard Deviation 62.2	7.5 g/L Standard Deviation 6.4	-1.7 g/L Standard Deviation 9.5
Change of Hemoglobin in Hemogasanalysis From Baseline Change from baseline at D13	-73.0 g/L	2.0 g/L	-6.5 g/L Standard Deviation 20.5
Change of Hemoglobin in Hemogasanalysis From Baseline Change from baseline at D15	-38.0 g/L Standard Deviation 49.5	-3.0 g/L Standard Deviation 18.0	-4.0 g/L Standard Deviation 15.9

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change From Baseline in White Blood Cells With Differential Counts Change from baseline at D4	1.000 10^9 cells /L Standard Deviation 4.408	0.294 10^9 cells /L Standard Deviation 0.886	0.332 10^9 cells /L Standard Deviation 3.009
Change From Baseline in White Blood Cells With Differential Counts Change from baseline at D7	0.340 10^9 cells /L Standard Deviation 2.623	2.812 10^9 cells /L Standard Deviation 2.953	1.738 10^9 cells /L Standard Deviation 4.165
Change From Baseline in White Blood Cells With Differential Counts Change from baseline at D10	2.728 10^9 cells /L Standard Deviation 1.867	4.796 10^9 cells /L Standard Deviation 3.091	0.806 10^9 cells /L Standard Deviation 3.643
Change From Baseline in White Blood Cells With Differential Counts Change from baseline at D13	1.548 10^9 cells /L Standard Deviation 5.265	1.588 10^9 cells /L Standard Deviation 2.653	-0.318 10^9 cells /L Standard Deviation 4.079
Change From Baseline in White Blood Cells With Differential Counts Change from baseline at D15	1.686 10^9 cells /L Standard Deviation 4.395	1.070 10^9 cells /L Standard Deviation 2.420	1.878 10^9 cells /L Standard Deviation 4.788

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change From Baseline in Red Blood Counts Change from baseline at D4	-0.260 10^12 cells/L Standard Deviation 0.470	-0.022 10^12 cells/L Standard Deviation 0.351	-0.108 10^12 cells/L Standard Deviation 0.359
Change From Baseline in Red Blood Counts Change from baseline at D7	-0.385 10^12 cells/L Standard Deviation 0.732	0.016 10^12 cells/L Standard Deviation 0.422	-0.196 10^12 cells/L Standard Deviation 0.465
Change From Baseline in Red Blood Counts Change from baseline at D10	-0.415 10^12 cells/L Standard Deviation 0.875	0.220 10^12 cells/L Standard Deviation 0.435	-0.262 10^12 cells/L Standard Deviation 0.549
Change From Baseline in Red Blood Counts Change from baseline at D13	-0.350 10^12 cells/L Standard Deviation 1.254	0.106 10^12 cells/L Standard Deviation 0.395	-0.275 10^12 cells/L Standard Deviation 0.564
Change From Baseline in Red Blood Counts Change from baseline at D15	-0.510 10^12 cells/L Standard Deviation 0.969	0.004 10^12 cells/L Standard Deviation 0.531	-0.163 10^12 cells/L Standard Deviation 0.571

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change From Baseline in Hemoglobin Change from baseline at D4	-6.2 g/L Standard Deviation 14.6	0.8 g/L Standard Deviation 7.0	-3.5 g/L Standard Deviation 9.1
Change From Baseline in Hemoglobin Change from baseline at D7	-9.3 g/L Standard Deviation 21.3	0.8 g/L Standard Deviation 13.1	-6.2 g/L Standard Deviation 10.7
Change From Baseline in Hemoglobin Change from baseline at D10	-11.3 g/L Standard Deviation 24.5	6.6 g/L Standard Deviation 11.9	-8.0 g/L Standard Deviation 16.0
Change From Baseline in Hemoglobin Change from baseline at D13	-10.8 g/L Standard Deviation 36.8	2.8 g/L Standard Deviation 13.6	-8.2 g/L Standard Deviation 17.3
Change From Baseline in Hemoglobin Change from baseline at D15	-14.0 g/L Standard Deviation 28.8	0.00 g/L Standard Deviation 15.6	-3.7 g/L Standard Deviation 16.9

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Day 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change From Baseline in Platelet Count Change from baseline at D4	29.0 10^9 cells /L Standard Deviation 77.2	85.4 10^9 cells /L Standard Deviation 76.7	9.8 10^9 cells /L Standard Deviation 153.7
Change From Baseline in Platelet Count Change from baseline at D7	19.8 10^9 cells /L Standard Deviation 116.6	140.4 10^9 cells /L Standard Deviation 191.8	47.4 10^9 cells /L Standard Deviation 232.9
Change From Baseline in Platelet Count Change from baseline at D10	-3.8 10^9 cells /L Standard Deviation 142.5	129.8 10^9 cells /L Standard Deviation 223.9	9.0 10^9 cells /L Standard Deviation 232.8
Change From Baseline in Platelet Count Change from baseline at D13	-32.0 10^9 cells /L Standard Deviation 126.5	80.8 10^9 cells /L Standard Deviation 213.2	-53.8 10^9 cells /L Standard Deviation 191.9
Change From Baseline in Platelet Count Change from baseline at D15	-37.6 10^9 cells /L Standard Deviation 129.0	41.2 10^9 cells /L Standard Deviation 169.3	-67.2 10^9 cells /L Standard Deviation 158.1

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change From Baseline in Fibrinogen Change from baseline at D7	-3.925 umol/L Standard Deviation 6.113	-4.898 umol/L Standard Deviation 2.610	-1.147 umol/L Standard Deviation 7.883
Change From Baseline in Fibrinogen Change from baseline at D4	-1.435 umol/L Standard Deviation 3.137	-2.434 umol/L Standard Deviation 1.830	-0.088 umol/L Standard Deviation 4.582
Change From Baseline in Fibrinogen Change from baseline at D10	-3.535 umol/L Standard Deviation 8.998	-4.980 umol/L Standard Deviation 2.625	-5.562 umol/L Standard Deviation 5.089
Change From Baseline in Fibrinogen Change from baseline at D13	-2.587 umol/L Standard Deviation 9.308	-6.227 umol/L Standard Deviation 2.627	-5.479 umol/L Standard Deviation 5.027
Change From Baseline in Fibrinogen Change from baseline at D15	-0.588 umol/L Standard Deviation 9.210	-6.380 umol/L Standard Deviation 2.357	-4.596 umol/L Standard Deviation 5.624

SECONDARY outcome

Timeframe: Day 15

Population: Change from baseline at Day 15

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change From Baseline in Complement Factors C3/C4 C3	0.054 g/L Standard Deviation 0.094	-0.068 g/L Standard Deviation 0.222	-0.020 g/L Standard Deviation 0.581
Change From Baseline in Complement Factors C3/C4 C4	0.024 g/L Standard Deviation 0.043	-0.108 g/L Standard Deviation 0.080	-0.007 g/L Standard Deviation 0.192

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Day 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=4 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=2 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=2 Participants Standard of care according to local practice
Change From Baseline in Prothrombin Time Change from baseline at D7	-1.250 sec Standard Deviation 0.071	0.300 sec Standard Deviation 0.283	-2.100 sec
Change From Baseline in Prothrombin Time Change from baseline at D4	-0.867 sec Standard Deviation 0.058	0750 sec Standard Deviation 0.071	-0.550 sec Standard Deviation 1.344
Change From Baseline in Prothrombin Time Change from Baseline at D10	-1.003 sec Standard Deviation 0.895	-0.150 sec Standard Deviation 0.919	-1.700 sec
Change From Baseline in Prothrombin Time Change from Baseline at D13	-2.250 sec Standard Deviation 0.354	0.050 sec Standard Deviation 0.495	-1.600 sec
Change From Baseline in Prothrombin Time Change from baseline at D15	-1.278 sec Standard Deviation 1.087	-0.150 sec Standard Deviation 0.778	-0.800 sec Standard Deviation 1.697

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Day 15 Data not available for the whole population

Measured in local units

Outcome measures

Measure	Emapalumab n=1 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=2 Participants Standard of care according to local practice
Change From Baseline in Cardiac Troponin Change from Baseline at D4	-0.017 ug/L	—	0.002 ug/L Standard Deviation 0.002
Change From Baseline in Cardiac Troponin Change from Baseline at D7	-0.022 ug/L	—	0.001 ug/L Standard Deviation 0.001
Change From Baseline in Cardiac Troponin Change from Baseline at D10	-0.022 ug/L	—	-0.001 ug/L Standard Deviation 0.001
Change From Baseline in Cardiac Troponin Change from Baseline at D13	-0.021 ug/L	—	-0.001 ug/L Standard Deviation 0.001
Change From Baseline in Cardiac Troponin Change from Baseline at D15	-0.022 ug/L	—	-0.001 ug/L Standard Deviation 0.001

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Day 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change From Baseline in Aspartate Aminotransferase (AST) Change from baseline at D4	-46.0 U/L Standard Deviation 79.8	-19.2 U/L Standard Deviation 32.0	-63.2 U/L Standard Deviation 146.0
Change From Baseline in Aspartate Aminotransferase (AST) Change from Baseline at D7	-52.8 U/L Standard Deviation 107.0	-27.6 U/L Standard Deviation 36.8	-65.4 U/L Standard Deviation 171.1
Change From Baseline in Aspartate Aminotransferase (AST) Change from Baseline at D10	-53.3 U/L Standard Deviation 108.6	-27.8 U/L Standard Deviation 32.9	-79.8 U/L Standard Deviation 170.6
Change From Baseline in Aspartate Aminotransferase (AST) Change from Baseline at D13	-44.0 U/L Standard Deviation 119.3	-25.2 U/L Standard Deviation 28.9	-83.6 U/L Standard Deviation 163.2
Change From Baseline in Aspartate Aminotransferase (AST) Change from baseline at D15	-35.4 U/L Standard Deviation 105.3	-25.8 U/L Standard Deviation 28.3	-77.7 U/L Standard Deviation 151.0

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Day 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change From Baseline in Alanine Aminotransferase (ALT) Change from Baseline D4	-74.8 U/L Standard Deviation 152.9	2.6 U/L Standard Deviation 38.8	-23.6 U/L Standard Deviation 148.8
Change From Baseline in Alanine Aminotransferase (ALT) Change from Baseline D7	-97.5 U/L Standard Deviation 237.1	16.6 U/L Standard Deviation 66.9	-62.0 U/L Standard Deviation 251.3
Change From Baseline in Alanine Aminotransferase (ALT) Change from Baseline D10	-107.8 U/L Standard Deviation 258.3	5.0 U/L Standard Deviation 54.5	-107.0 U/L Standard Deviation 350.0
Change From Baseline in Alanine Aminotransferase (ALT) Change from Baseline D13	-111.0 U/L Standard Deviation 293.3	-4.8 U/L Standard Deviation 51.9	-119.2 U/L Standard Deviation 352.2
Change From Baseline in Alanine Aminotransferase (ALT) Change from Baseline at D15	-90.6 U/L Standard Deviation 260.7	-5.8 U/L Standard Deviation 53.2	-121.8 U/L Standard Deviation 309.1

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Day 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change From Baseline in Total Bilirubin Levels Change from Baseline at D4	-0.171 umol/L Standard Deviation 3.519	-1.129 umol/L Standard Deviation 12.314	0.376 umol/L Standard Deviation 2.600
Change From Baseline in Total Bilirubin Levels Change from Baseline D7	-1.496 umol/L Standard Deviation 4.011	-0.376 umol/L Standard Deviation 15.492	0.684 umol/L Standard Deviation 9.922
Change From Baseline in Total Bilirubin Levels Change from Baseline D10	-0.385 umol/L Standard Deviation 4.598	4.685 umol/L Standard Deviation 21.108	0.787 umol/L Standard Deviation 11.931
Change From Baseline in Total Bilirubin Levels Change from Baseline D13	-1.710 umol/L Standard Deviation 4.413	13.885 umol/L Standard Deviation 30.276	3.591 umol/L Standard Deviation 14.146
Change From Baseline in Total Bilirubin Levels Change from Baseline at D15	-3.523 umol/L Standard Deviation 4.473	14.125 umol/L Standard Deviation 29.771	-0.057 umol/L Standard Deviation 9.046

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Day 15. Data not available for the whole population

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change From Baseline in C-Reactive Protein Change from Baseline D4	-53.73 mg/L Standard Deviation 98.88	-20.66 mg/L Standard Deviation 22.29	-12.65 mg/L Standard Deviation 12.81
Change From Baseline in C-Reactive Protein Change from Baseline D7	-63.65 mg/L Standard Deviation 101.74	-19.20 mg/L Standard Deviation 30.95	-10.98 mg/L Standard Deviation 19.57
Change From Baseline in C-Reactive Protein Change from Baseline D10	-60.05 mg/L Standard Deviation 106.21	-20.70 mg/L Standard Deviation 30.57	-14.60 mg/L Standard Deviation 15.72
Change From Baseline in C-Reactive Protein Change from Baseline D13	-60.50 mg/L Standard Deviation 106.66	-8.26 mg/L Standard Deviation 50.51	-16.33 mg/L Standard Deviation 14.27
Change From Baseline in C-Reactive Protein Change from Baseline D15	-38.96 mg/L Standard Deviation 103.48	-8.32 mg/L Standard Deviation 50.53	-15.26 mg/L Standard Deviation 12.71

SECONDARY outcome

Timeframe: Baseline, Days 4, 7, 10, 13 and 15

Population: Change from baseline at Day 15 Data not available for all patients at all timepoints

Measured in local units

Outcome measures

Measure	Emapalumab n=5 Participants Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 Participants Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 Participants Standard of care according to local practice
Change From Baseline in Creatinine Change from Baseline D4	-6.542 umol/L Standard Deviation 9.430	1.414 umol/L Standard Deviation 8.516	-6.041 umol/L Standard Deviation 8.148
Change From Baseline in Creatinine Change from Baseline D7	-8.840 umol/L Standard Deviation 14.454	0.530 umol/L Standard Deviation 6.893	0.000 umol/L Standard Deviation 6.156
Change From Baseline in Creatinine Change from Baseline D10	-7.514 umol/L Standard Deviation 14.481	0.000 umol/L Standard Deviation 5.830	-0.530 umol/L Standard Deviation 5.506
Change From Baseline in Creatinine Change from Baseline D13	-5.304 umol/L Standard Deviation 20.171	0.000 umol/L Standard Deviation 8.928	-1.945 umol/L Standard Deviation 3.088
Change From Baseline in Creatinine Change from Baseline D15	-9.901 umol/L Standard Deviation 19.281	-0.354 umol/L Standard Deviation 9.756	-5.746 umol/L Standard Deviation 24.292

Adverse Events

Emapalumab

Serious events: 2 serious events

Other events: 1 other events

Deaths: 2 deaths

Anakinra

Serious events: 1 serious events

Other events: 1 other events

Deaths: 1 deaths

Standard of Care

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Emapalumab n=5 participants at risk Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 participants at risk Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 participants at risk Standard of care according to local practice
Respiratory, thoracic and mediastinal disorders End-stage respiratory failure	40.0% 2/5 • Number of events 2 • 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.	0.00% 0/5 • 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.	0.00% 0/6 • 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.
Respiratory, thoracic and mediastinal disorders Respiratory failure	20.0% 1/5 • Number of events 1 • 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.	20.0% 1/5 • Number of events 1 • 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.	0.00% 0/6 • 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.

Other adverse events

Measure	Emapalumab n=5 participants at risk Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg Emapalumab: I.v. infusion every third day	Anakinra n=5 participants at risk Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours Anakinra: Daily i.v. infusion	Standard of Care n=6 participants at risk Standard of care according to local practice
Cardiac disorders Atrial Fibrillation	20.0% 1/5 • Number of events 2 • 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.	0.00% 0/5 • 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.	0.00% 0/6 • 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.
Musculoskeletal and connective tissue disorders Muscle Hematoma	20.0% 1/5 • Number of events 1 • 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.	0.00% 0/5 • 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.	0.00% 0/6 • 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.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/5 • 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.	20.0% 1/5 • Number of events 1 • 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.	0.00% 0/6 • 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.
Hepatobiliary disorders Hypertransaminasaemia	0.00% 0/5 • 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.	0.00% 0/5 • 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.	16.7% 1/6 • Number of events 1 • 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.

Additional Information

Henrick Andersson, Director of Statistical Science

Swedish Orphan Biovitrum

Phone: +46760011816

Email: henrik.andersson@sobi.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60