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

Sponsor
Swedish Orphan Biovitrum (Industry)
Overall Status
Terminated
CT.gov ID
NCT04324021
Collaborator
(none)
16
Enrollment
12
Locations
3
Arms
7.4
Actual Duration (Months)
1.3
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: Emapalumab
  • Biological: Anakinra
 Phase 2/Phase 3

Detailed Description

This is an open label, controlled, parallel group, 3-arm, multicenter study to assess the efficacy and safety of Emapalumab or Anakinra, versus standard of care (SoC). Patients between 30 and 80 years will be eligible to participate in the study. The study is planned to consist of three groups, each comprising 18 patients. Treatment will be randomized to either Emapalumab+SoC, Anakinra+SoC or only SoC for two weeks. Follow-up visit or phone calls will be made 4 and 8 weeks after end of treatment period.

Study Design

Study Type:
Interventional
Actual Enrollment :
16 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2/3, Randomized, Open-label, Parallel Group, 3-arm, Multicenter Study Investigating the Efficacy and Safety of Intravenous Administrations of Emapalumab, an Anti-interferon Gamma (Anti-IFNγ) Monoclonal Antibody, and Anakinra, an Interleukin-1(IL-1) Receptor Antagonist, Versus Standard of Care, in Reducing Hyper-inflammation and Respiratory Distress in Patients With SARS-CoV-2 Infection.
Actual Study Start Date :
Apr 2, 2020
Actual Primary Completion Date :
Nov 13, 2020
Actual Study Completion Date :
Nov 13, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: 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

Biological: Emapalumab
I.v. infusion every third day
Other Names:
  • Gamifant

    		•
    Active Comparator: Anakinra

    Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours

    Biological: Anakinra
    Daily i.v. infusion
    Other Names:
  • Kineret

    		•
    No Intervention: Standard of care

    Standard of care according to local practice

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Treatment Success [Up to Day 15]

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

    Secondary Outcome Measures

    1. Number of Participants Requiring Mechanical Ventilation [Date of randomization to date of mechanical ventilation, up to 15 Days]

      Measured in number of participants

    2. Change From Baseline in Modified Early Warning System Score [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

    3. Change From Baseline in Ferritin [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    4. Change From Baseline in Lactate Dehydrogenase (LDH) [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    5. Change From Baseline in D-dimers [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    6. Change From Baseline in Resting Peripheral Capillary Oxygen Saturation (SpO2) [Baseline, 3 assessments every Days 4, 7, 10, 13 and 15]

      Measured in percent (%)

    7. Change From Baseline in Oxygen Supplementation [Baseline, Days 4, 7, 10, 13 and 15.]

      Measured in l/min

    8. Change From Baseline in Partial Pressure of Oxygen/Fraction of Inspired Oxygen (PaO2/FiO2) [Baseline, Day 15]

      Measured in mmHg

    9. Number of Participants With Changes in High-resolution Computed Tomography (CT) Scan of the Chest [Screening, Day 15]

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

    10. Overall Survival [Weeks 6 and 10]

      Confirmation of death

    11. Number of Patients With Hospital Discharge [Until discharge up to Week 10]

      Measured in number of patients

    12. Change of Carbon Dioxide Tension (pCO2) in Hemogasanalysis From Baseline [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    13. Change of Oxygen Tension (pO2) in Hemogasanalysis From Baseline [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    14. Change of Potassium in Hemogasanalysis From Baseline [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    15. Change of Sodium in Hemogasanalysis From Baseline [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    16. Change of Chloride in Hemogasanalysis From Baseline [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    17. Change of Lactic Acid in Hemogasanalysis From Baseline [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    18. Change of Hemoglobin in Hemogasanalysis From Baseline [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    19. Change From Baseline in White Blood Cells With Differential Counts [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    20. Change From Baseline in Red Blood Counts [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    21. Change From Baseline in Hemoglobin [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    22. Change From Baseline in Platelet Count [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    23. Change From Baseline in Fibrinogen [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    24. Change From Baseline in Complement Factors C3/C4 [Day 15]

      Measured in local units

    25. Change From Baseline in Prothrombin Time [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    26. Change From Baseline in Cardiac Troponin [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    27. Change From Baseline in Aspartate Aminotransferase (AST) [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    28. Change From Baseline in Alanine Aminotransferase (ALT) [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    29. Change From Baseline in Total Bilirubin Levels [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    30. Change From Baseline in C-Reactive Protein [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    31. Change From Baseline in Creatinine [Baseline, Days 4, 7, 10, 13 and 15]

      Measured in local units

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Signed informed consent provided by the patient, or by the patient's legally authorized representative(s), as applicable.

    2. Documented presence of SARS-CoV-2 infection as per hospital routine.

    3. Age > 18 to < 85 years at the time of screening.

    4. Presence of respiratory distress, defined as:

    5. PaO2/FiO2 < 300 mm Hg and >200 mm Hg or

    6. Respiratory Rate (RR) ≥30 breaths/min or

    7. SpO2 < 93 percent in air at rest. Note: Patients given continous positive airway pressure (CPAP) ventilator support are eligible for inclusion.

    Presence of hyperinflammation defined as:
    1. Lymphocyte counts:

    • < 1000 cells/µL, in patients who have not received systemic glucocorticoids for at least 2 days prior to the assessment of the lymphocyte count

    • < 1200 cells/µL, in patients who have received systemic glucocorticoids for at least 2 days prior to the assessment of the lymphocyte count

    and

    1. One of the following three criteria:
    1. Ferritin > 500ng/mL

    1. LDH > 300 U/L

    2. D-Dimers > 1000 ng/mL

    Exclusion Criteria:

    1. Patients in mechanical ventilation or with modified early warning score (MEWS) >4 with evidence of moderate or above ARDS (Berlin definition, namely with PaO2/FiO2 >100, but <200 mm Hg) or severe respiratory insufficiency or evidence of rapid worsening (respiratory distress requiring mechanical ventilation or presence of shock or presence of concomitant organ failure requiring ICU admission). Note: For the evaluation of patient eligibility, temperature will not be considered in the calculation of the total MEWS score since presence of fever is a hallmark of SARS-CoV-2 infection

    2. Impairment of cardiac function defined as poorly controlled heart diseases, such as New York heart association (NYHA) class II (mild) and above, cardiac insufficiency, unstable angina pectoris, myocardial infarction within 1 year before enrollment, supraventricular or ventricular arrhythmia need treatment or intervention.

    3. Severe renal dysfunction (estimated glomerular filtration rate ≤ 30 mL/min/1.73 m2) or receive continuous renal replacement therapy, hemodialysis, or peritoneal dialysis.

    4. Uncontrolled hypertension (seated systolic blood pressure >180 mmHg, or diastolic blood pressure >110mmHg) .

    5. Administration of plasma from convalescent patients who recovered from SARS-CoV-2 infection.

    6. Clinical suspicion of latent tuberculosis.

    7. History of hypersensitivity or allergy to any component of the study drug.

    8. Pregnant women.

    9. Existence of any life-threatening co-morbidity or any other medical condition which, in the opinion of the investigator, makes the patient unsuitable for inclusion.

    10. Enrollment in another concurrent clinical interventional study, or intake of an investigational drug within three months or 5 half-lives prior to inclusion in this study, if considered interfering with this study objectives as assessed by the Investigator.

    11. Foreseeable inability to cooperate with given instructions or study procedures.

    12. Clinical suspicion of active mycobacteria, histoplasma capsulatum, herpes zoster, salmonella, and shigella Infections.

    13. Patients with liver dysfunction defined as AST or ALT > 5 × ULN

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Regions hospital Saint Paul Minnesota United States 55101
    2 The Valley hospital Ridgewood New Jersey United States 07450
    3 NewYork-Presbyterian Queens Flushing New York United States 11355
    4 Temple University Hospital Philadelphia Pennsylvania United States 19140
    5 University of Utah Health Salt Lake City Utah United States 84108
    6 ASST Spedali Civili di Brescia Dipartimento di Reumatologia e Immunologia Clinica Brescia Italy
    7 S.C. Malattie Infettive, Ospedale Galliera Genova Italy
    8 Ospedale Maggiore Policlinico, Dipartimento di Anestesia-Rianimazione e Medicina di Urgenza Milano Italy
    9 Dipartimento di Medicina - DIMED, Azienda Ospedale - Università Padova Padova Italy
    10 Azienda Ospedaliero-Universitaria di Parma, Dipartimento di Malattie infettive ed epatologia Parma Italy
    11 Ospedale Lazzaro Spallanzani, Dipartimento di Malattie Infettive ad alta Intensità di cura ed altamente contagiose,Ospedale Lazzaro Spallanzani Roma Italy
    12 ASL Città di Torino, Unit of Infectious Diseases, Medicine, Rheumatology Torino Italy

    Sponsors and Collaborators

    • Swedish Orphan Biovitrum

    Investigators

    • Principal Investigator: Emanuele Nicastri, MD, Direttore Dipartimento di Malattie Infettive

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Swedish Orphan Biovitrum
    ClinicalTrials.gov Identifier:
    NCT04324021
    Other Study ID Numbers:
    • Sobi.IMMUNO-101
    • 2020-001167-93
    First Posted:
    Mar 27, 2020
    Last Update Posted:
    Mar 10, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:
    Infections
    Interleukin 1 Receptor Antagonist Protein

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 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.
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Period Title: Overall Study
    STARTED 5 5 6
    COMPLETED 3 4 5
    NOT COMPLETED 2 1 1

    Baseline Characteristics

    Arm/Group Title Emapalumab Anakinra Standard of Care Total
    Arm/Group Description 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 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 according to local practice Total of all reporting groups
    Overall Participants 5 5 6 16
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    65.0
    (14.8)
    62.4
    (11.1)
    62.5
    (62.5)
    63.3
    (12.3)
    Sex: Female, Male (Count of Participants)
    Female
    1
    20%
    1
    20%
    0
    0%
    2
    12.5%
    Male
    4
    80%
    4
    80%
    6
    100%
    14
    87.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    20%
    1
    20%
    0
    0%
    2
    12.5%
    Not Hispanic or Latino
    4
    80%
    3
    60%
    5
    83.3%
    12
    75%
    Unknown or Not Reported
    0
    0%
    1
    20%
    1
    16.7%
    2
    12.5%
    Region of Enrollment (participants) [Number]
    Italy
    5
    100%
    5
    100%
    6
    100%
    16
    100%
    Hospitalization (Count of Participants)
    Count of Participants [Participants]
    5
    100%
    5
    100%
    6
    100%
    16
    100%
    Height (cm) (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    170.8
    (10.9)
    170.2
    (4.4)
    172.3
    (14.4)
    171
    (9.5)
    Weight (kg) (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    77.4
    (15.0)
    79.4
    (13.4)
    83.0
    (12.8)
    79.7
    (13)
    Symptom duration (days) (days) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [days]
    4.0
    (4.2)
    1.0
    (0)
    5.3
    (4.8)
    3.6
    (4.0)
    Oxygen levels (mmHg) (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    103.0
    (38.2)
    78.5
    (21.0)
    78.6
    (20.5)
    85.2
    (27.7)
    Fraction of Inspired oxygen (FiO2) (%) (% of inspired oxygen) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [% of inspired oxygen]
    61.8
    (29.9)
    54.8
    (37.1)
    53.2
    (22.4)
    56.3
    (27.4)

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Treatment Success
    Description Defined as the number of patients not requiring invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO)
    Time Frame Up to Day 15

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Count of Participants [Participants]
    3
    60%
    4
    80%
    5
    83.3%
    2. Secondary Outcome
    Title Number of Participants Requiring Mechanical Ventilation
    Description Measured in number of participants
    Time Frame Date of randomization to date of mechanical ventilation, up to 15 Days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Count of Participants [Participants]
    1
    20%
    1
    20%
    1
    16.7%
    3. Secondary Outcome
    Title Change From Baseline in Modified Early Warning System Score
    Description 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
    Time Frame Baseline, Day 15

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Mean (Standard Deviation) [scores on a scale]
    -1.00
    (0.00)
    0.00
    (0.82)
    -0.75
    (0.96)
    4. Secondary Outcome
    Title Change From Baseline in Ferritin
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from Baseline at D4
    -380.8
    (3026.3)
    -2864.2
    (3789.3)
    -770.2
    (1093.0)
    Change from Baselind at D7
    60.5
    (2503.4)
    -2179.6
    (3108.3)
    -1103.3
    (168.4)
    Change from Baselind at D10
    -527.5
    (3086.3)
    -2066.8
    (3342.9)
    -1295.0
    (359.8)
    Change from Baseline at D13
    -823.1
    (2792.5)
    -1931.1
    (3601.8)
    -1260.6
    (781.7)
    Change from baseline at D15
    -506.6
    (2518.2)
    -2045.2
    (3627.7)
    -842.6
    (1020.0)
    5. Secondary Outcome
    Title Change From Baseline in Lactate Dehydrogenase (LDH)
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from Baseline at D4
    -128.3
    (160.9)
    -31.8
    (13.0)
    -70.4
    (85.5)
    Change from Baseline at D7
    -164.3
    (267.4)
    -16.8
    (162.9)
    -96.0
    (107.3)
    Change from Baseline at D10
    -184.3
    (200.2)
    -60.4
    (76.4)
    -143.5
    (128.7)
    Change from Baseline at D13
    -185.3
    (260.9)
    -2.6
    (264.4)
    -155.0
    (121.0)
    Change from Baseline at D15
    -163.6
    (252.4)
    -20.6
    (274.8)
    -158.4
    (108.3)
    6. Secondary Outcome
    Title Change From Baseline in D-dimers
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from Baseline at D4
    -0.19
    (0.34)
    5.13
    (14.73)
    -2.05
    (1.65)
    Change from Baseline at D7
    -7.37
    (13.84)
    6.78
    (19.41)
    -4.30
    (1.96)
    Change from Baseline at D10
    -10.07
    (18.16)
    4.66
    (12.82)
    -7.18
    (5.96)
    Change from Baseline at D13
    -7.99
    (13.40)
    6.84
    (19.39)
    -5.67
    (7.11)
    Change from Baseline at D15
    -6.84
    (12.67)
    6.64
    (19.51)
    -5.55
    (6.45)
    7. Secondary Outcome
    Title Change From Baseline in Resting Peripheral Capillary Oxygen Saturation (SpO2)
    Description Measured in percent (%)
    Time Frame Baseline, 3 assessments every Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from baseline at D4
    -0.667
    (3.598)
    0.267
    (2.060)
    0.722
    (2.603)
    Change from baseline at D7
    0.867
    (2.923)
    0.667
    (1.748)
    2.000
    (2.415)
    Change from baseline at D10
    0.625
    (3.523)
    0.267
    (1.754)
    2.333
    (3.528)
    Change from baseline at D13
    1.358
    (2.140)
    -2.233
    (6.098)
    1.600
    (3.639)
    Change from baseline at D15
    -1.640
    (3.383)
    -2.400
    (5.771)
    2.944
    (2.840)
    8. Secondary Outcome
    Title Change From Baseline in Oxygen Supplementation
    Description Measured in l/min
    Time Frame Baseline, Days 4, 7, 10, 13 and 15.

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 4 6
    Change from baseline at D4
    0.0
    (0.0)
    2.8
    (5.5)
    -0.2
    (9.5)
    Change from baseline at D7
    -1.0
    (5.8)
    -1.8
    (4.8)
    -7.8
    (9.1)
    Change from baseline at D10
    -3.3
    (6.9)
    -2.3
    (6.2)
    -17.8
    (18.2)
    Change from baseline at D13
    -4.3
    (8.1)
    -3.3
    (7.8)
    -20.0
    (17.0)
    Change from baseline at D15
    -3.6
    (9.3)
    -4.3
    (7.9)
    -15.3
    (19.3)
    9. Secondary Outcome
    Title Change From Baseline in Partial Pressure of Oxygen/Fraction of Inspired Oxygen (PaO2/FiO2)
    Description Measured in mmHg
    Time Frame Baseline, Day 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Day 15 Data not available for the whole population
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 2 1 4
    Mean (Standard Deviation) [mmHg]
    28.98
    (106.66)
    51.19
    156.72
    (113.53)
    10. Secondary Outcome
    Title Number of Participants With Changes in High-resolution Computed Tomography (CT) Scan of the Chest
    Description Measured in scan evaluation: Normal, Abnormal but not clinically significant, Abnormal clinical significant, Not Done
    Time Frame Screening, Day 15

    Outcome Measure Data

    Analysis Population Description
    Data not available for all patients
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 Abnormal CS at screening 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 Abnormal CS at screening Standard of care according to local practice Abnormal CS at screening
    Measure Participants 4 4 4
    Normal
    0
    0%
    0
    0%
    1
    16.7%
    Abnormal (NC)
    1
    20%
    3
    60%
    1
    16.7%
    Abnormal (CS)
    3
    60%
    1
    20%
    2
    33.3%
    11. Secondary Outcome
    Title Overall Survival
    Description Confirmation of death
    Time Frame Weeks 6 and 10

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Count of Participants [Participants]
    2
    40%
    1
    20%
    0
    0%
    12. Secondary Outcome
    Title Number of Patients With Hospital Discharge
    Description Measured in number of patients
    Time Frame Until discharge up to Week 10

    Outcome Measure Data

    Analysis Population Description
    Hospital discharge
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Hospital Discharge
    3
    60%
    4
    80%
    5
    83.3%
    Terminated prior to discharge
    2
    40%
    1
    20%
    1
    16.7%
    13. Secondary Outcome
    Title Change of Carbon Dioxide Tension (pCO2) in Hemogasanalysis From Baseline
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from baseline at D4
    0.00
    (7.21)
    -1.00
    (3.46)
    2.00
    (5.77)
    Change from baseline at D7
    -0.33
    (9.45)
    1.00
    (1.41)
    5.46
    (5.68)
    Change from baseline at D10
    2.33
    (6.03)
    3.67
    (8.08)
    4.20
    (5.12)
    Change from baseline at D13
    0.30
    (9.48)
    6.50
    (3.54)
    0.25
    (4.11)
    Change from baseline at D15
    0.77
    (8.33)
    3.75
    (5.74)
    4.00
    (5.10)
    14. Secondary Outcome
    Title Change of Oxygen Tension (pO2) in Hemogasanalysis From Baseline
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from baseline at D4
    19.33
    (44.28)
    40.67
    (34.78)
    5.75
    (16.92)
    Change from baseline at D7
    19.33
    (36.56)
    18.50
    (13.44)
    23.64
    (35.04)
    Change from baseline at D10
    4.00
    (37.36)
    -1.33
    (11.93)
    4.00
    (43.73)
    Change from baseline at D13
    18.00
    (84.85)
    -12.00
    (5.66)
    24.25
    (36.04)
    Change from baseline at D15
    17.57
    (61.05)
    8.75
    (47.84)
    8.80
    (21.37)
    15. Secondary Outcome
    Title Change of Potassium in Hemogasanalysis From Baseline
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from baseline at D4
    0.55
    (0.92)
    -0.35
    (0.49)
    0.45
    (1.34)
    Change from baseline at D7
    0.45
    (1.20)
    0.40
    0.53
    (0.93)
    Change from baseline at D10
    0.25
    (0.92)
    0.25
    (0.49)
    0.43
    (1.22)
    Change from baseline at D13
    -0.50
    0.10
    0.10
    (0.85)
    Change from baseline at D15
    0.00
    (0.71)
    0.03
    (0.75)
    0.17
    (0.47)
    16. Secondary Outcome
    Title Change of Sodium in Hemogasanalysis From Baseline
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from baseline at D4
    3.0
    (5.7)
    -0.5
    (2.1)
    -4.5
    (2.1)
    Change from baseline at D7
    1.0
    (1.4)
    -5.0
    0.3
    (4.0)
    Change from baseline at D10
    2.0
    (4.2)
    -3.0
    (7.1)
    1.3
    (1.2)
    Change from baseline at D13
    -2.0
    -6.0
    -1.0
    (1.4)
    Change from Baseline at D15
    2.5
    (6.4)
    0.0
    (2.6)
    0.7
    (2.1)
    17. Secondary Outcome
    Title Change of Chloride in Hemogasanalysis From Baseline
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from baseline at D4
    2.0
    (5.7)
    -0.5
    (2.1)
    1.5
    (2.1)
    Change from baseline at D7
    0.5
    (0.7)
    -4.0
    2.5
    (0.7)
    Change from baseline at D10
    0.0
    (2.8)
    -4.5
    (3.5)
    4.0
    (1.4)
    Change from baseline at D13
    -1.0
    -4.0
    3.0
    Change from baseline at D15
    2.0
    (4.2)
    -2.0
    (3.0)
    3.0
    (2.8)
    18. Secondary Outcome
    Title Change of Lactic Acid in Hemogasanalysis From Baseline
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from baseline at D4
    0.20
    0.00
    (0.28)
    -0.45
    (1.20)
    Change from baseline at D7
    0.70
    1.80
    0.00
    (0.85)
    Change from baseline at D10
    0.90
    1.20
    (0.17)
    -0.50
    (0.28)
    Change from baseline at D13
    0.10
    0.20
    Change from baseline at D15
    0.00
    1.27
    (1.16)
    -0.05
    (0.07)
    19. Secondary Outcome
    Title Change of Hemoglobin in Hemogasanalysis From Baseline
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from baseline at D4
    -34.0
    (46.7)
    -15.5
    (10.6)
    8.0
    (2.8)
    Change from baseline at D7
    -41.0
    (65.1)
    3.0
    6.7
    (1.5)
    Change from baseline at D10
    -34.0
    (62.2)
    7.5
    (6.4)
    -1.7
    (9.5)
    Change from baseline at D13
    -73.0
    2.0
    -6.5
    (20.5)
    Change from baseline at D15
    -38.0
    (49.5)
    -3.0
    (18.0)
    -4.0
    (15.9)
    20. Secondary Outcome
    Title Change From Baseline in White Blood Cells With Differential Counts
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from baseline at D4
    1.000
    (4.408)
    0.294
    (0.886)
    0.332
    (3.009)
    Change from baseline at D7
    0.340
    (2.623)
    2.812
    (2.953)
    1.738
    (4.165)
    Change from baseline at D10
    2.728
    (1.867)
    4.796
    (3.091)
    0.806
    (3.643)
    Change from baseline at D13
    1.548
    (5.265)
    1.588
    (2.653)
    -0.318
    (4.079)
    Change from baseline at D15
    1.686
    (4.395)
    1.070
    (2.420)
    1.878
    (4.788)
    21. Secondary Outcome
    Title Change From Baseline in Red Blood Counts
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from baseline at D4
    -0.260
    (0.470)
    -0.022
    (0.351)
    -0.108
    (0.359)
    Change from baseline at D7
    -0.385
    (0.732)
    0.016
    (0.422)
    -0.196
    (0.465)
    Change from baseline at D10
    -0.415
    (0.875)
    0.220
    (0.435)
    -0.262
    (0.549)
    Change from baseline at D13
    -0.350
    (1.254)
    0.106
    (0.395)
    -0.275
    (0.564)
    Change from baseline at D15
    -0.510
    (0.969)
    0.004
    (0.531)
    -0.163
    (0.571)
    22. Secondary Outcome
    Title Change From Baseline in Hemoglobin
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from baseline at D4
    -6.2
    (14.6)
    0.8
    (7.0)
    -3.5
    (9.1)
    Change from baseline at D7
    -9.3
    (21.3)
    0.8
    (13.1)
    -6.2
    (10.7)
    Change from baseline at D10
    -11.3
    (24.5)
    6.6
    (11.9)
    -8.0
    (16.0)
    Change from baseline at D13
    -10.8
    (36.8)
    2.8
    (13.6)
    -8.2
    (17.3)
    Change from baseline at D15
    -14.0
    (28.8)
    0.00
    (15.6)
    -3.7
    (16.9)
    23. Secondary Outcome
    Title Change From Baseline in Platelet Count
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Day 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from baseline at D4
    29.0
    (77.2)
    85.4
    (76.7)
    9.8
    (153.7)
    Change from baseline at D7
    19.8
    (116.6)
    140.4
    (191.8)
    47.4
    (232.9)
    Change from baseline at D10
    -3.8
    (142.5)
    129.8
    (223.9)
    9.0
    (232.8)
    Change from baseline at D13
    -32.0
    (126.5)
    80.8
    (213.2)
    -53.8
    (191.9)
    Change from baseline at D15
    -37.6
    (129.0)
    41.2
    (169.3)
    -67.2
    (158.1)
    24. Secondary Outcome
    Title Change From Baseline in Fibrinogen
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Days 4, 7, 10, 13 and 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from baseline at D4
    -1.435
    (3.137)
    -2.434
    (1.830)
    -0.088
    (4.582)
    Change from baseline at D7
    -3.925
    (6.113)
    -4.898
    (2.610)
    -1.147
    (7.883)
    Change from baseline at D10
    -3.535
    (8.998)
    -4.980
    (2.625)
    -5.562
    (5.089)
    Change from baseline at D13
    -2.587
    (9.308)
    -6.227
    (2.627)
    -5.479
    (5.027)
    Change from baseline at D15
    -0.588
    (9.210)
    -6.380
    (2.357)
    -4.596
    (5.624)
    25. Secondary Outcome
    Title Change From Baseline in Complement Factors C3/C4
    Description Measured in local units
    Time Frame Day 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Day 15
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    C3
    0.054
    (0.094)
    -0.068
    (0.222)
    -0.020
    (0.581)
    C4
    0.024
    (0.043)
    -0.108
    (0.080)
    -0.007
    (0.192)
    26. Secondary Outcome
    Title Change From Baseline in Prothrombin Time
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Day 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 4 2 2
    Change from baseline at D4
    -0.867
    (0.058)
    0750
    (0.071)
    -0.550
    (1.344)
    Change from baseline at D7
    -1.250
    (0.071)
    0.300
    (0.283)
    -2.100
    Change from Baseline at D10
    -1.003
    (0.895)
    -0.150
    (0.919)
    -1.700
    Change from Baseline at D13
    -2.250
    (0.354)
    0.050
    (0.495)
    -1.600
    Change from baseline at D15
    -1.278
    (1.087)
    -0.150
    (0.778)
    -0.800
    (1.697)
    27. Secondary Outcome
    Title Change From Baseline in Cardiac Troponin
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Day 15 Data not available for the whole population
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 1 0 2
    Change from Baseline at D4
    -0.017
    0.002
    (0.002)
    Change from Baseline at D7
    -0.022
    0.001
    (0.001)
    Change from Baseline at D10
    -0.022
    -0.001
    (0.001)
    Change from Baseline at D13
    -0.021
    -0.001
    (0.001)
    Change from Baseline at D15
    -0.022
    -0.001
    (0.001)
    28. Secondary Outcome
    Title Change From Baseline in Aspartate Aminotransferase (AST)
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Day 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from baseline at D4
    -46.0
    (79.8)
    -19.2
    (32.0)
    -63.2
    (146.0)
    Change from Baseline at D7
    -52.8
    (107.0)
    -27.6
    (36.8)
    -65.4
    (171.1)
    Change from Baseline at D10
    -53.3
    (108.6)
    -27.8
    (32.9)
    -79.8
    (170.6)
    Change from Baseline at D13
    -44.0
    (119.3)
    -25.2
    (28.9)
    -83.6
    (163.2)
    Change from baseline at D15
    -35.4
    (105.3)
    -25.8
    (28.3)
    -77.7
    (151.0)
    29. Secondary Outcome
    Title Change From Baseline in Alanine Aminotransferase (ALT)
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Day 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from Baseline D4
    -74.8
    (152.9)
    2.6
    (38.8)
    -23.6
    (148.8)
    Change from Baseline D7
    -97.5
    (237.1)
    16.6
    (66.9)
    -62.0
    (251.3)
    Change from Baseline D10
    -107.8
    (258.3)
    5.0
    (54.5)
    -107.0
    (350.0)
    Change from Baseline D13
    -111.0
    (293.3)
    -4.8
    (51.9)
    -119.2
    (352.2)
    Change from Baseline at D15
    -90.6
    (260.7)
    -5.8
    (53.2)
    -121.8
    (309.1)
    30. Secondary Outcome
    Title Change From Baseline in Total Bilirubin Levels
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Day 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from Baseline at D4
    -0.171
    (3.519)
    -1.129
    (12.314)
    0.376
    (2.600)
    Change from Baseline D7
    -1.496
    (4.011)
    -0.376
    (15.492)
    0.684
    (9.922)
    Change from Baseline D10
    -0.385
    (4.598)
    4.685
    (21.108)
    0.787
    (11.931)
    Change from Baseline D13
    -1.710
    (4.413)
    13.885
    (30.276)
    3.591
    (14.146)
    Change from Baseline at D15
    -3.523
    (4.473)
    14.125
    (29.771)
    -0.057
    (9.046)
    31. Secondary Outcome
    Title Change From Baseline in C-Reactive Protein
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Day 15. Data not available for the whole population
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from Baseline D4
    -53.73
    (98.88)
    -20.66
    (22.29)
    -12.65
    (12.81)
    Change from Baseline D7
    -63.65
    (101.74)
    -19.20
    (30.95)
    -10.98
    (19.57)
    Change from Baseline D10
    -60.05
    (106.21)
    -20.70
    (30.57)
    -14.60
    (15.72)
    Change from Baseline D13
    -60.50
    (106.66)
    -8.26
    (50.51)
    -16.33
    (14.27)
    Change from Baseline D15
    -38.96
    (103.48)
    -8.32
    (50.53)
    -15.26
    (12.71)
    32. Secondary Outcome
    Title Change From Baseline in Creatinine
    Description Measured in local units
    Time Frame Baseline, Days 4, 7, 10, 13 and 15

    Outcome Measure Data

    Analysis Population Description
    Change from baseline at Day 15 Data not available for all patients at all timepoints
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    Measure Participants 5 5 6
    Change from Baseline D4
    -6.542
    (9.430)
    1.414
    (8.516)
    -6.041
    (8.148)
    Change from Baseline D7
    -8.840
    (14.454)
    0.530
    (6.893)
    0.000
    (6.156)
    Change from Baseline D10
    -7.514
    (14.481)
    0.000
    (5.830)
    -0.530
    (5.506)
    Change from Baseline D13
    -5.304
    (20.171)
    0.000
    (8.928)
    -1.945
    (3.088)
    Change from Baseline D15
    -9.901
    (19.281)
    -0.354
    (9.756)
    -5.746
    (24.292)

    Adverse Events

    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.
    Adverse Event Reporting Description
    Arm/Group Title Emapalumab Anakinra Standard of Care
    Arm/Group Description 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 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 according to local practice
    All Cause Mortality
    Emapalumab Anakinra Standard of Care
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/5 (40%) 1/5 (20%) 0/6 (0%)
    Serious Adverse Events
    Emapalumab Anakinra Standard of Care
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/5 (40%) 1/5 (20%) 0/6 (0%)
    Respiratory, thoracic and mediastinal disorders
    End-stage respiratory failure 2/5 (40%) 2 0/5 (0%) 0 0/6 (0%) 0
    Respiratory failure 1/5 (20%) 1 1/5 (20%) 1 0/6 (0%) 0
    Other (Not Including Serious) Adverse Events
    Emapalumab Anakinra Standard of Care
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/5 (20%) 1/5 (20%) 1/6 (16.7%)
    Blood and lymphatic system disorders
    Thrombocytopenia 0/5 (0%) 0 1/5 (20%) 1 0/6 (0%) 0
    Cardiac disorders
    Atrial Fibrillation 1/5 (20%) 2 0/5 (0%) 0 0/6 (0%) 0
    Hepatobiliary disorders
    Hypertransaminasaemia 0/5 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1
    Musculoskeletal and connective tissue disorders
    Muscle Hematoma 1/5 (20%) 1 0/5 (0%) 0 0/6 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Henrick Andersson, Director of Statistical Science
    Organization Swedish Orphan Biovitrum
    Phone +46760011816
    Email henrik.andersson@sobi.com
    Responsible Party:
    Swedish Orphan Biovitrum
    ClinicalTrials.gov Identifier:
    NCT04324021
    Other Study ID Numbers:
    • Sobi.IMMUNO-101
    • 2020-001167-93
    First Posted:
    Mar 27, 2020
    Last Update Posted:
    Mar 10, 2022
    Last Verified:
    Mar 1, 2022