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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04324021
Recruitment Status : Recruiting
First Posted : March 27, 2020
Last Update Posted : September 7, 2020
Sponsor:
Information provided by (Responsible Party):
Swedish Orphan Biovitrum

Brief Summary:
As shown by the data available, hyper-inflammation, caused by a cytokine storm resulting from an exaggerated response of the immune system to the presence of the virus, is considered to represent one of the most important negative prognostic factor in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this study is to investigate new possibilities 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
SARS-CoV-2 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 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 : April 2, 2020
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Anakinra

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 Name: 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 Name: Kineret

No Intervention: Standard of care
Standard of care according to local practice



Primary Outcome Measures :
  1. Treatment success [ Time Frame: Up to Day 15 ]
    Defined as the proportion of patients not requiring invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO)


Secondary Outcome Measures :
  1. Time to mechanical ventilation [ Time Frame: Date of randomization to date of mechanical ventilation ]
    Measured in days

  2. Change from baseline in Modified Early Warning system score [ Time Frame: Baseline, Day 15 ]
    Measured in total score

  3. Change from baseline in resting peripheral capillary oxygen saturation (SpO2) [ Time Frame: Baseline, 3 assessments every Days 4, 7, 10, 13 and 15 ]
    Measured in percent (%)

  4. Change from baseline in partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) [ Time Frame: Baseline, Day 15 ]
    Measured in percent (%)

  5. Change of pH in hemogasanalysis from baseline [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  6. Change of carbon dioxide tension (pCO2) in hemogasanalysis from baseline [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  7. Change of oxygen tension (pO2) in hemogasanalysis from baseline [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  8. Change of potassium in hemogasanalysis from baseline [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  9. Change of sodium in hemogasanalysis from baseline [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  10. Change of chloride in hemogasanalysis from baseline [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  11. Change of lactic acid in hemogasanalysis from baseline [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  12. Change of hemoglobin in hemogasanalysis from baseline [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  13. Change from baseline in oxygen supplementation [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in l/min

  14. Change of findings of high-resolution computed tomography (CT) scan of the chest [ Time Frame: Screening, Day 15 ]
    Measured in scan evaluation: Normal, Abnormal but not clinically significant, Abnormal clinical significant, Not Done

  15. Change from baseline in Ferritin [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  16. Change from baseline in lactate dehydrogenase (LDH) [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  17. Change from baseline in D-dimers [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  18. Change from baseline in White Blood Cells with differential counts [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  19. Change from baseline in Red Blood Counts [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  20. Change from baseline in Hemoglobin [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  21. Change from baseline in Platelet count [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  22. Change from baseline in Fibrinogen [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  23. Change from baseline in Complement factors C3/C4 [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  24. Change from baseline in Prothrombin time [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  25. Change from baseline in Cardiac troponin [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  26. Change from baseline in aspartate aminotransferase (AST) [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  27. Change from baseline in alanine aminotransferase (ALT) [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  28. Change from baseline in total bilirubin levels [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  29. Change from baseline in C-Reactive Protein [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  30. Change from baseline in Creatinine [ Time Frame: Baseline, Days 4, 7, 10, 13 and 15 ]
    Measured in local units

  31. Overall survival [ Time Frame: Weeks 6 and 10 ]
    Confirmation of death

  32. Time to hospital discharge [ Time Frame: Weeks 6 and 10 ]
    Measured in days



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   30 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 > 30 to < 80 years at the time of screening.
  4. Presence of respiratory distress, defined as:

    1. PaO2/FiO2 < 300 mm Hg and >200 mm Hg or
    2. Respiratory Rate (RR) ≥30 breaths/min or
    3. SpO2 < 93 percent in air at rest. Note: Patients given continous positive airway pressure (CPAP) ventilator support are eligible for inclusion.
  5. Presence of hyperinflammation defined as:

    a. Lymphocyte counts < 1000 cells/µL, and b. Two of the following three criteria: i. Ferritin > 500ng/mL ii. LDH > 300 U/L iii. 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-s 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04324021


Contacts
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Contact: Cristina de Min, MD / CMO +46 8 697 20 00 sobi.immuno@sobi.com
Contact: Karin Becker, MSc sobi.immuno@sobi.com

Locations
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United States, Florida
University of Florida, College of Medicine Not yet recruiting
Gainesville, Florida, United States, 32611-5500
Contact: Sumita Bhaduri-McIntosh, MD         
United States, Minnesota
Regions hospital Recruiting
Saint Paul, Minnesota, United States, 55101
Contact: Elie Gertner, MD         
United States, New Jersey
The Valley hospital Not yet recruiting
Ridgewood, New Jersey, United States, 07450
Contact: Amit Tibb, MD         
United States, New York
NewYork-Presbyterian Queens Recruiting
Flushing, New York, United States, 11355
Contact: Nishant Prasad, MD         
United States, Pennsylvania
Temple University Hospital Not yet recruiting
Philadelphia, Pennsylvania, United States, 19140
Contact: Roberto Caricchio, MD         
United States, South Carolina
AnMed Health Pulmonary and Sleep Medicine Not yet recruiting
Anderson, South Carolina, United States, 29621
Contact: Abhijit Raval, MD         
United States, Utah
University of Utah Health Not yet recruiting
Salt Lake City, Utah, United States, 84108
Contact: Estelle Harris, MD         
Italy
ASST Spedali Civili di Brescia Dipartimento di Reumatologia e Immunologia Clinica Recruiting
Brescia, Italy
Contact: Franco Franceschini, Prof       franco.franceschini@unibs.it   
S.C. Malattie Infettive, Ospedale Galliera Not yet recruiting
Genova, Italy
Contact: Emanuele Pontali         
Ospedale Maggiore Policlinico, Dipartimento di Anestesia-Rianimazione e Medicina di Urgenza Recruiting
Milano, Italy
Contact: Antonio Pesenti, Prof       antonio.pesenti@policlinico.mi.it   
Dipartimento di Medicina - DIMED, Azienda Ospedale - Università Padova Not yet recruiting
Padova, Italy
Contact: Paolo Sfriso, Prof         
Azienda Ospedaliero-Universitaria di Parma, Dipartimento di Malattie infettive ed epatologia Recruiting
Parma, Italy
Contact: Gabriele Missale, Prof       gabriele.missale@unipr.it   
Contact: Prof         
Ospedale Lazzaro Spallanzani, Dipartimento di Malattie Infettive ad alta Intensità di cura ed altamente contagiose,Ospedale Lazzaro Spallanzani Recruiting
Roma, Italy
Contact: Emanuele Nicastri, Dr       Emanuele.nicastri@inmi.it   
ASL Città di Torino, Unit of Infectious Diseases, Medicine, Rheumatology Not yet recruiting
Torino, Italy
Contact: Giovanni Di Perri, Prof         
Sponsors and Collaborators
Swedish Orphan Biovitrum
Investigators
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Principal Investigator: Emanuele Nicastri, MD Direttore Dipartimento di Malattie Infettive
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Responsible Party: Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier: NCT04324021    
Other Study ID Numbers: Sobi.IMMUNO-101
2020-001167-93 ( EudraCT Number )
First Posted: March 27, 2020    Key Record Dates
Last Update Posted: September 7, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Infection
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents