Personalised Immunotherapy for SARS-CoV-2 (COVID-19) Associated With Organ Dysfunction

NCT04339712 | Completed Phase 2

• 2 other identifiers: ESCAPE2020-001039-29
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 17

Brief Summary

Our aim is to conduct one trial of personalized immunotherapy in patients with SARS-CoV-2 (COVID-19) associated with organ dysfunction and with laboratory findings of macrophage activation syndrome or immune dysregulation. These patients will be selected by the use of a panel of biomarkers and laboratory findings and they will be allocated to immunotherapy treatment according to their needs.

Conditions

COVID-19; Virus Diseases; Macrophage Activation Syndrome; Corona Virus Infection

Keywords

COVID-19; SARS-CoV-2; MAS; Anakinra; Tocilizumab

Outcome Measures

Primary Outcomes (3)

• Change of baseline total sequential organ failure assessment (SOFA) score

  At least 25% decrease between baseline sequential organ failure assessment SOFA score and measured sequential organ failure assessment SOFA score at Study Day 8

  Visit study day 8

• Improvement of lung involvement measurements

  Resolution of all criteria of lower respiratory tract involvemed that led to study inclusion (except findings from imaging studies) at Study Day 8

  Visit study day 8

• Increase of pO2/FiO2 ratio

  At least 50% increase of pO2/FiO2 ratio between baseline and study visit Day 8

  Visit Study Day 8

Secondary Outcomes (10)

• Comparison of change of baseline total sequential organ failure assessment (SOFA) score in enrolled subjects towards historical comparators

  Screening, Day 8

• Comparison of change of lung involvement measurements in enrolled subjects towards historical comparators

  Screening, Day 8

• Comparison of pO2/FiO2 ratio in enrolled subjects towards historical comparators

  Screening, Day 8

• Change of sequential organ failure assessment (SOFA) score

  Day 28

• Rate of Mortality

  Day 28

Study Arms (2)

anakinra

EXPERIMENTAL

In case of diagnosis of MAS, IV anakinra 200mg three times daily (every eight hours) for 7 days. Patients who will receive anakinra treatment and who suffer from kidney dysfunction will receive 50% of the dose i.e. 100mg anakinra three times daily for 15 days

Drug: Anakinra

tocilizumab

EXPERIMENTAL

In case of diagnosis of immune dysregulation IV tocilizumab 8mg/kg body weight once up to a maximum of 800mg. These patients will receive anakinra at the above dose in case they meet one of the following contra-indications for tocilizumab: 1. absolute neutrophil count less than 2,500/mm3; 2. absolute platelet count less than 100,000/mm3; and 3. AST or ALT more than 1.5 x the upper normal limit

Drug: Tocilizumab

Interventions

Anakinra DRUG

In case of diagnosis of MAS treatment with anakinra

Also known as: kineret

anakinra

Tocilizumab DRUG

In case of diagnosis of immune dysregulation treatment with tocilizumab

Also known as: RoActemra

tocilizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age equal to or above 18 years
• Male or female gender
• In case of women, unwillingness to remain pregnant during the study period.
• Written informed consent provided by the patient or by one first-degree relative/spouse in case of patients unable to consent
• Confirmed infection by SARS-CoV-2 virus using molecular techniques as defined by the World Health Organization11
• Organ dysfunction defined as the presence of at least one of the following conditions:
• Total SOFA score greater than or equal to 2;
• Involvement of the lower respiratory tract
• Laboratory documentation of MAS or immune dysregulation. MAS is documented by the findings of any serum ferritin greater than 4,420ng/ml. immune dysregulation is documented by the combination of two findings: a) serum ferritin equal to or lower than 4,420ng/ml; and b) less than 5,000 receptors of the membrane molecule of HLA-DR on the cell membrane of blood CD14-monocytes or less than 30 MFI of HLA-DR on the cell membrane of blood CD14-monocytes as counted by flow cytometry

You may not qualify if:

• Age below 18 years
• Denial for written informed consent
• Any stage IV malignancy
• Any do not resuscitate decision
• Active tuberculosis (TB) as defined by the co-administration of drugs for the treatment of TB
• Infection by the human immunodeficiency virus (HIV)
• Any primary immunodeficiency
• Oral or IV intake of corticosteroids at a daily dose equal or greater than 0.4 mg prednisone or greater the last 15 days.
• Any anti-cytokine biological treatment the last one month
• Medical history of systemic lupus erythematosus
• Medical history of multiple sclerosis or any other demyelinating disorder.

Sponsors & Collaborators

• Hellenic Institute for the Study of Sepsis: lead

Study Sites (17)

2nd Department of Critical Care Medicine, ATTIKON University Hospital

Athens, Haidari, 12462, Greece

Location

Intensive Care Unit, Ioannina University Hospital

Ioannina, Ioannina, 45500, Greece

Location

Department of Internal Medicine, Patras University Hospital

Pátrai, Rion, 26504, Greece

Location

Department of Internal Medicine, I PAMMAKARISTOS Hospital

Athens, 11144, Greece

Location

Intensive Care Unit, General Hospital of Athens KORGIALENIO-BENAKIO E.E.S.

Athens, 11526, Greece

Location

1st Department of Pulmonary Medicine and Intensive Care Unit

Athens, 11527, Greece

Location

Intensive Care Unit, General Hospital of Athens IPPOKRATEIO

Athens, 11527, Greece

Location

4th Department of Internal Medicine, Attikon University Hospital

Athens, 12462, Greece

Location

Intensive Care Unit, General Hospital ASKLEPIEIO Voulas

Athens, 16673, Greece

Location

Intensive Care Unit, "Latsio", Thriasio Elefsis General Hospital

Elefsina, 19600, Greece

Location

Intensive Care Unit, "Koutlimbaneio & Triantafylleio" Larissa General Hospital

Larissa, 41221, Greece

Location

Department of Internal Medicine, Larissa University Hospital

Larissa, 41334, Greece

Location

Intensive Care Unit, AGIOS DIMITRIOS General Hospital of Thessaloniki

Thessaloniki, 54 634, Greece

Location

Intensive Care Unit, G. GENNIMATAS General Hospital of Thessaloniki

Thessaloniki, 546 35, Greece

Location

Intensive Care Unit, Theageneio Oncological Hospital of Thessaloniki

Thessaloniki, 546 39, Greece

Location

Intensive Care Unit, General Hospital of Thessaloniki IPPOKRATEIO

Thessaloniki, 546 42, Greece

Location

Department of Anesthesiology and Intensive Care Medicine, University General Hospital of Thessaloniki AHEPA

Thessaloniki, 54636, Greece

Location

MeSH Terms

Conditions

COVID-19; Virus Diseases; Macrophage Activation Syndrome; Coronavirus Infections

Interventions

Interleukin 1 Receptor Antagonist Protein; tocilizumab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Apostolos Armaganidis, MD, PhD

  National Kapodistrian University of Athens, Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Treatment with tocilizumab or anakinra

Study Record Dates

• First Submitted: April 1, 2020
• First Posted: April 9, 2020
• Study Start: April 2, 2020
• Primary Completion: December 1, 2020
• Study Completion: January 8, 2021
• Last Updated: January 11, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

GR (17)