Mavrilimumab in Severe COVID-19 Pneumonia and Hyper-inflammation (COMBAT-19) (COMBAT-19)

This is an interventional treatment trial for Covid-19 focused on measuring covid-19, Acute respiratory failure, mavrilimumab, GM-CSF, GM-CSF receptor alpha, SARS-CoV2, viral pneumonia Read More

Inclusion Criteria:

• Adults (≥ 18 years of age)
• Signed informed consent by any patient capable of giving consent, or, when the patient is not capable of giving consent, by his or her legal/authorized representative or according to local guidelines
• Patients clinically diagnosed with SARS-CoV-2 virus by PCR or by other approved diagnostic methodology
• Hospitalized with COVID-19-induced pneumonia evidenced by chest x-ray or CT scan with pulmonary infiltrates
• Patient requiring oxygen supplementation (i.e. with a SpO2 ≤ 92% while breathing room air) and having a PAO2/FIO2 ratio ≤ 300 mmHg

• Lactate dehydrogenase (LDH) > normal range and at least one of the following:

  1. fever > 38.0 °C;
  2. increased levels of C-reactive Protein (CRP) ≥ 10x UNL mg/L (≥ 60 mg/l);
  3. increased levels of ferritin ≥ 2.5x UNL ( ≥ 1000 μg/L)

Exclusion Criteria:

• Onset of COVID-19 pneumonia symptoms (i.e. dyspnea/respiratory insufficiency) >14 days
• On mechanical ventilation at the time of randomization
• A PaO2/FiO2 < 100 mmHg
• Uncontrolled systemic infection (other than COVID-19)
• Hypersensitivity to the active substance or to any of the excipients of the experimental drug
• Total neutrophil count < 1500/mm3
• Severe hepatic cirrhosis
• History of chronic HBV or HCV infection
• Known or active tuberculosis (TB) or a history of incompletely treated TB; suspected or known extrapulmonary tuberculosis
• Moderate/severe heart failure (NYHA Class 3 or 4)

• Any prior (within the defined periods below) or concurrent use of immunosuppressive therapies including but not limited to the following:

  1. Anti-IL-6, anti-IL-6R antagonists or Janus kinase inhibitors (JAKi) in the past 30 days or plans to receive during the study period;
  2. Cell-depleting agents (e.g., anti CD20) without evidence of recovery of B cells to baseline level;
  3. Anakinra within 1 week of baseline; canakinumab within 8 weeks of baseline; abatacept within 8 weeks of baseline.
  4. Tumor necrosis factor (TNF) inhibitors within 2-8 weeks (etanercept within 2 weeks, infliximab, certolizumab, golimumab, or adalimumab within 8 weeks), or after at least 5 half-lives have elapsed, whichever is longer;
  5. Alkylating agents including cyclophosphamide (CYC) within 6 months of baseline;
  6. Cyclosporine (CsA), azathioprine (AZA) or mycophenolate mofetil (MMF) or leflunomide or methotrexate within 4 weeks of baseline.
• Pregnancy or lactation (Note: Women of childbearing age should use effective contraception/abstinence after treatment with mavrilimumab and for 3 months after the dosing)
• Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
• In the opinion of the investigator, progression to death is imminent and highly likely within the next 24 hours, irrespective of the provision of treatments
• Current participation in any other interventional investigational trials