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This study is a prospective, phase II, multi-center, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of mavrilimumab in hospitalized patients with acute respiratory failure requiring oxygen supplementation in COVID- 19 pneumonia and a hyper-inflammatory status. The study will randomize patients to mavrilimumab or placebo, in addition to standard of care per local practice. The total trial duration will be 12 weeks after single mavrilimumab or placebo dose.
Full description
To evaluate the efficacy and safety of mavrilimumab versus placebo in addition to best standard of care (SoC) in the treatment of COVID-19 pneumonia.
As of May 13, 2020, COVID-19 has been confirmed in more than 4.2 million people worldwide. Mortality rate has been reported to be approximately 3.7%, which is nearly 4 times higher than that of influenza: there is an urgent need for effective treatment.
Accumulating evidence suggests that patients with severe acute COVID-19 pneumonia have a cytokine storm syndrome, or unbalanced hyper-inflammatory response resulting in markedly elevated cytokine and chemokine production.
GM-CSF is a cytokine with dual roles as a critical pulmonary hormone and proinflammatory properties that can exaggerate tissue inflammation. Recent preliminary uncontrolled clinical observations on 13 non-mechanically-ventilated patients in the promoter institution suggest that GM-CSF pathway blockade with mavrilimumab is an effective and well-tolerated treatment for COVID-19 pneumonia.
We will perform a prospective, phase II, multi-center, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of mavrilimumab in hospitalized patients with acute respiratory failure requiring oxygen supplementation in COVID- 19 pneumonia and a hyper-inflammatory status. The study will randomize non-mechanically-ventilated adult patients to mavrilimumab or placebo, in addition to standard of care per local practice, which may include but not limited to anti-viral treatment, hydroxychloroquine, low-dose corticosteroids (≤ 10 mg of prednisone or equivalent) and/or supportive care. The total trial duration will be 12 weeks after single mavrilimumab or placebo infusion. Safety will be closely monitored by a dedicated external data safety monitoring board (DSMB) at regular intervals during the study.
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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:
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:
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
Primary purpose
Allocation
Interventional model
Masking
50 participants in 2 patient groups, including a placebo group
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Central trial contact
Giacomo De Luca, MD; Lorenzo Dagna, MD
Data sourced from clinicaltrials.gov
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