Safety and Efficacy of Dupilumab for Treatment of Hospitalized COVID-19 Patients

A total of 40 eligible subject were enrolled and randomized in a 1:1 ratio to receive either dupilumab or placebo, stratifying on the disease severity measured by the required oxygen ≤ 15L or > 15L by nasal cannula. Both arms received standard of care management per current National Institutes of Health (NIH) COVID-19 treatment guideline in addition to their randomized treatments. Patients were then followed prospectively for up to 360 days after enrollment.

As an extension to the randomized double-blind placebo-controlled trial assessing dupilumab for treatment of those hospitalized with acute moderate to severe COVID-19, subjects were followed up at 1 year for evaluation of pulmonary function testing (PFT), pulmonary imaging, immune biomarkers, neurocognition and symptoms.

Inclusion criteria

• Male or female 18 years of age or older at the time of enrollment.
• Patients hospitalized with a positive RT-PCR for SARS-CoV-2 within the last 14 days, with illness duration within the last 14 days, and evidence of moderate to severe COVID-19 infection as defined by NIH COVID-19 Severity Categorization (8):

• Moderate illness: Individuals who show evidence of lower respiratory disease during clinical assessment or imaging and who have saturation of oxygen SpO2≥ 94% on room air at sea level.
• Severe illness: Individuals who have SpO2 <94% on room air at sea level, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mm Hg, respiratory frequency >30 breaths/min, or lung infiltrates >50%.
• Patient and/or legally authorized representative is willing and able to provide written informed consent and comply with all protocol requirements.
• Patients with hematologic malignancies or solid tumors are eligible.
• Patients with autoimmune disorders are eligible.
• Patients with immunodeficiency and organ or stem cell transplant recipients are eligible.
• Patients with acute or chronic renal injury/failure are eligible.
• Patients with neutropenia/lymphopenia are eligible.
• Patients with elevated liver function tests are eligible.
• Women who are not taking contraception are eligible.
• Patients who are currently or have recently received steroids and/or remdesivir are eligible.
• Patient agrees to not participate in another clinical trial for the treatment of COVID-19 through end of study period.

Exclusion criteria

• Patients who do not require inpatient admission for COVID-19 infection.
• Patients who require invasive mechanical ventilation at time of enrollment.
• A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the individual at a substantially increased risk due to study participation.
• Pregnancy or breast feeding (lactating women who agree to discard breast milk from day 1 until two weeks after the last study product is given are not excluded).
• Allergy to Dupilumab or its excipients.
• Received any of the following in the two weeks prior to screening as treatment of COVID-19:
• small molecule tyrosine kinase inhibitors (e.g. imatinib, gefitinib, acalabrutinib, etc.);
• monoclonal antibodies targeting cytokines (e.g., TNF inhibitors, anti-interleukin-1 [IL-1], anti-IL-6 [or sarilumab], etc.);
• monoclonal antibodies targeting T-cells or B-cells as treatment for COVID-19;
• Any other immunomodulatory (other than steroids) medications within 5 half-lives or 30 days prior to randomization.
• Current acute parasitic helminth infection or history of chronic parasitic infection.
• History of ocular scleritis, uveitis, keratitis or recent (<6 months) eye injury (chemical or traumatic), infection or vascular occlusion.
• Have received any live vaccine (that is, live attenuated) within 4 weeks before screening, or intend to receive a live vaccine (or live attenuated) during the study. Note: Use of non-live (inactivated) vaccinations is allowed for all subjects.