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

Safety and Efficacy of the Treatment of Hospitalized Patients With COVID 19 Infection With an Inhibitor of IL-4 and IL-13 Signaling: A Phase IIa Trial

This is a randomized, double-blind, placebo-controlled, superiority phase IIa trial to assess the safety and efficacy of dupilumab use in hospitalized patients with moderate to severe COVID-19 infection. Subsequently, we conducted a 1 year follow up study to investigate the occurrence of Post COVID conditions (PCC) in our study population through assessment of pulmonary function, symptoms, neurocognition and immune biomarkers to observe for any treatment group differences.

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.