Safety and Efficacy of Dupilumab for Treatment of Hospitalized COVID-19 Patients
Condition: COVID-19
MeSH terms: COVID-19
Intervention: Dupilumab; Placebo
Intervention description: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.; Normal Saline.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Anti-Inflammatory Agents

Summary:

      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.
    

Eligibility criteria:

        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.