Study of Efficacy and Safety of DV890 in Patients With COVID-19 Pneumonia
Condition: COVID-19 Pneumonia, Impaired Respiratory Function
MeSH terms: COVID-19; Pneumonia; Respiratory Insufficiency
Intervention: DFV890; Standard of Care (SoC)
Intervention description: DFV890 25 mg tablets orally/nasogastrically administered 50 mg b.i.d for 14 days in addition to SoC.; SoC included a variety of supportive therapies that ranged from the administration of supplementary oxygen to full intensive care support, alongside the use of antiviral treatment, convalescent plasma, corticosteroids, antibiotics or other agents.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 143.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: COVID-19 pneumonia; SARS-CoV-2; APACHE II; DFV890; inflammasome

Summary:

      This clinical study was designed to assess the efficacy and safety of DFV890 for the
      treatment of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infected patients
      with coronavirus disease 2019 (COVID-19) pneumonia and impaired respiratory function.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female patients aged 18-80 years inclusive at screening.

          -  Clinically diagnosed with the SARS-CoV-2 virus by polymerase chain reaction (PCR) or
             by other approved diagnostic methodology within 7 days prior to randomization.

          -  Hospitalized with COVID-19-induced pneumonia evidenced by chest X-ray, computed
             tomography scan (CT scan) or magnetic resonance scan (MR scan), taken within 5 days
             prior to randomization (within 24 hours in patients in the Netherlands).

          -  Impaired respiratory function, defined as peripheral oxygen saturation (SpO2) ≤93% on
             room air or partial pressure of oxygen (PaO2) / fraction of inspired oxygen (FiO2)
             <300 millimeter of mercury (mmHg) at screening. For cities located at altitudes
             greater than 2500 m above sea level, these will be substituted with SpO2 <90% and
             PaO2/FiO2 <250 mmHg.

          -  APACHE II score of ≥10 at screening.

          -  C-reactive protein (CRP) ≥20 mg/L and/or ferritin level ≥600 μg/L at screening.

          -  Body mass index of ≥18 to <40kg/m2 at screening.

        Exclusion Criteria:

          -  Suspected active or chronic bacterial (including Mycobacterium tuberculosis), fungal,
             viral, or other infection (besides SARS-CoV-2).

          -  In the opinion of the investigator, progression to death is imminent and inevitable
             within the next 24 hours, irrespective of the provision of treatment.

          -  Intubated prior to randomization.

          -  Previous treatment with anti-rejection and immunomodulatory drugs within the past 2
             weeks, or within the past 30 days or 5 half-lives (whichever is the longer) for
             immunomodulatory therapeutic antibodies or prohibited drugs, with the exception of
             hydroxychloroquine, chloroquine or corticosteroids:

        For COVID-19 infection, ongoing corticosteroid treatment is permitted at doses as per local
        SoC.For non-COVID-19 disorders, ongoing corticosteroid treatment is permitted at doses up
        to and including prednisolone 10 mg daily or equivalent.

        In patients in the Netherlands only, the use of hydroxychloroquine and/or chloroquine in
        the past 2 weeks are exclusionary.

          -  Serum alanine transaminase (ALT) or aspartate transaminase (AST) >5 times upper limit
             of normal detected within 24 hours at screening or at baseline (according to local
             laboratory reference ranges) or other evidence if severe hepatic impairment
             (Child-Pugh Class C).

          -  Absolute peripheral blood neutrophil count of ≤1000/mm3.

          -  Estimated GFR (eGFR) ≤30 mL/min/1.73m2 (based on CKD-EPI formula).

          -  Patients currently being treated with drugs known to be strong or moderate inducers of
             isoenzyme CYP2C9 and/or strong inhibitors of CYP2C9 and/or strong inducers of
             cytochrome P450, family 3, subfamily A (CYP3A) and the treatment cannot be
             discontinued or switched to a different medication prior to starting study treatment.

          -  Patients with innate or acquired immunodeficiencies.

          -  Patients who have undergone solid organ or stem cell transplantation.