Study of Efficacy and Safety of MAS825 in Patients With COVID-19
Condition: COVID-19 Pneumonia, Impaired Respiratory Function
MeSH terms: COVID-19; Pneumonia; Respiratory Insufficiency
Intervention: MAS825; Placebo; Standard of Care (SoC)
Intervention description: MAS825 liquid solution for intravenous infusion; Placebo liquid solution for intravenous infusion; 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: Double (Participant, Investigator)
Enrollment: 140.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: COVID-19; pneumonia; SARS-Cov2; APACHE II; MAS825; inflammasome

Summary:

      This clinical study was designed to assess the efficacy and safety of MAS825 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:

          1. Male and female patients aged ≥18 years at screening

          2. Signed Informed Consent Form (ICF) by patient capable of giving consent, or, when the
             patient is not capable of giving consent, by his or her legal/authorized
             representative (if allowed according to local requirements)

          3. 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

          4. 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)

          5. 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 time of 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

          6. Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II score of ≥10 at
             time of screening

          7. CRP ≥20 mg/L or ferritin level ≥600 μg/L at screening

          8. Body weight between 45 kg and 145 kg, inclusive, at screening

          9. Ability to comply with the study protocol, in the investigator's judgment

        Exclusion Criteria:

          1. History of hypersensitivity to the investigational treatment or their excipients or to
             drugs of similar chemical classes

          2. Suspected active or chronic bacterial (including Mycobacterium tuberculosis), fungal,
             viral, or other infection with the exception of SARS-CoV-2

          3. In the opinion of the investigator, progression to death is imminent and inevitable
             within the next 24 hours, irrespective of the provision of treatment

          4. Intubated prior to randomization

          5. Patients who have explicitly expressed the wish not to receive intensive care support
             when this would be indicated based on their condition

          6. 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
             anti-viral therapies 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.

          7. Serum alanine transaminase (ALT) or aspartate transaminase (AST) >5 times upper limit
             of normal detected within 24 hours at screening/baseline (according to local
             laboratory reference ranges) or other evidence of severe hepatic impairment.

          8. Absolute peripheral blood neutrophil count of ≤1000/mm^3

          9. Estimated GFR (eGFR) ≤30 mL/min/1.73m^2 (based on CKD-EPI formula)

         10. Pregnant or breastfeeding, or positive urine or serum pregnancy test in a pre-dose
             examination

         11. 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

         12. Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, unless they agree to abstain from any sexual intercourse for a
             total of 29 days after randomization (the 14-day treatment period plus a 14-day
             follow-up period).

         13. Current participation in any other investigational trials, with the exception of (not
             yet) approved COVID-19 therapies that are considered (local) standard of care.