Rhu-pGSN for Severe Covid-19 Pneumonia
Condition: Sars-CoV2
MeSH terms: COVID-19; Pneumonia
Intervention: Recombinant human plasma gelsolin (Rhu-pGSN); Placebo
Intervention description: Intravenous administration of rhu-pGSN at 12 mg/kg, 3 doses; Normal saline in matched volume to treatment arm. Undistinguishable in syringe.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Intervention model description: Randomized, blinded, placebo controlled interventional
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Treatment blinded to all but unblinded pharmacist
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: COVID-19; Pneumonia; Severe; Cytokine storm

Summary:

      Study Objectives:

      Primary

        -  To assess the efficacy (survival without organ failure on Day 14) of three doses of
           rhu-pGSN administered intravenously (IV) plus standard of care (SOC) to hospitalized
           subjects with a primary diagnosis of COVID-19 pneumonia and a severity score of 4, 5 or
           6 on the World Health Organization (WHO) 9-point severity scale

        -  To evaluate the safety and tolerability of three IV doses of rhu-pGSN administered to
           hospitalized subjects with a primary diagnosis of COVID-19 pneumonia and a severity
           score of 4, 5, or 6 on the WHO 9-point severity scale

      Secondary

        -  To further assess the efficacy of IV administered rhu-pGSN

        -  To assess changes in WHO 9-point severity score for SOC with or without rhu-pGSN

        -  To evaluate the effect of administered rhu-pGSN on survival rates

        -  To assess the relationship of pGSN levels (and other biomarkers) at baseline with
           clinical outcomes

        -  [OPTIONAL] To follow the pharmacokinetics (PK) of administered rhu-pGSN

      Immunogenicity

      • To investigate the development of antibodies against rhu-pGSN post-treatment
    

Eligibility criteria:

        Inclusion Criteria:

          -  Hospitalized with laboratory-confirmed (RT-PCR+) or highly suspected (compatible with
             at least bilobar lung involvement without another plausible diagnosis) COVID-19

          -  Weight ≤100 kg

          -  Within 24 hours of reaching a WHO severity score of 4-6 either:

               -  At admission

               -  While already hospitalized

          -  Informed consent obtained from subject/next of kin/legal proxy

          -  Primary admitting diagnosis of pneumonia supported by a compatible clinical
             presentation with a documented infiltrate consistent with pneumonia on chest
             radiograph or CT as assessed by the admitting emergency-department (ED), clinic, or
             ward physician or equivalent caregiver

          -  Recommended (not mandatory) guidance/discretionary criteria defining patients with
             pneumonia satisfying all 4 categories below:

               -  At least 2 symptoms: difficulty breathing, cough, production of purulent sputum,
                  or chest pain

               -  At least 2 vital sign abnormalities: fever, tachycardia, or tachypnea (thresholds
                  -- fever: oral or core temperature >100.4 °F [38 °C]; heart rate >100 beats/min;
                  respiratory rate >24/min)

               -  At least one finding of other clinical signs and laboratory abnormalities:
                  hypoxemia (O2 saturation <90%), clinical evidence of pulmonary consolidation, or
                  leukocytosis or leukopenia

               -  Chest imaging or CT showing new (or presumed new or worsening) pulmonary
                  infiltrates

                    -  Principal investigator to note radiologic findings in the electronic case
                       report form (eCRF)

                    -  Radiology report to be placed in the eCRF

                    -  A copy of the radiograph attached to be saved for review

          -  A hyperinflammatory status (defined by increased ferritin ≥500 µg/L, D-dimer ≥1000
             ng/mL, or C-reactive protein (CRP) ≥75 mg/L)

          -  During the course of the study starting at screening and for at least 6 months after
             their final study treatment:

               -  Female subjects of childbearing potential must agree to use 2 medically accepted
                  birth control methods

               -  Male subjects with a partner who might become pregnant must agree to use reliable
                  forms of contraception (i.e., vasectomy, abstinence), or an acceptable method of
                  birth control must be used by the partner

               -  All subjects must agree not to donate sperm or eggs (ovocytes)

        Exclusion Criteria:

          -  A negative RT-PCR test for COVID-19 during the evaluation of the present illness

          -  Extracorporeal membrane oxygenation (ECMO)

          -  Pregnant or lactating women

          -  Active underlying cancer treated with systemic chemotherapy or radiation therapy
             during the last 30 days

          -  Transplantation of hematopoietic or solid organs

          -  Chronic mechanical ventilation or dialysis

          -  Otherwise unsuitable for study participation because of chronic, severe, end-stage,
             and life-limiting underlying disease unrelated to COVID-19 likely to interfere with
             management and assessment of acute pneumonia, only comfort or limited (non-aggressive)
             care is to be given, or life expectancy <6 months unrelated to acute COVID infection
             in the opinion of the Investigator