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
Efficacy and safety of IV rhu-pGSN on top of SOC will be evaluated initially in 60
participants representative of the drug target population: high-risk subjects with acute
severe pneumonia due to COVID-19. The rhu-pGSN dose will be based on actual body weight given
at 12 mg/kg. Three doses will be given at 0, 12 and 24 hours intervals promptly after
enrollment by IV infusion through a 0.2 µm filter. Participants will be randomized 1:1
rhu-pGSN or placebo. Interim safety analyses will be conducted after enrollment of 12, 24,
36, and 48 patients.
The primary efficacy outcome will be the proportion of patients surviving on Day 14 without
mechanical ventilation, vasopressors or dialysis. Secondary efficacy outcomes will include:
daily change in 9-point WHO severity score through at least Day 14; all-cause mortality at
Days 28 and 90; time to death (Kaplan-Meier survival analysis); proportion of subjects alive
on Days 7, 28, 60, and 90 without: ongoing use of vasopressors, ongoing intubation/mechanical
ventilation, ongoing residence in an intensive care unit (ICU), new ongoing need for
dialysis/renal replacement therapy; proportion of subjects discharged to home or immediate
prior residence by Day 28; days on the ventilator; length of stay in hospital and in ICU and
re-admission to an acute-care hospital up to Day 90. Safety of administration of rhu-pGSN at
the indicated dosage will also be evaluated.
Baseline and sequential levels of pGSN and inflammatory biomarkers will be measured. On days
1, 28, and 90, immunogenicity due to the formation of anti-pGSN antibodies will be assessed.
Drug: Recombinant human plasma gelsolin (Rhu-pGSN)
Intravenous administration of rhu-pGSN at 12 mg/kg, 3 doses
Other Name: gelsolin
Other: Placebo
Normal saline in matched volume to treatment arm. Undistinguishable in syringe.
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
Spitalul Clinic de Boli Infecţioase şi Pneumoftiziologie
Timişoara, Romania
Sant Joan de Reus SAM University Hospital
Reus, Spain
Hospital Universitari de Tarragona Joan XXIII
Tarragona, Spain
Mark J DiNubile, MD, Study Director
BioAegis Therapeutics Inc.