severe COVID-19 pneumonia MedDRA version: 23.0 Level: LLT Classification code 10084401 Term: COVID-19 respiratory infection System Organ Class: 100000004862
Conditions
Interventions
Product Name: rhu-pGSN
Product Code: recombinant human plasma Gelsolin
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: recombinant human plasma Gelsolin
Current Sponso
Sponsors
BioAegis Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion 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 - Age =18 years - 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 CXR 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 =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -To assess the efficacy (survival without organ failure on Day 14) of intravenous (IV) rhu-pGSN plus standard of care (SOC) vs placebo plus SOC (hereafter referred to as rhu-pGSN vs placebo) administered to hospitalized subjects with a primary diagnosis of Coronavirus 2019 (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 (incidence of serious adverse events [SAEs]) of IV 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 Objective: - To further assess the efficacy of IV administered rhu-pGSN - To measure changes in the WHO 9-point severity scale for SOC ± 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 ;Primary end point(s): Safety and tolerability - Incidence of SAEs in rhu-pGSN vs placebo group Efficacy -Proportion of subjects alive not on vasopressors, mechanical ventilator, and dialysis on Day 14 ;Timepoint(s) of evaluation of this end point: Safety and tolerability- 90 days Efficacy -Day 14 after start of study treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety and tolerability - Incidence, causality, and severity of AEs (graded according to the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) in rhu-pGSN vs placebo groups - Frequencies of new or worsening clinically significant laboratory abnormalities in rhu-pGSN vs placebo groups - Mortality rate irrespective of cause at Days 28 and 90 • Efficacy - 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, 14, 28, 60, and 90 without: ?Ongoing use of vasopressors ?Ongoing intubation/mechanical ventilation ?Ongoing residence in an ICU ?New ongoing need for dialysis/renal replacement therapy (RRT) - Proportion of subjects discharged to home or immediate prior residence by Day 28 - Days on the ventilator - Length of stay (LOS) in hospital and in ICU (days) - Re-admission to an acute-care hospital up to Day 90 • PK (Optional) - PK for rhu-pGSN including maximum concentration (Cmax), time to maximum concentration (Tmax), terminal half-life (T1/2), area under the curve from time zero to 8 hours (AUC0-8), area under the curve from time 0 to infinity (AUCinf) for Dose #1 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial). • Immunogenicity - Presence of anti pGSN antibodies on Days 1 (predose), 28, and 90 ;Timepoint(s) of evaluation of this end point: Days 7, 28, 60 (optional), and 90 | — |
Countries
Romania
Contacts
Public ContactSusan L. Levinson-Chief Executive O
BioAegis Therapeutics, Inc.
Outcome results
None listed