Rhu-pGSN for Severe Covid-19 Pneumonia

Phase 2

Completed

Conditions: Sars-CoV2

Interventions: Other: Placebo
Drug: Recombinant human plasma gelsolin (Rhu-pGSN)

Registration Number: NCT04358406

Lead Sponsor: BioAegis Therapeutics Inc.

Brief 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

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 64

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Normal saline in matched volume to treatment arm. Undistinguishable in syringe.
Rhu-pGSN	Recombinant human plasma gelsolin (Rhu-pGSN)	Recombinant human plasma gelsolin reconstituted for slow bolus injection.

Primary Outcome Measures

Name	Time	Method
Efficacy: Proportion of Subjects Alive Not on Vasopressors, Mechanical Ventilator, or Dialysis	Day 14	Number and percentage of subjects alive on Day 14 without ongoing use of vasopressors, ongoing intubation/mechanical ventilation, or new/ongoing need for dialysis/RRT. Subjects who discontinued from the study early or whose survival status was inconclusive on Day 14 were considered as a failure (Not Alive).
Safety: Number of Subjects With SAEs	Day 1 through Day 90	Number of subjects with SAEs during the study

Secondary Outcome Measures

Name	Time	Method
Efficacy: All Cause Mortality Rate at Day 90	Day 90	All cause mortality rate using Kaplan-Meier survival analysis
Number of Subjects Alive Without Organ Support at Day 90	Through Day 90	number of subjects alive and without organ support at the Day 90 visit
Safety and Tolerability: Proportion of Subjects With Adverse Events (AEs)	Continuous through Day 28	Proportion of subjects with adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Immunogenicity: Subjects With Rhu-pGSN Antibodies	Day 28	Number of subjects with rhu-pGSN antibodies at Day 28
Efficacy: Alive Without Support at Day 90	Day 90	Number of subjects Alive without organ support at Day 90
Safety and Tolerability: Proportion of Subjects With Drug-related Adverse Events (AEs)	Continuous through Day 14	Proportion of subjects with drug-related adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Trial Locations

Locations (3): Sant Joan de Reus SAM University Hospital
🇪🇸
Reus, Spain
Hospital Universitari de Tarragona Joan XXIII
🇪🇸
Tarragona, Spain
Spitalul Clinic de Boli Infecţioase şi Pneumoftiziologie
🇷🇴
Timişoara, Romania