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Rhu-pGSN for Severe Covid-19 Pneumonia

Primary Purpose

Sars-CoV2

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Recombinant human plasma gelsolin (Rhu-pGSN)

Placebo

About this trial

This is an interventional treatment trial for Sars-CoV2 focused on measuring COVID-19, Pneumonia, Severe, Cytokine storm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Spitalul Clinic de Boli Infecţioase şi Pneumoftiziologie
Sant Joan de Reus SAM University Hospital
Hospital Universitari de Tarragona Joan XXIII

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Rhu-pGSN

Arm Description

Normal saline in matched volume to treatment arm. Undistinguishable in syringe.

Recombinant human plasma gelsolin reconstituted for slow bolus injection.

Outcomes

Primary Outcome Measures

Efficacy: Proportion of Subjects Alive Not on Vasopressors, Mechanical Ventilator, and Dialysis

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 and Tolerability: Proportion of Subjects With Serious Adverse Events (SAEs)

Proportion of subjects with serious adverse events (SAEs) as judged by the investigator

Secondary Outcome Measures

Efficacy: Daily Change in the WHO 9-point Severity Score

Daily change in the 9-point Severity Score (ordinal scale) proposed by a special WHO committee for COVID-19 pneumonia where a score of 8 indicates death and 0 is no clinical or virological evidence of COVID-19 infection

Efficacy: All Cause Mortality Rate at Days 28 and 90

All cause mortality rate using Kaplan-Meier survival analysis

Efficacy: Proportion of Subjects Alive Without the 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 alive without the ongoing use of vasopressors, ongoing intubation/mechanical ventilation, ongoing residence in an intensive care unit, new ongoing need for dialysis/renal replacement therapy

Efficacy: Proportion of Subjects Discharged to Home or Immediate Prior Residence

Proportion of subjects discharged to home or immediate prior residence

Efficacy: Length of Stay (LOS) of Surviving Subjects in the Hospital and in ICU

LOS of surviving subjects in the hospital and in ICU

Efficacy: Proportion of Subjects Readmitted to the Hospital

Proportion of subjects readmitted to the hospital

Safety and Tolerability: Proportion of Subjects With Adverse Events (AEs)

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

Safety and Tolerability: Proportion of Subjects With New or Worsening Clinically Significant Laboratory Abnormalities

Proportion of subjects with new or worsening clinically significant laboratory abnormalities

Immunogenicity: Proportion of Subjects With Rhu-pGSN Antibodies

Proportion of subjects with rhu-pGSN antibodies

Pharmacokinetics: Maximum Concentration (C Max) of Added Rhu-pGSN

Blood samples for dose #1 will be collected 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).

Pharmacokinetics: Time to Maximum Concentration (T Max) of Added Rhu-pGSN

Pharmacokinetics: Half-life (T 1/2) of Added Rhu-pGSN

Pharmacokinetics: Area Under the Curve From Time 0 to 8 Hours (AUC 0-8) of Added Rhu-pGSN

Pharmacokinetics: Area Under the Curve From Time 0 to Infinity (AUC 0-inf) of Added Rhu-pGSN

Full Information

NCT ID

NCT04358406

First Posted

April 16, 2020

Last Updated

January 25, 2023

Sponsor

BioAegis Therapeutics Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04358406

Brief Title

Rhu-pGSN for Severe Covid-19 Pneumonia

Official Title

A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Proof-Of-Concept Study To Evaluate Efficacy And Safety Of Recombinant Human Plasma Gelsolin (Rhu-pGSN) Added To Standard Of Care In Subjects With Severe Covid-19 Pneumonia

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

July 30, 2020 (Actual)

Primary Completion Date

May 25, 2021 (Actual)

Study Completion Date

January 28, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

BioAegis Therapeutics Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sars-CoV2

Keywords

COVID-19, Pneumonia, Severe, Cytokine storm

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Randomized, blinded, placebo controlled interventional

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Treatment blinded to all but unblinded pharmacist

Allocation

Randomized

Enrollment

64 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Normal saline in matched volume to treatment arm. Undistinguishable in syringe.

Arm Title

Rhu-pGSN

Arm Type

Active Comparator

Arm Description

Recombinant human plasma gelsolin reconstituted for slow bolus injection.

Intervention Type

Drug

Intervention Name(s)

Recombinant human plasma gelsolin (Rhu-pGSN)

Other Intervention Name(s)

gelsolin

Intervention Description

Intravenous administration of rhu-pGSN at 12 mg/kg, 3 doses

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Normal saline in matched volume to treatment arm. Undistinguishable in syringe.

Primary Outcome Measure Information:

Title

Efficacy: Proportion of Subjects Alive Not on Vasopressors, Mechanical Ventilator, and Dialysis

Description

Time Frame

Day 14

Title

Safety and Tolerability: Proportion of Subjects With Serious Adverse Events (SAEs)

Description

Proportion of subjects with serious adverse events (SAEs) as judged by the investigator

Time Frame

Continuous through Day 28

Secondary Outcome Measure Information:

Title

Efficacy: Daily Change in the WHO 9-point Severity Score

Description

Time Frame

Daily through at least Day 14

Title

Efficacy: All Cause Mortality Rate at Days 28 and 90

Description

All cause mortality rate using Kaplan-Meier survival analysis

Time Frame

At Days 28 and 90

Title

Description

Time Frame

Days 7, 28, 60, and 90

Title

Efficacy: Proportion of Subjects Discharged to Home or Immediate Prior Residence

Description

Proportion of subjects discharged to home or immediate prior residence

Time Frame

Continuous through Day 28

Title

Efficacy: Length of Stay (LOS) of Surviving Subjects in the Hospital and in ICU

Description

LOS of surviving subjects in the hospital and in ICU

Time Frame

Continuous through day 28

Title

Efficacy: Proportion of Subjects Readmitted to the Hospital

Description

Proportion of subjects readmitted to the hospital

Time Frame

Up to 90 days

Title

Safety and Tolerability: Proportion of Subjects With Adverse Events (AEs)

Description

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

Time Frame

Continuous through Day 28

Title

Safety and Tolerability: Proportion of Subjects With New or Worsening Clinically Significant Laboratory Abnormalities

Description

Proportion of subjects with new or worsening clinically significant laboratory abnormalities

Time Frame

Continuous through Day 28

Title

Immunogenicity: Proportion of Subjects With Rhu-pGSN Antibodies

Description

Proportion of subjects with rhu-pGSN antibodies

Time Frame

Days 1, 28, and 90

Title

Pharmacokinetics: Maximum Concentration (C Max) of Added Rhu-pGSN

Description

Time Frame

Continuous through day 3

Title

Pharmacokinetics: Time to Maximum Concentration (T Max) of Added Rhu-pGSN

Description

Time Frame

Continuous through day 3

Title

Pharmacokinetics: Half-life (T 1/2) of Added Rhu-pGSN

Description

Time Frame

Continuous through day 3

Title

Pharmacokinetics: Area Under the Curve From Time 0 to 8 Hours (AUC 0-8) of Added Rhu-pGSN

Description

Time Frame

Continuous through day 3

Title

Pharmacokinetics: Area Under the Curve From Time 0 to Infinity (AUC 0-inf) of Added Rhu-pGSN

Description

Time Frame

Continuous through day 3

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mark J DiNubile, MD

Organizational Affiliation

BioAegis Therapeutics Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Spitalul Clinic de Boli Infecţioase şi Pneumoftiziologie

City

Timişoara

Country

Romania

Facility Name

Sant Joan de Reus SAM University Hospital

City

Reus

Country

Spain

Facility Name

Hospital Universitari de Tarragona Joan XXIII

City

Tarragona

Country

Spain

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Rhu-pGSN for Severe Covid-19 Pneumonia

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