Sars-CoV2Phase 2NCT04358406
Rhu-pGSN for Severe Covid-19 Pneumonia
A Phase 2 study testing Recombinant human plasma gelsolin (Rhu-pGSN) in people with Sars-CoV2, run by BioAegis Therapeutics Inc. at 3 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sars-CoV2
- What is being tested?
- Recombinant human plasma gelsolin (Rhu-pGSN)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 30 Jul 2020to 28 Jan 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 20Show fewer
- 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)
Who cannot join
- 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
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Spain2 sites
Sant Joan de Reus SAM University Hospital
Reus
Hospital Universitari de Tarragona Joan XXIII
Tarragona
Romania1 site
Spitalul Clinic de Boli Infecţioase şi Pneumoftiziologie
Timișoara
About this study
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 Objectives:
Primary
Read more
- 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
Read the 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.
- Conditions
- Sars-CoV2
- Being tested
- Recombinant human plasma gelsolin (Rhu-pGSN), Placebo
- Keywords
- COVID-19, Pneumonia, Severe, Cytokine storm
- Medical subject headings
- COVID-19, Pneumonia, Lymphoma, Follicular, Cytokine Release Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant human plasma gelsolin (Rhu-pGSN)Drug
Also called gelsolin
Intravenous administration of rhu-pGSN at 12 mg/kg, 3 doses
PlaceboOther
Normal saline in matched volume to treatment arm. Undistinguishable in syringe.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Normal saline in matched volume to treatment arm. Undistinguishable in syringe. Receives: Other: Placebo |
| Rhu-pGSN | Active comparator | Recombinant human plasma gelsolin reconstituted for slow bolus injection. Receives: Drug: Recombinant human plasma gelsolin (Rhu-pGSN) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy: Proportion of Subjects Alive Not on Vasopressors, Mechanical Ventilator, or 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).
Measured: Day 14
Safety: Number of Subjects With SAEs
Number of subjects with SAEs during the study
Measured: Day 1 through Day 90
Secondary outcomes (6)
Efficacy: All Cause Mortality Rate at Day 90
All cause mortality rate using Kaplan-Meier survival analysis
Measured: Day 90
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
Measured: Continuous through Day 28
Immunogenicity: Subjects With Rhu-pGSN Antibodies
Number of subjects with rhu-pGSN antibodies at Day 28
Measured: Day 28
Efficacy: Alive Without Support at Day 90
Number of subjects Alive without organ support at Day 90
Measured: Day 90
Safety and Tolerability: Proportion of Subjects With Drug-related Adverse Events (AEs)
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
Measured: Continuous through Day 14
Number of Subjects Alive Without Organ Support at Day 90
number of subjects alive and without organ support at the Day 90 visit
Measured: Through Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2020
- Study start30 Jul 2020
- Primary completion25 May 2021
- Study completion28 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Sars-CoV2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- Randomized, blinded, placebo controlled interventional
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioAegis Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mark J DiNubile, MD, Study director, BioAegis Therapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04358406
- Sponsor's protocol ID
- BTI-202
- Status last verified
- Sep 2023
- First submitted
- 16 Apr 2020
- Last updated
- 28 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04358406
- Acronym / sponsor ID
- BTI-202
- Conditions
- Sars-CoV2
- Keywords
- COVID-19, Pneumonia, Severe, Cytokine storm
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- BioAegis Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 30 Jul 2020 (actual)
- Primary completion
- 25 May 2021 (actual)
- Study completion
- 28 Jan 2022 (actual)
- First posted
- 24 Apr 2020 (actual)
- Results
- Posted 9 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, blinded, placebo controlled interventional
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboNormal saline in matched volume to treatment arm. Undistinguishable in syringe. |
| Rhu-pGSN | Active comparator | Drug: Recombinant human plasma gelsolin (Rhu-pGSN)Recombinant human plasma gelsolin reconstituted for slow bolus injection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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:
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Recombinant human plasma gelsolin (Rhu-pGSN)Also: gelsolinIntravenous administration of rhu-pGSN at 12 mg/kg, 3 doses | Drug | Rhu-pGSN |
| PlaceboNormal saline in matched volume to treatment arm. Undistinguishable in syringe. | Other | Placebo |
Primary outcome
Efficacy: Proportion of Subjects Alive Not on Vasopressors, Mechanical Ventilator, or Dialysis
Time frame: 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
Time frame: Day 1 through Day 90
Number of subjects with SAEs during the study
6 secondary outcomes
Efficacy: All Cause Mortality Rate at Day 90
Time frame: Day 90
Safety and Tolerability: Proportion of Subjects With Adverse Events (AEs)
Time frame: Continuous through Day 28
Immunogenicity: Subjects With Rhu-pGSN Antibodies
Time frame: Day 28
Efficacy: Alive Without Support at Day 90
Time frame: Day 90
Safety and Tolerability: Proportion of Subjects With Drug-related Adverse Events (AEs)
Time frame: Continuous through Day 14
Number of Subjects Alive Without Organ Support at Day 90
Time frame: Through Day 90
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark J DiNubile, MD study director
BioAegis Therapeutics Inc.
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Recombinant human plasma gelsolin (Rhu-pGSN) in people with Sars-CoV2, run by BioAegis Therapeutics Inc. at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain, Romania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy: Proportion of Subjects Alive Not on Vasopressors, Mechanical Ventilator, or Dialysis (time frame: Day 14). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2023.