A Phase 1/2 interventional study of Recombinant Human Plasma Gelsolin and Normal Saline Placebo in Community-acquired Pneumonia, sponsored by BioAegis Therapeutics Inc.. Completed at 8 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-01-27.
Sponsored by BioAegis Therapeutics Inc. · Phase 1/2, Interventional, and Treatment
A Phase 1b/2a, Double-blind, Placebo-controlled, Dose-escalation Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Recombinant Human Plasma gelsolin (rhu-pGSN) Added to Standard of Care in Subjects Hospitalized for Acute Community-acquired Pneumonia (CAP)
A total of 32 patients hospitalized with CAP will be randomized sequentially into 4 ascending dosing levels. Each dosing cohort will include 8 subjects randomized 3:1 rhu-pGSN:placebo (6 rhu-pGSN subjects:2 placebo subjects). Patient, caregiver, and sponsor will be blinded to treatment. An unblinded pharmacist will prepare the infusion, but otherwise have no contact with subject.
Dose will be based on actual body weight. Dose escalation will involve 3 dose levels of rhu-pGSN (6, 12, and 24 mg/kg) in patients admitted for CAP. Dose escalation will only occur after post-therapy safety information on all subjects in the prior cohort has been reviewed at Day 7 for the single-dose [SD] and multiple-ascending dose [MAD] arms. The MAD portion of the study will commence once single doses of 6 mg/kg of rhu-pGSN are shown to be acceptably safe. The first 2 doses must be administered in the hospital, but the third dose can be given in a monitored outpatient setting where appropriate. Discharged subjects will return for follow-up 7 days after the initiation of therapy (Day 7) and on Day 28 for the End-of-Study Visit.
To assess safety and tolerability starting at the initiation of study therapy, subjects will undergo physical examinations (PE; including vital sign measurements), adverse event (AE) assessments, concomitant medication assessments, safety laboratory testing, and electrocardiograms (EKG) completed locally, and other testing as per local custom.
Once informed consent is obtained, the following procedures will be performed:
Screening laboratory and other tests can serve as baseline values for participants (no need to repeat lab tests at entry if done within the prior 36 hours unless dictated by SOC).
Obtain repeat chest x-rays (CXRs), computed tomography (CT) scans, and labs/cultures, etc. during the hospitalization if/when indicated by SOC.
Recalculate CURB-65 and ΔSOFA scores and redraw procalcitonin, pGSN, and biomarker samples on Day 3 or 4 and Day 7.
For the one dose in the SD arm and the first 2 doses in the multiple-dose arms, blood will be drawn within 30 minutes predose, immediately postdose, and 2, 8, 12 and/or 16, and 24 hours (± 30 minutes) after the end of infusion for analysis of plasma for 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), and area under the curve from time zero to infinity (AUCinf). Sampling at both the 12- and 16-hour time points is encouraged where feasible, but only one of these two times is required. Identical PK sampling is encouraged where feasible, but not required for the third (last) dose.
On Day 28, collect samples for analysis of pGSN levels and antibodies against pGSN.
324 studies on the registry are indexed under Community-Acquired Pneumonia; 77 are open to participants now.
This study's enrollment of 33 is below the median of 250 across 195 interventional studies indexed under Community-Acquired Pneumonia.
Browse Community-Acquired Pneumonia studies →BioAegis Therapeutics Inc. is the lead sponsor of 5 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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 CAP:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CD4 count
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Intravenous administration of recombinant human plasma gelsolin at 6 mg/kg v. placebo (NSS) in addition to standard of care
Drug: Recombinant Human Plasma Gelsolin · Other: Normal Saline Placebo
Intravenous administration of recombinant human plasma gelsolin at 6 mg/kg once per day for 3 days v. placebo (NSS) in addition to standard of care
Drug: Recombinant Human Plasma Gelsolin · Other: Normal Saline Placebo
Intravenous administration of recombinant human plasma gelsolin at 12 mg/kg once per day for 3 days v. placebo (NSS) in addition to standard of care
Drug: Recombinant Human Plasma Gelsolin · Other: Normal Saline Placebo
Intravenous administration of recombinant human plasma gelsolin at 24 mg/kg once per day for 3 days v. placebo (NSS) in addition to standard of care
Drug: Recombinant Human Plasma Gelsolin · Other: Normal Saline Placebo
Recombinant human plasma gelsolin lyophilized for reconstitution, reconstituted in sterile water
Also known as: rhu-pGSN
Normal saline in volume equivalent to drug
Also known as: NSS (0.9% normal saline)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Treatment emergent adverse events were all adverse events (AEs) that occurred subsequent to enrollment. The seriousness of adverse events was judged by the site investigator.
Time frame: 0-28 days
Pharmacokinetics (PK) (Area Under the Rhu-pGSN Concentration - Time Curve)
Determine AUC 0-t area under the plasma concentration-time curve of rhu-pGSN from 0-24 hours on dosing days (estimated by subtracting pre-injection concentrations from the measured concentrations at each time point). In the single-dose arm, the subject was given only 1 dose so that data from later days were not obtained. In the multiple-dose arms, samples were obtained for each of the 3 doses.
Time frame: On Days 0-3, specimens were obtained just prior and immediately post dose and 2, 8,12 and/or 16 , and 24 hours post completion of IV administration. In the single-dose arm, only 1 dose was given and thus no data from later days were obtained.
Pharmacokinetics (PK) (Maximum Observed Rhu-pGSN Plasma Concentration (Cmax))
Maximum observed plasma concentration (Cmax) of rhu-pGSN in a 24 hours period after intravenous administration (estimated by subtracting pre-injection concentrations from the measured concentrations at each time point). For the 6 mg/kg dose, there were 4 evaluable subjects in the single-dose arm and 6 subjects in the multiple-dose arm at this dose, for a total of 10 evaluable subjects for Dose 1.
Time frame: On Days 0-3, specimens were obtained just prior and immediately post dose and 2, 8, 12 and/or 16, and 24 hours post completion of IV administration. In the single-dose arm, only 1 dose was given and thus no data from later days were obtained.
Number of Participants With Anti-pGSN Antibodies (Immunogenicity) at the End of Study (Day 28)
Number of participants who developed antibodies against pGSN at study day 28. Patients were first tested against less stringent screening criteria: if screen-positive, a stricter confirmatory test was performed; if screen-negative, no further immunogenicity testing was done.
Time frame: Day 28
Baseline and Sequential Severity Scores
CURB-65 (a 5 point score in which 1 point is allocated to the presence of each of the following: Confusion, Urea \>7 mmol/L, Respiratory rate ≥30 breaths min, Blood pressure systolic \<90 mmHg or diastolic ≤60 mmHg, and age ≥65 years); PSI (Pneumonia Severity Index, used to predict risk of morbidity and mortality and is classified in risk classes ranging from I to V from the lowest to highest risk as follows: Class I: PSI 0, class II: PSI 1-70, class III: PSI 71-90, class IV: PSI 91-130, class V: PSI \>130); SOFA (Sequential Organ Failure Assessment, measured based on 6 variables each representing an organ system scored from 0 to 4 each (normal to severe organ dysfunction/failure), and reported as the sum (range 0-24))
Time frame: Days 0-28
| Milestone | 6 mg/kg Rhu-pGSN Single Dose | Placebo Single Dose | 6 mg/kg Rhu-pGSN Multiple Ascending Dose | 12 mg/kg Rhu-pGSN Multiple Ascending Dose | 24 mg/kg Rhu-pGSN Multiple Ascending Dose | Placebo Multiple Ascending Dose |
|---|---|---|---|---|---|---|
| Started | 6 | 2 | 6 | 6 | 6 | 7 |
| Completed | 5 | 2 | 6 | 6 | 6 | 6 |
| Not completed | 1 | 0 | 0 | 0 | 0 | 1 |
| Withdrew: Death | 1 | 0 | 0 | 0 | 0 | 1 |
Treatment emergent adverse events were all adverse events (AEs) that occurred subsequent to enrollment. The seriousness of adverse events was judged by the site investigator.
| Participants | 6 mg/kg Rhu-pGSN Single Dose | Placebo Single Dose | 6 mg/kg Rhu-pGSN Multiple Ascending Dose | 12 mg/kg Rhu-pGSN Multiple Ascending Dose | 24 mg/kg Rhu-pGSN Multiple Ascending Dose | Placebo Multiple Ascending Dose |
|---|---|---|---|---|---|---|
| Subjects with at least 1 TEAE | 4 | 2 | 4 | 3 | 2 | 4 |
| Subjects with at least 1 Serious TEAE | 1 | 0 | 0 | 0 | 0 | 1 |
Determine AUC 0-t area under the plasma concentration-time curve of rhu-pGSN from 0-24 hours on dosing days (estimated by subtracting pre-injection concentrations from the measured concentrations at each time point). In the single-dose arm, the subject was given only 1 dose so that data from later days were not obtained. In the multiple-dose arms, samples were obtained for each of the 3 doses.
| µg*h/mL | 6 mg/kg Rhu-pGSN | 12 mg/kg Rhu-pGSN | 24 mg/kg Rhu-pGSN |
|---|---|---|---|
| AUC 0-t, Day 1 | 984.4 ± 3798.3 | 3450.1 ± 586.5 | 6911.3 ± 1914.1 |
| AUC 0-t, Day 2 | 674.3 ± 1062.4 | 2602.8 ± 755.3 | 1818.4 ± 4088.5 |
| AUC 0-t, Day 3 | 447.4 ± 626.6 | 3081.8 ± 1283.5 | 4315.8 ± 3004.3 |
Maximum observed plasma concentration (Cmax) of rhu-pGSN in a 24 hours period after intravenous administration (estimated by subtracting pre-injection concentrations from the measured concentrations at each time point). For the 6 mg/kg dose, there were 4 evaluable subjects in the single-dose arm and 6 subjects in the multiple-dose arm at this dose, for a total of 10 evaluable subjects for Dose 1.
| µg/mL | 6 mg/kg Rhu-pGSN | 12 mg/kg Rhu-pGSN | 24 mg/kg Rhu-pGSN |
|---|---|---|---|
| Cmax, Day 1 | 226.6 ± 393.3 | 291.9 ± 38.0 | 533.9 ± 139.9 |
| Cmax, Day 2 | 177.9 ± 128.4 | 292.0 ± 79.4 | 347.3 ± 274.7 |
| Cmax, Day 3 | 133.9 ± 86.0 | 320.6 ± 75.4 | 498.8 ± 275.3 |
Number of participants who developed antibodies against pGSN at study day 28. Patients were first tested against less stringent screening criteria: if screen-positive, a stricter confirmatory test was performed; if screen-negative, no further immunogenicity testing was done.
| Participants | 6 mg/kg Rhu-pGSN Single Dose | Placebo Single Dose | 6 mg/kg Rhu-pGSN Multiple Ascending Dose | 12 mg/kg Rhu-pGSN Multiple Ascending Dose | 24 mg/kg Rhu-pGSN Multiple Ascending Dose | Placebo Multiple Ascending Dose |
|---|---|---|---|---|---|---|
| Screened, positive | 0 | 0 | 1 | 2 | 6 | 2 |
| Confirmed, positive | 0 | 0 | 1 | 0 | 2 | 0 |
CURB-65 (a 5 point score in which 1 point is allocated to the presence of each of the following: Confusion, Urea \>7 mmol/L, Respiratory rate ≥30 breaths min, Blood pressure systolic \<90 mmHg or diastolic ≤60 mmHg, and age ≥65 years); PSI (Pneumonia Severity Index, used to predict risk of morbidity and mortality and is classified in risk classes ranging from I to V from the lowest to highest risk as follows: Class I: PSI 0, class II: PSI 1-70, class III: PSI 71-90, class IV: PSI 91-130, class V: PSI \>130); SOFA (Sequential Organ Failure Assessment, measured based on 6 variables each representing an organ system scored from 0 to 4 each (normal to severe organ dysfunction/failure), and reported as the sum (range 0-24))
| unitless | Combined Rhu-pGSN Multiple Ascending Dose | Combined Placebo Multiple Ascending Dose | 6 mg/kg Rhu-pGSN Single Dose | Placebo Single Dose |
|---|---|---|---|---|
| CURB-65-Baseline | 0 (0 to 2) | 1 (0 to 2) | 1 (0 to 2) | 1 (1 to 1) |
| Change in CURB-65 from Baseline to Day 28 | 0 (-1 to 1) | 0 (-1 to 0) | 0 (-1 to 2) | -0.5 (-1 to 0) |
| PSI score-Baseline | 52 (38 to 91) | 78 (56 to 98) | 67.5 (46 to 119) | 69 (62 to 76) |
| Change in PSI score from Baseline to Day 28 | 0 (-10 to 1) | -5 (-10 to 0) | 0 (0 to 0) | 0 (0 to 0) |
| SOFA score-Baseline | 1 (0 to 3) | 1 (0 to 4) | 1.5 (0 to 4) | 2 (2 to 2) |
| Change in SOFA score from Baseline to Day 28 | -1 (-3 to 0) | -1 (-4 to 0) | -1 (-1 to 0) | -2 (-2 to -2) |
Collected over 0-28 days. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 6 mg/kg Rhu-pGSN Single Dose | 1/6 (16.7%) | 1/6 (16.7%) | 3/6 (50%) |
| Placebo Single Dose | 0/2 (0%) | 0/2 (0%) | 2/2 (100%) |
| 6 mg/kg Rhu-pGSN Multiple Ascending Dose | 0/6 (0%) | 0/6 (0%) | 4/6 (66.7%) |
| 12 mg/kg Rhu-pGSN Multiple Ascending Dose | 0/6 (0%) | 0/6 (0%) | 3/6 (50%) |
| 24 mg/kg Rhu-pGSN Multiple Ascending Dose | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) |
| Placebo Multiple Ascending Dose | 1/7 (14.3%) | 1/7 (14.3%) | 4/7 (57.1%) |
| Event | 6 mg/kg Rhu-pGSN Single Dose | Placebo Single Dose | 6 mg/kg Rhu-pGSN Multiple Ascending Dose | 12 mg/kg Rhu-pGSN Multiple Ascending Dose | 24 mg/kg Rhu-pGSN Multiple Ascending Dose | Placebo Multiple Ascending Dose |
|---|---|---|---|---|---|---|
| PneumoniaInfections and infestations | 1/6 | 0/2 | 0/6 | 0/6 | 0/6 | 1/7 |
| Pulmonary EmbolismRespiratory, thoracic and mediastinal disorders | 0/6 | 0/2 | 0/6 | 0/6 | 0/6 | 1/7 |
| Event | 6 mg/kg Rhu-pGSN Single Dose | Placebo Single Dose | 6 mg/kg Rhu-pGSN Multiple Ascending Dose | 12 mg/kg Rhu-pGSN Multiple Ascending Dose | 24 mg/kg Rhu-pGSN Multiple Ascending Dose | Placebo Multiple Ascending Dose |
|---|---|---|---|---|---|---|
| DiarrheaGastrointestinal disorders | 0/6 | 1/2 | 0/6 | 0/6 | 0/6 | 0/7 |
| CellulitisInfections and infestations | 0/6 | 1/2 | 0/6 | 0/6 | 0/6 | 0/7 |
| Liver function test abnormalInvestigations | 0/6 | 1/2 | 0/6 | 0/6 | 0/6 | 0/7 |
| GoutMetabolism and nutrition disorders | 0/6 | 1/2 | 0/6 | 0/6 | 0/6 | 0/7 |
| NeuralgiaNervous system disorders | 0/6 | 1/2 | 0/6 | 0/6 | 0/6 | 0/7 |
| TachypneaRespiratory, thoracic and mediastinal disorders | 0/6 | 1/2 | 0/6 | 0/6 | 0/6 | 0/7 |
| Night sweatsSkin and subcutaneous tissue disorders | 0/6 | 1/2 | 0/6 | 0/6 | 0/6 | 0/7 |
| Rash maculo-papularSkin and subcutaneous tissue disorders | 0/6 | 1/2 | 0/6 | 0/6 | 0/6 | 0/7 |
| HypotensionVascular disorders | 1/6 | 1/2 | 0/6 | 0/6 | 0/6 | 1/7 |
| Blood pressure increasedInvestigations | 0/6 | 0/2 | 2/6 | 0/6 | 0/6 | 0/7 |
| Age, Continuous(years) | 6 mg/kg Rhu-pGSN Single Dose | Placebo Single Dose | 6 mg/kg Rhu-pGSN Multiple Ascending Dose | 12 mg/kg Rhu-pGSN Multiple Ascending Dose | 24 mg/kg Rhu-pGSN Multiple Ascending Dose | Placebo Multiple Ascending Dose | Total |
|---|---|---|---|---|---|---|---|
| Mean | 62.2 (35 to 81) | 64 (62 to 66) | 69.3 (56 to 83) | 55.3 (45 to 70) | 40 (22 to 66) | 64 (39 to 78) | 58.7 (22 to 83) |
| Sex: Female, Male(Participants) | 6 mg/kg Rhu-pGSN Single Dose | Placebo Single Dose | 6 mg/kg Rhu-pGSN Multiple Ascending Dose | 12 mg/kg Rhu-pGSN Multiple Ascending Dose | 24 mg/kg Rhu-pGSN Multiple Ascending Dose | Placebo Multiple Ascending Dose | Total |
|---|---|---|---|---|---|---|---|
| Female | 2 | 0 | 5 | 3 | 4 | 3 | 17 |
| Male | 4 | 2 | 1 | 3 | 2 | 4 | 16 |
| Race/Ethnicity, Customized(Participants) | 6 mg/kg Rhu-pGSN Single Dose | Placebo Single Dose | 6 mg/kg Rhu-pGSN Multiple Ascending Dose | 12 mg/kg Rhu-pGSN Multiple Ascending Dose | 24 mg/kg Rhu-pGSN Multiple Ascending Dose | Placebo Multiple Ascending Dose | Total |
|---|---|---|---|---|---|---|---|
| White | 6 | 2 | 6 | 6 | 6 | 7 | 33 |
| Region of Enrollment(Participants) | 6 mg/kg Rhu-pGSN Single Dose | Placebo Single Dose | 6 mg/kg Rhu-pGSN Multiple Ascending Dose | 12 mg/kg Rhu-pGSN Multiple Ascending Dose | 24 mg/kg Rhu-pGSN Multiple Ascending Dose | Placebo Multiple Ascending Dose | Total |
|---|---|---|---|---|---|---|---|
| Georgia | 1 | 1 | 6 | 6 | 6 | 7 | 27 |
| Australia | 5 | 1 | 0 | 0 | 0 | 0 | 6 |
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Studies of the drug tested here: Gelsolin
Community-Acquired Pneumonia →
BioAegis Therapeutics Inc.