Ignite Creation Date:
2024-05-06 @ 11:13 AM
Last Modification Date:
2024-10-26 @ 12:42 PM
Study NCT ID:
NCT03466073
Status:
COMPLETED
Last Update Posted:
2020-01-27
First Post:
2018-03-02
Brief Title:
A Phase 1b2a Study of the Safety and Pharmacokinetics of Rhu-plasma Gelsolin in Hospitalized Subjects With CAP
Sponsor:
BioAegis Therapeutics Inc
Organization:
BioAegis Therapeutics Inc
Study Overview
Official Title:
A Double-blind Placebo-controlled Dose-escalation Study of the Safety Pharmacokinetics and Pharmacodynamics of Recombinant Human Plasma Gelsolin Added to Standard of Care in Subjects Hospitalized for Acute Community-acquired Pneumonia
Status:
COMPLETED
Status Verified Date:
2020-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
A Phase 1b2a 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
Detailed Description:
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 31 rhu-pGSNplacebo 6 rhu-pGSN subjects2 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 mgkg 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 mgkg 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
1 Randomize to currently enrolling treatment arm
2 Perform PE and document radiographic evidence of pneumonia if not previously completed in preceding 36 hours calculate Confusion Urea 7 mmolL Respiratory rate 30min Blood pressure systolic 90 or diastolic 60 and age 65 years CURB-65 Sequential Organ Failure Assessment SOFA and Pneumonia Severity Index PSI scores
3 Obtain blood and sputum cultures routinestandard labs and EKG per standard of care SOC if not already performed The microbiology lab is encouraged to also perform sputum Gram-stains antigen detection immunoassay and genomic diagnostic tests when available
4 Draw blood for baseline pGSN levels C-reactive protein CRP procalcitonin level and 10 ml aliquot to be frozen for subsequent biomarker assays
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 labscultures etc during the hospitalization ifwhen 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 andor 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 T12 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
Dose will be based on actual body weight Dose escalation will involve 3 dose levels of rhu-pGSN 6 12 and 24 mgkg 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 mgkg 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
1 Randomize to currently enrolling treatment arm
2 Perform PE and document radiographic evidence of pneumonia if not previously completed in preceding 36 hours calculate Confusion Urea 7 mmolL Respiratory rate 30min Blood pressure systolic 90 or diastolic 60 and age 65 years CURB-65 Sequential Organ Failure Assessment SOFA and Pneumonia Severity Index PSI scores
3 Obtain blood and sputum cultures routinestandard labs and EKG per standard of care SOC if not already performed The microbiology lab is encouraged to also perform sputum Gram-stains antigen detection immunoassay and genomic diagnostic tests when available
4 Draw blood for baseline pGSN levels C-reactive protein CRP procalcitonin level and 10 ml aliquot to be frozen for subsequent biomarker assays
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 labscultures etc during the hospitalization ifwhen 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 andor 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 T12 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None