NCT03466073

A Phase 1b/2a Study of the Safety and Pharmacokinetics of Rhu-plasma Gelsolin in Hospitalized Subjects With CAP

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
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 33 (actual)
• Sponsor: BioAegis Therapeutics Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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)

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 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: 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 mmol/L, Respiratory rate ≥30/min, 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, routine/standard 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 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.

Conditions

• Community-acquired Pneumonia

Interventions

Type	Name	Description
DRUG	Recombinant Human Plasma Gelsolin	Recombinant human plasma gelsolin lyophilized for reconstitution, reconstituted in sterile water
OTHER	Normal Saline Placebo	Normal saline in volume equivalent to drug

Timeline

• Start date: 2018-08-28
• Primary completion: 2019-04-02
• Completion: 2019-04-02
• First posted: 2018-03-15
• Last updated: 2020-01-27
• Results posted: 2020-01-27

Locations

8 sites across 2 countries: Australia, Georgia