PL6-SN-08 - Spray-dried Plasma: A Multi-center, Prospective, Randomized, Dose-escalation Cohort Safety Clinical Trial

Background/Case Studies: Plasma transfused pre-hospital to patients at risk for hemorrhagic shock has been shown to reduce mortality. Cold chain, manufacturing and logistical challenges have limited the availability of this life-saving product. Currently available dried plasma products are packaged in glass bottles, which are not ideal for pre-hospital settings.  A new spray-dried plasma, Frontline On-Demand Plasma (ODP), has been developed and is packaged in a plastic bag. This study reports the results of a first-in-human dose-escalation clinical trial evaluating this product.

Study

Design/Methods: Twenty-four healthy volunteers were sequentially enrolled into three dose-escalation cohorts, with a partial double-blind crossover arm in Cohort 3. All plasma used was autologous, collected via apheresis (600-840 mL donations, up to 4 times).  Infusions took place at 2 clinical sites. Plasma was initially processed into PF24, with half of each collection further processed into ODP. Cohort 1 (n=6) received a single unit open-label infusion of 200 mL ODP; Cohort 2 (n=6) received a two-unit open-label infusions of 400 mL ODP; and Cohort 3 (n=12) was randomized to receive 800 mL (4 units) of PF24 and 4 units of ODP in a partial, randomized, double-blind crossover design, with a 14-day washout period between infusions. Subjects were monitored for 28 days after each infusion. The primary outcome was treatment-emergent adverse events (TEAEs).

Results/Findings: All 24 subjects completed the study, and all infusions were well tolerated. A total of 66 ODP units were manufactured with no unit breakage. In Cohort 3 there were 26 adverse events, 21 of which were TEAEs and all of which were determined to be unrelated or unlikely related to study product.  There were no SAEs.  The most common TEAE was headache, with no clear temporal relationship to infusion and occurring at equal frequency in both ODP and PF24 arms.  Minor elevations in protein C, protein S, thrombin-antithrombin complexes, and prothrombin fragment 1+2 levels were observed, but none were considered clinically significant. Minimal D-dimer elevations (less than 2.1 ug/mL) occurred in 7 subjects, without clinical signs of thromboembolic events or clear association with ODP versus PF24.  Out-of-range values for specialized coagulation tests were observed equally in both groups.

Conclusions: This multi-center, dose-escalation clinical trial demonstrated that spray-dried plasma (Frontline ODP) is comparable in safety and potency to standard frozen plasma. No thromboembolic events were observed. The product's compressible plastic packaging and ease of reconstitution may enable faster preparation and use in resuscitation of bleeding patients.