PB0333 - High-concentration protein C concentrate: in vitro and in vivo feasibility studies

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

PL

Peter Leidenmuehler

Lead, Toxicology and Nonclinical Submissions, PDT Clinical and Translational Sciences
Baxalta Innovations GmbH, a Takeda company, Vienna, Austria
Vienna, Wien, Austria

Co-Author(s)

AK

Alexandra N. Kopić

Strategist, Nonclinical Development, PDT Clinical and Translational Sciences
Baxalta Innovations GmbH, a Takeda company, Vienna, Austria
Vienna, Wien, Austria
AC

Alessandra Maria Casano

Manager, Biomarker and Bioanalytics, PDT Clinical and Translational Sciences
Baxalta Innovations GmbH, a Takeda company, Vienna, Austria
Vienna, Wien, Austria
MW

Markus Weiller

Director, Translational Science, PDT Clinical and Translational Sciences
Baxalta Innovations GmbH, a Takeda company, Vienna, Austria
Vienna, Wien, Austria
GB

Gerald Brachtl

Research Investigator, PDT Formulation Development
Baxalta Innovations GmbH, a Takeda company, Vienna, Austria
Vienna, Wien, Austria
SH

Stefanie Hosiner

Research Investigator, PDT Formulation Development
Baxalta Innovations GmbH, a Takeda company, Vienna, Austria
Vienna, Wien, Austria
JH

Joris Hoefinghoff

Head, PDT Formulation Development
Baxalta Innovations GmbH, a Takeda company, Vienna, Austria
Vienna, Wien, Austria
BJ

Bettina Janesch

Scientist, PDT Formulation Development
Baxalta Innovations GmbH, a Takeda company, Vienna, Austria
Vienna, Wien, Austria

Presenting Author(s)

HS

Henrik Sliwka

Background: Protein C concentrate (human) (PC; Baxalta Inc., a Takeda company) is currently only approved for intravenous (IV) administration; however, off-label subcutaneous (SC) use has also been reported. It is anticipated that SC administration requires increased doses versus the IV route, highlighting the potential need for PC administration at an increased concentration in a reduced volume.

Aims: To determine the feasibility of reconstituting PC in a 50% reduced volume, and the associated in vivo safety and pharmacokinetics.

Methods: Vials of PC (1000 IU) were reconstituted in either 10 mL (standard volume) or 5 mL (50% reduced volume) sterile water. The quality of all samples was measured against the acceptance criteria for PC reconstituted in the standard volume (n=3 vials per volume). Sample stability at room temperature was also investigated up to 24 hours following reconstitution. In vivo assessments of PC SC and IV administration were performed in Göttingen minipigs (SC: n=2 per sex per volume; IV: standard volume, n=2 per sex). This study was funded by Baxalta Innovations GmbH, a Takeda company.

Results: All PC samples complied with acceptance criteria for visual appearance, reconstitution time, pH and osmolality (Table 1). When reconstituted in a 50% reduced volume, mean PC values for protein C activity, protein content, sodium chloride content and sodium citrate content were approximately double those of PC reconstituted in the standard volume. Storing samples at room temperature for up to 24 hours did not negatively affect product quality. Data from Göttingen minipigs indicated no adverse clinical signs following SC administration of PC in a 50% reduced volume. Plasma PC concentrations were comparable between standard and reduced volume.

Conclusion(s): Our in vitro data indicate that reconstitution of PC in a 50% reduced volume does not negatively impact product quality. In vivo data support the potential for PC SC administration in the reduced volume.