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SHP656, a polysialylated recombinant factor VIII (PSA-rFVIII): First-in-human study evaluating safety, tolerability and pharmacokinetics in patients with severe haemophilia A

Tiede, Andreas, Allen, Geoffrey, Bauer, Alexander, Chowdary, Pratima, Collins, Peter, Goldstein, Brahm, Jiang, Hongyu Jeanne, Kock, Kathleen, Takács, István, Timofeeva, Margarita, Wolfsegger, Martin and Srivastava, Shouryadeep 2020. SHP656, a polysialylated recombinant factor VIII (PSA-rFVIII): First-in-human study evaluating safety, tolerability and pharmacokinetics in patients with severe haemophilia A. Haemophilia 26 (1) , pp. 47-55. 10.1111/hae.13878

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Abstract

Introduction SHP656 is the first factor VIII (FVIII) product developed using polysialylation (PSA) technology, in which full‐length recombinant (r) FVIII (anti‐haemophilic factor [recombinant]) is conjugated with a 20 kDa PSA polymer. Aim To compare the safety, immunogenicity and pharmacokinetics of SHP656 vs the parent rFVIII (octocog alfa) after single infusions of 25‐75 IU/kg in patients with severe haemophilia A (FVIII activity <1%). Methods Multinational, phase 1, prospective, open‐label, two‐period, fixed‐sequence, dose‐escalation trial (clinicaltrials.gov NCT02716194). Patients received single doses of rFVIII and then SHP656 sequentially at the same dose: 25 ± 3 IU/kg (Cohort 1), 50 ± 5 IU/kg (Cohort 2) and 75 ± 5 IU/kg (Cohort 3). Results Forty patients received rFVIII: 11 in Cohort 1, 16 in Cohort 2 and 13 in Cohort 3. Two patients withdrew before receiving SHP656, leaving 38 patients who completed the study and received both treatments. No treatment‐related adverse events (AEs), serious AEs, deaths, study withdrawals, thrombotic events or allergic reactions were reported; and no significant treatment‐related changes in laboratory parameters or vital signs. No patients developed FVIII inhibitors or antibodies to PSA. FVIII activity was significantly prolonged following SHP656 administration vs rFVIII with an approximately 1.5‐fold extension in mean residence time (P < .05). Exposure increased proportional to the SHP656 dose over the 25‐75 IU/kg dose range.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Wiley-Blackwell
ISSN: 1351-8216
Date of First Compliant Deposit: 2 January 2020
Date of Acceptance: 22 October 2019
Last Modified: 25 Mar 2020 12:32
URI: http://orca-mwe.cf.ac.uk/id/eprint/128129

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