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dc.contributor.authorGeisen, Christof
dc.contributor.authorKjær, Mette
dc.contributor.authorFleck, Erika
dc.contributor.authorSkogen, Bjørn
dc.contributor.authorArmstrong, Roisin
dc.contributor.authorBehrens, Frank
dc.contributor.authorBhagwagar, Zubin
dc.contributor.authorBraeuninger, Susanne
dc.contributor.authorMörtberg, Anette
dc.contributor.authorOlsen, Klaus Juel
dc.contributor.authorScafer, Stephan Martin Gaston
dc.contributor.authorWalter, Carmen
dc.contributor.authorSeifried, Erhard
dc.contributor.authorWikman, Agneta
dc.contributor.authorKjeldsen-Kragh, Jens
dc.contributor.authorKoehm, Michaela
dc.date.accessioned2023-02-14T08:06:35Z
dc.date.available2023-02-14T08:06:35Z
dc.date.issued2022-12-22
dc.description.abstractBackground: Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a rare and potentially life-threatening bleeding disorder of the fetus/newborn. Antibodies against human platelet antigen 1a (HPA-1a) are associated with the most frequent FNAIT cases. There are no approved therapies for FNAIT prevention or treatment. RLYB211 is a polyclonal HPA-1a hyperimmune IgG being developed to prevent FNAIT. Objectives: To investigate whether a single dose of anti–HPA-1a (1000 IU) could markedly accelerate the elimination of HPA-1ab platelets transfused into healthy, HPA1a–negative participants as compared with placebo.<p> <p>Methods: This randomized, single-blind, placebo–controlled, single-center, phase 1/2 proof-of-concept study (EudraCT: 2019-003459-12) included HPA-1a– and HLA-A2– negative healthy men. Cohort 1 received intravenous RLYB211 or placebo 1 hour after transfusion of HPA-1ab platelets. Cohort 1B received RLYB211 or placebo, followed by platelet transfusion 1 week later. Primary endpoint was the half-life of transfused platelets in circulation after administration of RLYB211 or placebo, determined by flow cytometry. Proof of concept was ≥90% reduction of half-life relative to placebo. <p>Results: Twelve participants were allocated to cohort 1 or 1B and randomized to receive RLYB211 (n = 9) or placebo (n = 3). RLYB211 markedly accelerated the elimination of HPA-1ab platelets in all participants vs placebo. In cohort 1B, this effect was observed 7 days after RLYB211 administration. Two treatment–emergent adverse events were possibly related to treatment, both in RLYB211–treated participants. No participants developed HPA-1a antibodies at 12 or 24 weeks. <p>Conclusion: These data support the hypothesis that anti–HPA-1a could be used as prophylaxis in women at risk of having an FNAIT–affected pregnancy.en_US
dc.identifier.citationGeisen C, Kjær MK, Fleck, Skogen br, Armstrong, Behrens F, Bhagwagar Z, Braeuninger, Mörtberg A, Olsen KJ, Scafer, Walter, Seifried E, Wikman A, Kjeldsen-Kragh J, Koehm. An HPA-1a-positive platelet-depleting agent for prevention of fetal and neonatal alloimmune thrombocytopenia: a randomized, single-blind, placebo-controlled, single-center, phase 1/2 proof-of-concept study. Journal of Thrombosis and Haemostasis. 2022en_US
dc.identifier.cristinIDFRIDAID 2121900
dc.identifier.doi10.1016/j.jtha.2022.11.041
dc.identifier.issn1538-7933
dc.identifier.issn1538-7836
dc.identifier.urihttps://hdl.handle.net/10037/28546
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalJournal of Thrombosis and Haemostasis
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleAn HPA-1a-positive platelet-depleting agent for prevention of fetal and neonatal alloimmune thrombocytopenia: a randomized, single-blind, placebo-controlled, single-center, phase 1/2 proof-of-concept studyen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)