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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

Geisen, Christof ; Kjaer, Mette ; Fleck, Erika ; Skogen, Bjorn ; Armstrong, Róisín ; Behrens, Frank ; Bhagwagar, Zubin ; Braeuninger, Susanne ; Mortberg, Anette and Olsen, Klaus Juel , et al. (2023) In Journal of Thrombosis and Haemostasis 21(4). p.838-849
Abstract

Background: 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, HPA-1a–negative participants as compared with placebo. Methods: This randomized, single-blind, placebo–controlled, single-center, phase 1/2 proof-of-concept study (EudraCT:... (More)

Background: 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, HPA-1a–negative participants as compared with placebo. 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. 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. 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.

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type
Contribution to journal
publication status
published
subject
keywords
alloantibodies, human platelet antigen, intracranial hemorrhage, neonatal alloimmune thrombocytopenia, prophylaxis
in
Journal of Thrombosis and Haemostasis
volume
21
issue
4
pages
12 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:85150968042
  • pmid:36696185
ISSN
1538-7933
DOI
10.1016/j.jtha.2022.11.041
language
English
LU publication?
yes
id
88156936-a046-4690-ae61-27900ce5c816
date added to LUP
2023-05-22 13:37:01
date last changed
2024-06-15 03:07:58
@article{88156936-a046-4690-ae61-27900ce5c816,
  abstract     = {{<p>Background: 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, HPA-1a–negative participants as compared with placebo. 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. 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. 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.</p>}},
  author       = {{Geisen, Christof and Kjaer, Mette and Fleck, Erika and Skogen, Bjorn and Armstrong, Róisín and Behrens, Frank and Bhagwagar, Zubin and Braeuninger, Susanne and Mortberg, Anette and Olsen, Klaus Juel and Gastón Schäfer, Stephan Martin and Walter, Carmen and Seifried, Erhard and Wikman, Agneta and Kjeldsen-Kragh, Jens and Koehm, Michaela}},
  issn         = {{1538-7933}},
  keywords     = {{alloantibodies; human platelet antigen; intracranial hemorrhage; neonatal alloimmune thrombocytopenia; prophylaxis}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{838--849}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Thrombosis and Haemostasis}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1016/j.jtha.2022.11.041}},
  doi          = {{10.1016/j.jtha.2022.11.041}},
  volume       = {{21}},
  year         = {{2023}},
}