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.

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.
Competing Interests: Declaration of competing interests M.Kj., B.S., and J.KK. are stockholders of Prophylix AS, a Norwegian biotech company, which produced the study drug. M.Kj. and J.KK. are currently consultants for Rallybio, which is the sponsor of the study. R.A. and Z.B. are employees of Rallybio. J.KK. also provides consultancy services for ROS Therapeutics, Glycorex Transplantation AB, and Johnson & Johnson. German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH has a contract with Rallybio for the present study. The remaining authors declare no competing financial interests.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)