A Phase 1b PK/PD Study to Demonstrate Antigen Elimination with RLYB212, A Monoclonal Anti-HPA-1a Antibody for FNAIT Prevention

Abstract

Background

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare bleeding disorder of the fetus/newborn caused by development of maternal alloantibodies against fetal human platelet antigens (HPAs), predominantly HPA-1a. Currently there are no treatments available to prevent maternal alloimmunization to HPAs or FNAIT.

Methods

This proof-of-concept study (EudraCT Number: 2021-005380-49) was designed to assess the ability of subcutaneous (SC) RLYB212, a monoclonal anti-HPA-1a antibody, to eliminate HPA-1a-positive platelets in an antigen challenge model of a 30 mL fetal–maternal hemorrhage. Subjects were randomized to receive a single SC dose of RLYB212 or placebo on day 1 in a single-blinded manner, followed by transfusion of 10 × 10⁹ HPA-1a-positive platelets on day 8.

Results

Four subjects received 0.09 mg SC RLYB212, five received 0.29 mg SC RLYB212, and two received placebo. RLYB212 achieved rapid elimination of HPA-1a-positive platelets in a concentration-dependent manner, with concentrations as low as 3.57 ng/mL meeting the prespecified proof-of-concept criterion of ≥90% reduction in platelet elimination half-life versus placebo. Following HPA-1a-positive platelet transfusion, a rapid decline was observed in the concentration of RLYB212 over a period of 2 to 24 hours, corresponding to the time needed for RLYB212 to bind to ∼10% of HPA-1a on cell surfaces. RLYB212 was well tolerated with no reports of drug-related adverse events.

Conclusion

The data from this study are consistent with preclinical efficacy data and support the potential use of RLYB212 as a prophylactic treatment for FNAIT that prevents maternal HPA-1a alloimmunization during at-risk pregnancies.

Keywords

alloimmunization - HPA-1a - fetal and neonatal alloimmune thrombocytopenia - prophylaxis - RLYB212

Data Availability Statement

Proposals for access to deidentified individual subject data should be sent to [e-mail].

Authors' Contribution

D.S., K.P., and R.A. conceptualized the study and wrote the first draft of the study protocol. The protocol was finalized by Rallybio after being reviewed by C.G., S.M.G.S., C.W., J.S.J., F.B., J.K.-K., M.Kj., and M.Ko., and before submission to the Ethics Committee at Frankfurt University Hospital and the Paul-Ehrlich-Institut. C.G., E.F., J.K.-K., and M.Kj. validated the method for determining transfused platelets; E.F. performed the flow cytometry analyses; and C.G., E.F., J.K.-K., and M.Kj. approved all the flow cytometry plots before entry into the study database. M.Ko. was the principal investigator of the study. C.G. and E.F. performed the selection of platelet concentrates. C.G., E.F., S.M.G.S., C.W., S.B., F.B., and M.Ko. recruited and/or screened study participants. S.M.G.S., F.B., and M.Ko. performed administration of study drug, administration of platelets, and surveillance of study participants. Data were interpreted by C.G., S.M.G.S., C.W., J.S.J., D.S., K.P., R.A., B.S., F.B., E.S., J.K.-K., M.Kj., and M.Ko. Statistical analyses were performed by J.S.J. The manuscript was prepared by C.G., J.S.J., D.S., K.P., R.A., and J.K.-K., with medical writing support provided by Chameleon Communications International, Ltd (funded by Rallybio IPA, LLC). E.F., S.M.G.S., C.W., S.B., B.S., F.B., E.S., M.Kj., and M.Ko. reviewed and revised the manuscript. All authors approved the final manuscript.

Publikationsverlauf

Eingereicht: 14. Juni 2024

Angenommen: 17. August 2024

Accepted Manuscript online:
21. August 2024

Artikel online veröffentlicht:
12. September 2024

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