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

Christof Geisen; Erika Fleck; Stephan Martin Gastón Schäfer; Carmen Walter; Susanne Braeuninger; Jens Søndergaard Jensen; Douglas Sheridan; Kiran Patki; Róisín Armstrong; Bjørn Skogen; Frank Behrens; Erhard Seifried; Jens Kjeldsen-Kragh; Mette Kjær; Michaela Köhm

doi:10.1055/a-2398-9344

Thrombosis and Haemostasis, Inhaltsverzeichnis

CC BY-NC-ND 4.0 · Thromb Haemost 2025; 125(04): 352-363
DOI: 10.1055/a-2398-9344

New Technologies, Diagnostic Tools and Drugs

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

Christof Geisen

¹Institute of Transfusion Medicine and Immunohaematology, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen GmbH, Frankfurt am Main, Germany

,

Erika Fleck

¹Institute of Transfusion Medicine and Immunohaematology, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen GmbH, Frankfurt am Main, Germany

,

Stephan Martin Gastón Schäfer

²Division Clinical Research, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany

,

Carmen Walter

²Division Clinical Research, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany

,

Susanne Braeuninger

¹Institute of Transfusion Medicine and Immunohaematology, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen GmbH, Frankfurt am Main, Germany

,

Jens Søndergaard Jensen

³Aixial Danmark A/S, Herlev, Denmark

,

Douglas Sheridan

⁴Rallybio, New Haven, Connecticut, United States

,

Kiran Patki

⁴Rallybio, New Haven, Connecticut, United States

,

Róisín Armstrong

⁴Rallybio, New Haven, Connecticut, United States

,

Bjørn Skogen

⁵Department of Laboratory Medicine, University Hospital of North Norway, Tromsø, Norway

,

Frank Behrens

²Division Clinical Research, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany

⁶Division of Rheumatology, University Hospital Goethe-University Frankfurt am Main, Germany

⁷Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Frankfurt am Main, Germany

,

Erhard Seifried

¹Institute of Transfusion Medicine and Immunohaematology, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen GmbH, Frankfurt am Main, Germany

,

Jens Kjeldsen-Kragh

⁵Department of Laboratory Medicine, University Hospital of North Norway, Tromsø, Norway

⁸Department of Clinical Immunology and Transfusion Medicine, Office for Medical Services, Region Skåne, Lund, Sweden

,

Mette Kjær^*

⁹Faculty of Health Sciences, UiT—The Arctic University of Norway, Hammerfest, Norway

¹⁰Finnmark Hospital Trust, Hammerfest, Norway

,

Michaela Köhm^*

²Division Clinical Research, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany

⁶Division of Rheumatology, University Hospital Goethe-University Frankfurt am Main, Germany

⁷Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Frankfurt am Main, Germany

› Institutsangaben

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

Volltext

Referenzen

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