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CC BY 4.0 · Am J Perinatol
DOI: 10.1055/a-2666-5642
Original Article

Design of a Phase 3, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of Nipocalimab in Pregnancies at Risk for Fetal and Neonatal Alloimmune Thrombocytopenia

Authors

  • Heidi Tiller 

    1   Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
    2   Department of Obstetrics and Gynecology, University Hospital of North Norway, Tromsø, Norway

  • Eleonor Tiblad

    3   Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden

  • Pamela Baker

    4   Johnson & Johnson, Spring House, Pennsylvania

  • Hillary Van Valkenburgh

    4   Johnson & Johnson, Spring House, Pennsylvania

  • Dirk Heerwegh

    5   Johnson & Johnson, Beerse, Belgium

  • Babajide Keshinro

    6   Johnson & Johnson, Biologics BV, Leiden, The Netherlands

Funding This study is sponsored by Johnson & Johnson. Medical writing support was provided by Aya Younes, PharmD, of Lumanity Communications Inc., and was funded by Johnson & Johnson.
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Abstract

Objective

Nipocalimab, a neonatal Fc receptor blocker, inhibits transplacental transfer of maternal immunoglobulin G (IgG) and lowers circulating maternal IgG levels. In a phase 2 study, nipocalimab demonstrated evidence of safety and efficacy in delaying or preventing fetal anemia in early-onset severe hemolytic disease of the fetus and newborn, suggesting a potential benefit in other IgG alloantibody-mediated perinatal diseases, including fetal and neonatal alloimmune thrombocytopenia (FNAIT). The phase 3 FREESIA-1 study aims to evaluate the safety and efficacy of nipocalimab in at-risk FNAIT pregnancies.

Study Design

This multicenter, placebo-controlled, double-blind, phase 3 study will enroll human platelet antigen (HPA)-1a-alloimmunized pregnant individuals with an HPA-1a-positive fetus and prior FNAIT-affected pregnancy without intracranial hemorrhage or severe bleeding in the fetus/newborn. Participants will be randomized 2:1 to weekly intravenous nipocalimab or placebo at 13 to 18 weeks of gestation until delivery. Maternal participants will receive ultrasound monitoring approximately every 2 weeks during treatment. Neonates will receive a cranial ultrasound scan, platelet count assessment, and, if needed, platelet transfusion. Maternal participants will be followed for 24 weeks and neonates/infants for 104 weeks.

Results

The primary endpoint is an adverse outcome of fetal death or adjudicated severe bleeding in utero up to 1 week postbirth, or neonatal platelet count at birth < 30 × 109/L. Key secondary endpoints include adjudicated bleeding in utero up to the first week postbirth in fetuses/neonates and platelet count at birth in neonates. Additional secondary endpoints in fetuses/neonates include death; platelet count at birth <10, <30, <50, and <150 × 109/L; nadir platelet count over the first week postbirth; platelet transfusion; adjudicated severe bleeding up to the first week postbirth; and postnatal intravenous immunoglobulin for thrombocytopenia. Other assessments include safety, patient/caregiver-reported outcomes, pharmacokinetics, pharmacodynamics, and immunogenicity of nipocalimab.

Conclusion

FREESIA-1 is the first placebo-controlled, randomized, multicenter trial designed to evaluate the safety and efficacy of nipocalimab in at-risk FNAIT pregnancies. (ClinicalTrials.gov Identifier: NCT06449651. Accessed at: https://clinicaltrials.gov/study/NCT06449651. Date of registration: June 10, 2024.)

Key Points

  • FNAIT can lead to fetal/neonatal mortality and morbidity.

  • Nipocalimab blocks IgG recycling and placental transfer.

  • Nipocalimab may reduce adverse outcomes of FNAIT.

  • FREESIA-1 will evaluate nipocalimab in FNAIT.

Keywords

FNAIT - human platelet antigen - FcRn - nipocalimab - safety - efficacy - study design


Publikationsverlauf

Eingereicht: 23. Juni 2025

Angenommen: 23. Juli 2025

Accepted Manuscript online:
28. Juli 2025

Artikel online veröffentlicht:
20. August 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

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