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CC BY 4.0 · Am J Perinatol
DOI: 10.1055/a-2753-9323
Original Article

Design of a Phase 3, Multicenter, Randomized, Open-Label Study of Nipocalimab or IVIG and Prednisone in Pregnancies at Risk for Fetal and Neonatal Alloimmune Thrombocytopenia

Authors

  • James Bussel

    1   Department of Pediatrics, Division of Hematology/Oncology, Weill Cornell Medical College, New York, New York, United States
    2   New York Presbyterian Hospital, New York, New York, United States

  • Barbara Stegmann

    3   Johnson & Johnson, Spring House, Pennsylvania, United States

  • Pamela Baker

    3   Johnson & Johnson, Spring House, Pennsylvania, United States

  • Abbie Oey

    3   Johnson & Johnson, Spring House, Pennsylvania, United States

  • Yanxin Jiang

    3   Johnson & Johnson, Spring House, Pennsylvania, United States

  • Rebecca Zaha

    3   Johnson & Johnson, Spring House, Pennsylvania, United States

  • Hillary Van Valkenburgh

    3   Johnson & Johnson, Spring House, Pennsylvania, United States

  • Babajide Keshinro

    4   Johnson & Johnson Biologics BV, Leiden, the Netherlands

Funding Information This study is sponsored by Johnson & Johnson. Medical writing support was provided by Anna Douyon, PhD, of Lumanity Communications Inc., and was funded by Johnson & Johnson. Clinical Trial Registration This study is registered with ClinicalTrials.gov (identifier: NCT06533098). Accessed November 26, 2026, at: https://clinicaltrials.gov/study/NCT06533098. Date of registration: July 30, 2024.
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Abstract

Objective

Nipocalimab, a neonatal Fc receptor blocker, showed evidence of efficacy and safety in preventing or delaying fetal anemia in a phase 2 study of early-onset severe hemolytic disease of the fetus and newborn, demonstrating potential for treatment of other maternal immunoglobulin G alloantibody-mediated fetal diseases. The phase 3 FREESIA-3 study aims to evaluate the efficacy and safety of nipocalimab or intravenous immunoglobulin (IVIG) with prednisone in pregnancies with a previous occurrence of fetal and neonatal alloimmune thrombocytopenia (FNAIT) with or without intracranial hemorrhage or severe fetal/neonatal bleeding (high- or standard-risk, respectively).

Study Design

FREESIA-3 is a phase 3, open-label, randomized, multicenter study in pregnant individuals at risk for FNAIT. Participants are randomized 4:1 to receive either weekly 45 mg/kg intravenous nipocalimab or weekly IVIG with prednisone starting at 13 to 18 weeks of gestational age (standard-risk) or 12 weeks of gestational age (high-risk) until delivery. During treatment, pregnant participants will receive ultrasound monitoring every 2 weeks for fetal bleeding, growth, and development. Postnatal follow-up is 24 weeks for maternal participants and 104 weeks for neonates/infants.

Results

The primary endpoint is an adverse outcome of death or adjudicated severe bleeding in utero up to 1 week postbirth, or platelet count at birth of < 30 × 109/L in a fetus/neonate. Secondary endpoints include fetal/neonatal death, neonatal platelet count at birth, nadir neonatal platelet count over 1 week postbirth, neonate requiring platelet transfusion(s), adjudicated fetal and neonatal bleeding up to 1 week postbirth, neonate receiving IVIG for thrombocytopenia, safety in maternal participants and neonates/infants, and immunogenicity of nipocalimab. Exploratory endpoints include patient- and caregiver-reported outcome assessments and nipocalimab pharmacokinetics and pharmacodynamics.

Conclusion

FREESIA-3, an open-label, multicenter, randomized, phase 3 study, will evaluate the efficacy and safety of nipocalimab in both standard- and high-risk pregnancies for FNAIT.

Key Points

  • FNAIT is a transplacental alloantibody-driven disease.

  • Nipocalimab blocks IgG recycling, lowering IgG levels.

  • Nipocalimab blocks IgG placental transfer to the fetus.

  • Nipocalimab reduced adverse outcomes in EOS-HDFN.

  • FREESIA-3 studies nipocalimab efficacy/safety in FNAIT.

Keywords

neonatal Fc receptor blocker - FcRn - FNAIT - safety - efficacy - study design - thrombocytopenia

Supplementary Material



Publication History

Received: 30 October 2025

Accepted: 09 November 2025

Accepted Manuscript online:
25 November 2025

Article published online:
12 December 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/)

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