Design of a Phase 3, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of Nipocalimab in Pregnancies at Risk for Fetal and Neonatal Alloimmune Thrombocytopenia (FREESIA-1)

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). FREESIA-1 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 13-18 weeks of gestation until delivery. Maternal participants will receive ultrasound monitoring every ~2 weeks during treatment. Neonates will receive 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 post-birth, or neonatal platelet count at birth <30×10⁹/L. Key secondary endpoints include adjudicated bleeding in utero up to the first week post-birth 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 post-birth; platelet transfusion; adjudicated severe bleeding up to the first week post-birth; and postnatal intravenous immunoglobulin for thrombocytopenia. Other assessments include safety, patient/caregiver-reported outcomes, pharmacokinetics, pharmacodynamics, and immunogenicity of nipocalimab. <b>Conclusion:</b> FREESIA-1 is the first placebo-controlled, randomized, multicenter trial designed to evaluate the safety and efficacy of nipocalimab in at-risk FNAIT pregnancies.

Publikationsverlauf

Eingereicht: 23. Juni 2025

Angenommen: 23. Juli 2025

Accepted Manuscript online:
28. Juli 2025