Design of a Phase 3, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of Nipocalimab in Pregnancies at...

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.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.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.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.) · 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..