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.
Academic Article
Overview
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-risk 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 13-18 weeks gestational age (standard-risk) or 12 weeks 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 post-birth, 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 post-birth, neonate requiring platelet transfusion(s), adjudicated fetal and neonatal bleeding up to 1 week post-birth, 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-risk and high-risk pregnancies for FNAIT.
