{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:14:30Z","timestamp":1787004870286,"version":"build-2736575974"},"reference-count":48,"publisher":"Georg Thieme Verlag KG","issue":"10","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"This study is sponsored by Johnson & Johnson"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Perinatol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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).<\/jats:p>\n                  <jats:p>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\u2009mg\/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.<\/jats:p>\n                  <jats:p>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\u2009&lt;\u200930\u2009\u00d7\u2009109\/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.<\/jats:p>\n                  <jats:p>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.<\/jats:p>","DOI":"10.1055\/a-2753-9323","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:27:04Z","timestamp":1764116824000},"page":"1335-1344","source":"Crossref","is-referenced-by-count":5,"title":["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"],"prefix":"10.1055","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct06533098","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"James","family":"Bussel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Hematology\/Oncology, Weill Cornell Medical College, New York, New York, United States"},{"name":"New York Presbyterian Hospital, New York, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Stegmann","sequence":"additional","affiliation":[{"name":"Johnson & Johnson, Spring House, Pennsylvania, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Baker","sequence":"additional","affiliation":[{"name":"Johnson & Johnson, Spring House, Pennsylvania, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbie","family":"Oey","sequence":"additional","affiliation":[{"name":"Johnson & Johnson, Spring House, Pennsylvania, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Johnson & Johnson, Spring House, Pennsylvania, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Zaha","sequence":"additional","affiliation":[{"name":"Johnson & Johnson, Spring House, Pennsylvania, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hillary","family":"Van Valkenburgh","sequence":"additional","affiliation":[{"name":"Johnson & Johnson, Spring House, Pennsylvania, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babajide","family":"Keshinro","sequence":"additional","affiliation":[{"name":"Johnson & Johnson Biologics BV, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"issue":"01","key":"ref1","doi-asserted-by":"crossref","first-page":"102704","DOI":"10.1016\/j.transci.2019.102704","article-title":"Epidemiology and management of fetal and neonatal alloimmune thrombocytopenia","volume":"59","author":"T W de Vos","year":"2020","journal-title":"Transfus Apher Sci"},{"issue":"11","key":"ref2","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1182\/blood-2016-10-739656","article-title":"Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review","volume":"129","author":"D Winkelhorst","year":"2017","journal-title":"Blood"},{"issue":"04","key":"ref3","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1111\/bjh.17731","article-title":"Clinical characteristics of human platelet antigen (HPA)-1a and HPA-5b alloimmunised pregnancies and the association between platelet HPA-5b antibodies and symptomatic fetal neonatal alloimmune thrombocytopenia","volume":"195","author":"T W de Vos","year":"2021","journal-title":"Br J Haematol"},{"issue":"05","key":"ref4","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/j.1600-0897.1996.tb00172.x","article-title":"Evolution of maternofetal transport of immunoglobulins during human pregnancy","volume":"36","author":"A Malek","year":"1996","journal-title":"Am J Reprod Immunol"},{"issue":"04","key":"ref5","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1111\/trf.15152","article-title":"Risk of HPA-1a-immunization in HPA-1a-negative women after giving birth to an HPA-1a-positive child","volume":"59","author":"J Kjeldsen-Kragh","year":"2019","journal-title":"Transfusion"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"223","DOI":"10.2147\/IJWH.S90753","article-title":"Current perspectives on fetal and neonatal alloimmune thrombocytopenia - increasing clinical concerns and new treatment opportunities","volume":"9","author":"H Tiller","year":"2017","journal-title":"Int J Womens Health"},{"issue":"10","key":"ref7","doi-asserted-by":"crossref","first-page":"e173","DOI":"10.1111\/1471-0528.15642","article-title":"Prenatal management of pregnancies at risk of fetal neonatal alloimmune thrombocytopenia (FNAIT): scientific impact paper no. 61","volume":"126","author":"F Regan","year":"2019","journal-title":"BJOG"},{"issue":"11","key":"ref8","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1111\/j.1471-0528.2010.02657.x","article-title":"Screening in pregnancy for fetal or neonatal alloimmune thrombocytopenia: systematic review","volume":"117","author":"M M Kamphuis","year":"2010","journal-title":"BJOG"},{"issue":"04","key":"ref9","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1136\/jcp.55.4.289","article-title":"Neonatal alloimmune thrombocytopenia in the Irish population: a discrepancy between observed and expected cases","volume":"55","author":"A Davoren","year":"2002","journal-title":"J Clin Pathol"},{"issue":"04","key":"ref10","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1542\/peds.2013-3320","article-title":"Incidence and consequences of neonatal alloimmune thrombocytopenia: a systematic review","volume":"133","author":"M M Kamphuis","year":"2014","journal-title":"Pediatrics"},{"issue":"01","key":"ref11","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/trf.13274","article-title":"Fetal and neonatal alloimmune thrombocytopenia: predictive factors of intracranial hemorrhage","volume":"56","author":"F Delbos","year":"2016","journal-title":"Transfusion"},{"issue":"04","key":"ref12","doi-asserted-by":"crossref","first-page":"e304","DOI":"10.1016\/S2352-3026(25)00029-8","article-title":"Rising to the challenge: an international Delphi consensus study on fetal and neonatal alloimmune thrombocytopenia","volume":"12","author":"R Pothof","year":"2025","journal-title":"Lancet Haematol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"113385","DOI":"10.1016\/j.jpeds.2023.02.031","article-title":"Children newly diagnosed with fetal and neonatal alloimmune thrombocytopenia: neurodevelopmental outcome at school age","volume":"258","author":"T W de Vos","year":"2023","journal-title":"J Pediatr"},{"issue":"06","key":"ref14","doi-asserted-by":"crossref","first-page":"656.e1","DOI":"10.1016\/j.ajog.2025.06.052","article-title":"Increased frequency of autism by previous diagnosis and screening in children with fetal-neonatal alloimmune thrombocytopenia with and without an intracranial hemorrhage","volume":"233","author":"E A McFarland","year":"2025","journal-title":"Am J Obstet Gynecol"},{"issue":"01","key":"ref15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1056\/NEJM199707033370104","article-title":"Fetal alloimmune thrombocytopenia","volume":"337","author":"J B Bussel","year":"1997","journal-title":"N Engl J Med"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.3389\/fimmu.2018.01308","article-title":"What is the burden of immunoglobulin replacement therapy in adult patients with primary immunodeficiencies? A systematic review","volume":"9","author":"G L Jones","year":"2018","journal-title":"Front Immunol"},{"key":"ref17","first-page":"S105","article-title":"Managing cost of care and healthcare utilization in patients using immunoglobulin agents","volume":"25","author":"L J Vaughan","year":"2019","journal-title":"Am J Manag Care"},{"issue":"17","key":"ref18","doi-asserted-by":"crossref","first-page":"5492","DOI":"10.3390\/jcm12175492","article-title":"Pregnant women at low risk of having a child with fetal and neonatal alloimmune thrombocytopenia do not require treatment with intravenous immunoglobulin","volume":"12","author":"J Kjeldsen-Kragh","year":"2023","journal-title":"J Clin Med"},{"issue":"03","key":"ref19","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/bjh.15813","article-title":"Fetal and neonatal alloimmune thrombocytopenia: recommendations for evidence-based practice, an international approach","volume":"185","author":"L Lieberman","year":"2019","journal-title":"Br J Haematol"},{"issue":"04","key":"ref20","doi-asserted-by":"crossref","first-page":"471.e1","DOI":"10.1016\/j.ajog.2016.04.033","article-title":"Omission of fetal sampling in treatment of subsequent pregnancies in fetal-neonatal alloimmune thrombocytopenia","volume":"215","author":"M Lakkaraja","year":"2016","journal-title":"Am J Obstet Gynecol"},{"issue":"01","key":"ref21","doi-asserted-by":"crossref","first-page":"102711","DOI":"10.1016\/j.transci.2019.102711","article-title":"Fetal and neonatal alloimmune thrombocytopenia - the Norwegian management model","volume":"59","author":"H Tiller","year":"2020","journal-title":"Transfus Apher Sci"},{"issue":"08","key":"ref22","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1080\/17474086.2017.1346471","article-title":"Fetal and neonatal alloimmune thrombocytopenia: evidence based antenatal and postnatal management strategies","volume":"10","author":"D Winkelhorst","year":"2017","journal-title":"Expert Rev Hematol"},{"issue":"05","key":"ref23","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1016\/S0002-9378(96)70582-3","article-title":"Antenatal management of alloimmune thrombocytopenia with intravenous gamma-globulin: a randomized trial of the addition of low-dose steroid to intravenous gamma-globulin","volume":"174","author":"J B Bussel","year":"1996","journal-title":"Am J Obstet Gynecol"},{"issue":"01","key":"ref24","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1097\/01.AOG.0000192404.25780.68","article-title":"Parallel randomized trials of risk-based therapy for fetal alloimmune thrombocytopenia","volume":"107","author":"R L Berkowitz","year":"2006","journal-title":"Obstet Gynecol"},{"issue":"01","key":"ref25","doi-asserted-by":"crossref","first-page":"102710","DOI":"10.1016\/j.transci.2019.102710","article-title":"The use of IVIg in fetal and neonatal alloimmune thrombocytopenia-principles and mechanisms","volume":"59","author":"H Wabnitz","year":"2020","journal-title":"Transfus Apher Sci"},{"issue":"03","key":"ref26","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.jaci.2020.07.016","article-title":"Targeting FcRn for immunomodulation: benefits, risks, and practical considerations","volume":"146","author":"H H Peter","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.addr.2015.02.005","article-title":"The neonatal Fc receptor, FcRn, as a target for drug delivery and therapy","volume":"91","author":"J T Sockolosky","year":"2015","journal-title":"Adv Drug Deliv Rev"},{"issue":"15","key":"ref28","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1007\/s00018-010-0318-6","article-title":"The neonatal Fc receptor as therapeutic target in IgG-mediated autoimmune diseases","volume":"67","author":"A Sesarman","year":"2010","journal-title":"Cell Mol Life Sci"},{"issue":"06","key":"ref29","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1084\/jem.180.6.2377","article-title":"A major histocompatibility complex class I-like Fc receptor cloned from human placenta: possible role in transfer of immunoglobulin G from mother to fetus","volume":"180","author":"C M Story","year":"1994","journal-title":"J Exp Med"},{"issue":"06","key":"ref30","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1056\/NEJMoa2314466","article-title":"Nipocalimab in early-onset severe hemolytic disease of the fetus and newborn","volume":"391","author":"K J Moise Jr","year":"2024","journal-title":"N Engl J Med"},{"issue":"04","key":"ref31","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1002\/cpt.1276","article-title":"M281, an anti-FcRn antibody: pharmacodynamics, pharmacokinetics, and safety across the full range of IgG reduction in a first-in-human study","volume":"105","author":"L E Ling","year":"2019","journal-title":"Clin Pharmacol Ther"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1055\/a-2666-5642","article-title":"Design of a Phase 3, multicenter, randomized, placebo-controlled, double-blind study of nipocalimab in pregnancies at risk for fetal and neonatal alloimmune thrombocytopenia","author":"H Tiller","year":"2025","journal-title":"Am J Perinatol"},{"issue":"02","key":"ref34","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.ajog.2021.04.211","article-title":"New developments in fetal and neonatal alloimmune thrombocytopenia","volume":"225","author":"J B Bussel","year":"2021","journal-title":"Am J Obstet Gynecol"},{"key":"ref35","first-page":"139","volume-title":"Bayley Scales of Infant Development","author":"E M Lennon","year":"2020","edition":"2nd ed:"},{"key":"ref36","volume-title":"User's Manual for the SF36v2 Health Survey","author":"M E Maruish","year":"2011","edition":"3rd ed."},{"issue":"10","key":"ref37","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1007\/s11136-011-9903-x","article-title":"Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L)","volume":"20","author":"M Herdman","year":"2011","journal-title":"Qual Life Res"},{"issue":"07","key":"ref38","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1007\/s11136-012-0322-4","article-title":"Measurement properties of the EQ-5D-5L compared to the EQ-5D-3L across eight patient groups: a multi-country study","volume":"22","author":"M F Janssen","year":"2013","journal-title":"Qual Life Res"},{"issue":"08","key":"ref39","doi-asserted-by":"crossref","first-page":"e0203276","DOI":"10.1371\/journal.pone.0203276","article-title":"A descriptive system for the Infant health-related Quality of life Instrument (IQI): measuring health with a mobile app","volume":"13","author":"R Jabrayilov","year":"2018","journal-title":"PLoS One"},{"issue":"04","key":"ref40","doi-asserted-by":"crossref","first-page":"e0230852","DOI":"10.1371\/journal.pone.0230852","article-title":"A two-step procedure to generate utilities for the Infant health-related Quality of life Instrument (IQI)","volume":"15","author":"P FM Krabbe","year":"2020","journal-title":"PLoS One"},{"issue":"04","key":"ref41","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/j.ajog.2006.06.066","article-title":"Antenatal noninvasive treatment of patients at risk for alloimmune thrombocytopenia without a history of intracranial hemorrhage","volume":"195","author":"Y Yinon","year":"2006","journal-title":"Am J Obstet Gynecol"},{"issue":"02","key":"ref42","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1159\/000380907","article-title":"Low-dose versus standard-dose intravenous immunoglobulin to prevent fetal intracranial hemorrhage in fetal and neonatal alloimmune thrombocytopenia: a randomized trial","volume":"38","author":"N P Paridaans","year":"2015","journal-title":"Fetal Diagn Ther"},{"issue":"09","key":"ref43","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.1111\/trf.13712","article-title":"Lower-dose intravenous immunoglobulins for the treatment of fetal and neonatal alloimmune thrombocytopenia: a cohort study","volume":"56","author":"M Kamphuis","year":"2016","journal-title":"Transfusion"},{"issue":"04","key":"ref44","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.ajog.2006.05.001","article-title":"Alloimmune thrombocytopenia: state of the art 2006","volume":"195","author":"R L Berkowitz","year":"2006","journal-title":"Am J Obstet Gynecol"},{"issue":"02","key":"ref46","doi-asserted-by":"crossref","first-page":"e004278","DOI":"10.1136\/rmdopen-2024-004278","article-title":"Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study","volume":"10","author":"P C Taylor","year":"2024","journal-title":"RMD Open"},{"issue":"08","key":"ref47","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s40261-024-01380-0","article-title":"Pharmacokinetics and pharmacodynamics of nipocalimab, a neonatal Fc receptor blocker, in healthy Japanese volunteers","volume":"44","author":"N Matsushima","year":"2024","journal-title":"Clin Drug Investig"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1302714","DOI":"10.3389\/fnins.2024.1302714","article-title":"Pharmacokinetics and pharmacodynamics across infusion rates of intravenously administered nipocalimab: results of a phase 1, placebo-controlled study","volume":"18","author":"J H Leu","year":"2024","journal-title":"Front Neurosci"},{"issue":"02","key":"ref49","doi-asserted-by":"crossref","first-page":"e207937","DOI":"10.1212\/WNL.0000000000207937","article-title":"Safety and efficacy of nipocalimab in patients with generalized myasthenia gravis: results from the randomized phase 2 Vivacity-MG study","volume":"102","author":"C Antozzi","year":"2024","journal-title":"Neurology"},{"issue":"06","key":"ref50","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1097\/AOG.0b013e3181c2bde8","article-title":"Pregnancy and laboratory studies: a reference table for clinicians","volume":"114","author":"M Abbassi-Ghanavati","year":"2009","journal-title":"Obstet Gynecol"}],"container-title":["American Journal of Perinatology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2753-9323.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:48:01Z","timestamp":1783550881000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2753-9323"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,25]]},"references-count":48,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,7,8]]},"published-print":{"date-parts":[[2026,7]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2753-9323","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0735-1631","1098-8785"],"issn-type":[{"value":"0735-1631","type":"print"},{"value":"1098-8785","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,11,25]]},"published":{"date-parts":[[2025,11,25]]}}}