{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T21:01:25Z","timestamp":1793394085982,"version":"4.5.0"},"reference-count":57,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Hematology"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Immune thrombocytopenia (ITP) is characterized by primarily autoantibody-mediated platelet destruction and impaired platelet production resulting in thrombocytopenia and an increased risk of bleeding. Other manifestations include increased risk of thrombosis and diminished quality of life. Current treatment approaches are directed toward lowering the rate of platelet destruction or stimulating platelet production to prevent bleeding. Rilzabrutinib is an oral, reversible, potent Bruton tyrosine kinase inhibitor that was specifically designed to treat immune-mediated diseases and mediates its therapeutic effect through a dual mechanism of action: (1) inhibiting B-cell activation and (2) interrupting antibody-coated cell phagocytosis by Fc gamma receptor in spleen and liver. A 24-week dose-finding phase I\/II study of rilzabrutinib in patients with ITP showed a 40% platelet response (\u2a7e2 consecutive platelet counts of \u2a7e50\u2009\u00d7\u200910\n                      <jats:sup>9<\/jats:sup>\n                      \/L and increase from baseline \u2a7e20\u2009\u00d7\u200910\n                      <jats:sup>9<\/jats:sup>\n                      \/L without rescue medication use) and a well-tolerated safety profile with only grade 1\/2 transient adverse events across dose levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>Assess the efficacy and safety of oral rilzabrutinib in adult and adolescent patients with persistent or chronic ITP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Rilzabrutinib 400\u2009mg BID is being evaluated in the ongoing LUNA 3 multicenter, double-blind, placebo-controlled phase III study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis:<\/jats:title>\n                    <jats:p>\n                      The primary endpoint is durable platelet response, defined as achieving platelet counts of \u2a7e50\u2009\u00d7\u200910\n                      <jats:sup>9<\/jats:sup>\n                      \/L for at least two-thirds of \u2a7e8 available weekly scheduled platelet measurements during the last 12\u2009weeks (including \u2a7e2 available measurements within the last 6\u2009weeks) of the 24-week blinded treatment period in the absence of rescue therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics:<\/jats:title>\n                    <jats:p>Ethical guidelines and informed consent are followed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion:<\/jats:title>\n                    <jats:p>The LUNA 3 trial will further investigate rilzabrutinib\u2019s safety and efficacy in adult and adolescent patients, with the primary goal of addressing a major objective in treating patients with ITP: durability of platelet response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trail Registration:<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT04562766: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04562766 ; EU Clinical Trials Register EudraCT 2020-002063-60: https:\/\/www.clinicaltrialsregister.eu\/ctr-search\/search?query=2020-002063-60 .<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/20406207231205431","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T05:06:34Z","timestamp":1697605594000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":39,"title":["Rilzabrutinib\n                    <i>versus<\/i>\n                    placebo in adults and adolescents with persistent or chronic immune thrombocytopenia: LUNA 3 phase III study"],"prefix":"10.1177","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2084-8810","authenticated-orcid":false,"given":"David J.","family":"Kuter","sequence":"first","affiliation":[{"name":"Hematology Division, Massachusetts General Hospital, Harvard Medical School, Bartlett Hall 150, 140 Blossom Street, Boston, MA 02114-2603, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Bussel","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waleed","family":"Ghanima","sequence":"additional","affiliation":[{"name":"\u00d8stfold Hospital Trust, Gr\u00e5lum, Norway"},{"name":"Institute of Clinical Medicine, University of Oslo, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nichola","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Immunology and Inflammation, Imperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry","family":"Gernsheimer","sequence":"additional","affiliation":[{"name":"University of Washington Medical Center and Fred Hutchinson Cancer Center, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele P.","family":"Lambert","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Philadelphia Division of Hematology and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard A.","family":"Liebman","sequence":"additional","affiliation":[{"name":"Keck School of Medicine, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Tarantino","sequence":"additional","affiliation":[{"name":"The Bleeding and Clotting Disorders Institute, University of Illinois College of Medicine Peoria, Peoria, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Lee","sequence":"additional","affiliation":[{"name":"Sanofi, Bridgewater, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailing","family":"Guo","sequence":"additional","affiliation":[{"name":"Sanofi, Bridgewater, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Daak","sequence":"additional","affiliation":[{"name":"Sanofi, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,10,18]]},"reference":[{"key":"bibr1-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2009.01247.x"},{"key":"bibr2-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2008.02911.x"},{"key":"bibr3-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.07615.x"},{"key":"bibr4-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.02147.x"},{"key":"bibr5-20406207231205431","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1002\/ajh.21616","volume":"85","author":"Terrell DR","year":"2010","journal-title":"Am J Hematol"},{"key":"bibr6-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08176.x"},{"key":"bibr7-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2019.07.015"},{"key":"bibr8-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14446"},{"key":"bibr9-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24463"},{"key":"bibr10-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-162503"},{"key":"bibr11-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp1810479"},{"key":"bibr12-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17872"},{"key":"bibr13-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000966"},{"key":"bibr14-20406207231205431","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10040789"},{"key":"bibr15-20406207231205431","doi-asserted-by":"publisher","DOI":"10.3390\/ph15070779"},{"key":"bibr16-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-312819"},{"key":"bibr17-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12869"},{"key":"bibr18-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12813"},{"key":"bibr19-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2011.01730.x"},{"key":"bibr20-20406207231205431","doi-asserted-by":"publisher","DOI":"10.2147\/PROM.S140932"},{"key":"bibr21-20406207231205431","doi-asserted-by":"publisher","DOI":"10.3390\/medicina56120667"},{"key":"bibr22-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000868"},{"key":"bibr23-20406207231205431","doi-asserted-by":"publisher","DOI":"10.3390\/jcm6020016"},{"key":"bibr24-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14977"},{"key":"bibr25-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.07995.x"},{"key":"bibr26-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0168-x"},{"key":"bibr27-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-021-00797-w"},{"key":"bibr28-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0513307"},{"key":"bibr29-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1586\/1744666X.2016.1152888"},{"key":"bibr30-20406207231205431","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01454"},{"key":"bibr31-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.248344"},{"key":"bibr32-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1817"},{"key":"bibr33-20406207231205431","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2001130"},{"key":"bibr34-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c01170"},{"key":"bibr35-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13351"},{"key":"bibr36-20406207231205431","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13051103"},{"key":"bibr37-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1182\/hematology.2020000118"},{"key":"bibr38-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13271"},{"key":"bibr39-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2110297"},{"key":"bibr40-20406207231205431","unstructured":"Study to evaluate rilzabrutinib in adults and adolescents with persistent or chronic immune thrombocytopenia (ITP) (LUNA 3) (NCT04562766), https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04562766 (Accessed 28 October 2022)."},{"key":"bibr41-20406207231205431","unstructured":"A phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study with an open-label extension to evaluate the efficacy and safety of oral rilzabrutinib (PRN1008) in adults and adolescents with persistent or chronic immune thrombocytopenia (ITP) (EudraCT Number: 2020-002063-60), https:\/\/www.clinicaltrialsregister.eu (accessed 28 October 2022)."},{"key":"bibr42-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000812"},{"key":"bibr43-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17645"},{"key":"bibr44-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021013411"},{"key":"bibr45-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2021-144504"},{"key":"bibr46-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2007.05.005"},{"key":"bibr47-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25984"},{"key":"bibr48-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06635.x"},{"key":"bibr49-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60203-2"},{"key":"bibr50-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61495-1"},{"key":"bibr51-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25125"},{"key":"bibr52-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15573"},{"key":"bibr53-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25444"},{"key":"bibr54-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2011.01587.x"},{"key":"bibr55-20406207231205431","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13385"},{"key":"bibr56-20406207231205431","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10051004"},{"key":"bibr57-20406207231205431","volume":"140","author":"Kuter DJ","year":"2022","journal-title":"Blood (ASH)"}],"container-title":["Therapeutic Advances in Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20406207231205431","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/20406207231205431","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20406207231205431","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T23:16:51Z","timestamp":1777591011000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/20406207231205431"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":57,"alternative-id":["10.1177\/20406207231205431"],"URL":"https:\/\/doi.org\/10.1177\/20406207231205431","relation":{},"ISSN":["2040-6207","2040-6215"],"issn-type":[{"value":"2040-6207","type":"print"},{"value":"2040-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1]]},"article-number":"20406207231205431"}}