{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:35:53Z","timestamp":1792553753443,"version":"4.5.0"},"reference-count":44,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"unspecified","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016471","name":"Agios Pharmaceuticals","doi-asserted-by":"publisher","award":["IST-2022-000039"],"award-info":[{"award-number":["IST-2022-000039"]}],"id":[{"id":"10.13039\/100016471","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,7,12]]},"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Membranopathies encompass haemolytic disorders arising from genetic variants in erythrocyte membrane proteins, including hereditary spherocytosis and stomatocytosis. Congenital dyserythropoietic anaemia type II (CDA II) is associated with the<jats:italic>SEC23B<\/jats:italic>gene and can exhibit phenotypic similarities to membranopathies. Current treatment options for these conditions, apart from splenectomy, are primarily supportive. Mitapivat, a novel pyruvate kinase (PK) activator, has demonstrated efficacy in increasing haemoglobin levels and reducing haemolysis in patients with PK deficiency, thalassemia, sickle cell disease and a mouse model of hereditary spherocytosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and analyses<\/jats:title><jats:p><jats:bold>Sa<\/jats:bold>fe<jats:bold>t<\/jats:bold>y and eff<jats:bold>i<\/jats:bold>cacy of mitapivat<jats:bold>s<\/jats:bold>ul<jats:bold>f<\/jats:bold>ate in adult patients with er<jats:bold>y<\/jats:bold>throcyte membranopathies (SATISFY) is a prospective, multicentre, single-arm phase two trial involving approximately 25 adult patients (\u226518 years) diagnosed with a membranopathy or CDA II. During the 8-week dose escalation period, subjects will receive an initial dose of 50 mg mitapivat two times per day and may increase to 100 mg two times per day at week 4 based on the safety and changes in haemoglobin levels. Patients tolerating mitapivat well may be eligible to continue in two consecutive 24-week fixed dose periods.<\/jats:p><jats:p>The primary objective of this study is to evaluate the safety of mitapivat, assessed through the occurrence of treatment-emergent adverse events. Secondary objectives include assessing the effects of mitapivat on haemoglobin levels, haemolysis, erythropoiesis, patient-reported outcome measures and spleen size.<\/jats:p><jats:p>SATISFY aims to assess the safety and efficacy of mitapivat in adult patients with red blood cell membranopathies and CDA II, with the aim of establishing proof-of-concept in patients living with these rare conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Ethics and dissemination<\/jats:title><jats:p>NCT05935202\/CTIS:2023-503271-24-01. Findings will be published in peer-reviewed journals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration number<\/jats:title><jats:p>Clinicaltrials.gov,<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05935202\">NCT05935202<\/jats:ext-link>. CTIS:2023-503271-24-01. Registered 07-July-2023. Protocol number: 2.1.<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT05935202\">https:\/\/clinicaltrials.gov\/study\/NCT05935202<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2023-083691","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T02:59:07Z","timestamp":1722394747000},"page":"e083691","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Designing a single-arm phase 2 clinical trial of mitapivat for adult patients with erythrocyte membranopathies (SATISFY): a framework for interventional trials in rare anaemias \u2013 pilot study 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