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![]() ROBAK, Tadeusz, KAZMIERCZAK, Maciej, JARQUE, Isidro, MUSTEAŢĂ, Vasile, TRELINSKI, Jacek, COOPER, Nichola, KIESSLING, Peter C., MASSOW, Ute, WOLTERING, Franz, SNIPES, Rose G., KE, Juan, LANGDON, Grant, BUSSEL, James Bruce, JOLLES, Stephen. Phase 2 multiple-dose study of an FcRn inhibitor, rozanolixizumab, in patients with primary immune thrombocytopenia. In: Blood Advances, 2020, nr. 4(17), pp. 4136-4146. ISSN 2473-9537. DOI: https://doi.org/10.1182/bloodadvances.2020002003 |
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Blood Advances | |
Numărul 4(17) / 2020 / ISSN 2473-9537 | |
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DOI:https://doi.org/10.1182/bloodadvances.2020002003 | |
Pag. 4136-4146 | |
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Primary immune thrombocytopenia (ITP) is a predominantly immunoglobulin G (IgG)-autoantibody-mediated disease characterized by isolated thrombocytopenia. Rozanolixizumab, a subcutaneously infused humanized monoclonal anti-neonatal Fc receptor (FcRn) antibody, reduced serum IgG in healthy volunteers. In this phase 2, multicenter, open-label study, patients with persistent/chronic primary ITP received 1 to 5 once-weekly subcutaneous infusions of rozanolixizumab (cumulative doses, 15-21 mg/kg). Primary objectives were safety and tolerability, and secondary objectives were clinical efficacy (change in platelet count) and pharmacodynamic effect (change in IgG). In all, 51 (77.3%) of 66 patients reported 1 or more adverse events (AEs), all mild-to-moderate, most commonly headaches (26 [39.4%] of 66), of which 15 were treatment related. Four patients had serious AEs, but none were treatment related. No AEs resulted in discontinuation of the study drug. No serious infections occurred. Platelet counts of $50 3 109/L were achieved at least once at any time after multiple infusions (5 3 4, 3 3 7, or 2 3 10 mg/kg: 35.7%, 35.7%, and 45.5% of patients, respectively) or single infusions (15 or 20 mg/kg: 66.7% and 54.5% patients, respectively). Minimum mean IgG levels and maximum mean platelet counts both occurred by day 8 in the higher (15 and 20 mg/kg) single-dose cohorts and maximum platelet count occurred by day 11 onward in the multiple-dose cohorts. No clinically meaningful changes occurred in IgA, IgM, IgE, or albumin levels. In patients with persistent/chronic primary ITP, rozanolixizumab demonstrated a favorable safety profile and rapid, substantial platelet increases concordant with substantial IgG reductions, especially with single doses. By day 8, in the 15 and 20 mg/kg single-dose cohorts, .50% patients achieved clinically relevant platelet responses ($50 3 109/L), coinciding with the lowest mean IgG levels. These data support phase 3 development of rozanolixizumab in persistent/chronic primary ITP. |
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Cuvinte-cheie Idiopathic Thrombocytopenic Purpura, Romiplostim, Eltrombopag |
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DataCite XML Export
<?xml version='1.0' encoding='utf-8'?> <resource xmlns:xsi='http://www.w3.org/2001/XMLSchema-instance' xmlns='http://datacite.org/schema/kernel-3' xsi:schemaLocation='http://datacite.org/schema/kernel-3 http://schema.datacite.org/meta/kernel-3/metadata.xsd'> <identifier identifierType='DOI'>10.1182/bloodadvances.2020002003</identifier> <creators> <creator> <creatorName>Robak, T.</creatorName> <affiliation>Medical University of Lodz, Polonia</affiliation> </creator> <creator> <creatorName>Kazmierczak, M.</creatorName> <affiliation>Poznan University of Medical Sciences, Polonia</affiliation> </creator> <creator> <creatorName>Jarque, I.</creatorName> <affiliation>La Fe University and Polytechnic Hospital, Valencia, Spania</affiliation> </creator> <creator> <creatorName>Musteaţă, V.G.</creatorName> <affiliation>IMSP Institutul Oncologic, Moldova, Republica</affiliation> </creator> <creator> <creatorName>Trelinski, J.</creatorName> <affiliation>Medical University of Lodz, Polonia</affiliation> </creator> <creator> <creatorName>Cooper, N.</creatorName> <affiliation> Imperial College Healthcare National Health Service Trust, London, Marea Britanie</affiliation> </creator> <creator> <creatorName>Kiessling, P.</creatorName> <affiliation>Union Chimique Belge (UCB) Pharma, Monheim-am-Rhein, Germania</affiliation> </creator> <creator> <creatorName>Massow, U.</creatorName> <affiliation>Union Chimique Belge (UCB) Pharma, Monheim-am-Rhein, Germania</affiliation> </creator> <creator> <creatorName>Woltering, F.</creatorName> <affiliation>Union Chimique Belge (UCB) Pharma, Monheim-am-Rhein, Germania</affiliation> </creator> <creator> <creatorName>Snipes, R.</creatorName> <affiliation>UCB Pharma, Raleigh, Statele Unite ale Americii</affiliation> </creator> <creator> <creatorName>Ke, J.</creatorName> <affiliation>UCB Pharma, Slough, Marea Britanie</affiliation> </creator> <creator> <creatorName>Langdon, G.</creatorName> <affiliation>PTx Solutions Ltd., London, Marea Britanie</affiliation> </creator> <creator> <creatorName>Bussel, J.</creatorName> <affiliation>Weill Cornell Medicine, New York, Statele Unite ale Americii</affiliation> </creator> <creator> <creatorName>Jolles, S.</creatorName> <affiliation> University Hospital of Wales, Cardiff, Marea Britanie</affiliation> </creator> </creators> <titles> <title xml:lang='en'>Phase 2 multiple-dose study of an FcRn inhibitor, rozanolixizumab, in patients with primary immune thrombocytopenia</title> </titles> <publisher>Instrumentul Bibliometric National</publisher> <publicationYear>2020</publicationYear> <relatedIdentifier relatedIdentifierType='ISSN' relationType='IsPartOf'>2473-9537</relatedIdentifier> <subjects> <subject>Idiopathic Thrombocytopenic Purpura</subject> <subject>Romiplostim</subject> <subject>Eltrombopag</subject> </subjects> <dates> <date dateType='Issued'>2020-09-08</date> </dates> <resourceType resourceTypeGeneral='Text'>Journal article</resourceType> <descriptions> <description xml:lang='en' descriptionType='Abstract'><p>Primary immune thrombocytopenia (ITP) is a predominantly immunoglobulin G (IgG)-autoantibody-mediated disease characterized by isolated thrombocytopenia. Rozanolixizumab, a subcutaneously infused humanized monoclonal anti-neonatal Fc receptor (FcRn) antibody, reduced serum IgG in healthy volunteers. In this phase 2, multicenter, open-label study, patients with persistent/chronic primary ITP received 1 to 5 once-weekly subcutaneous infusions of rozanolixizumab (cumulative doses, 15-21 mg/kg). Primary objectives were safety and tolerability, and secondary objectives were clinical efficacy (change in platelet count) and pharmacodynamic effect (change in IgG). In all, 51 (77.3%) of 66 patients reported 1 or more adverse events (AEs), all mild-to-moderate, most commonly headaches (26 [39.4%] of 66), of which 15 were treatment related. Four patients had serious AEs, but none were treatment related. No AEs resulted in discontinuation of the study drug. No serious infections occurred. Platelet counts of $50 3 10<sup>9</sup>/L were achieved at least once at any time after multiple infusions (5 3 4, 3 3 7, or 2 3 10 mg/kg: 35.7%, 35.7%, and 45.5% of patients, respectively) or single infusions (15 or 20 mg/kg: 66.7% and 54.5% patients, respectively). Minimum mean IgG levels and maximum mean platelet counts both occurred by day 8 in the higher (15 and 20 mg/kg) single-dose cohorts and maximum platelet count occurred by day 11 onward in the multiple-dose cohorts. No clinically meaningful changes occurred in IgA, IgM, IgE, or albumin levels. In patients with persistent/chronic primary ITP, rozanolixizumab demonstrated a favorable safety profile and rapid, substantial platelet increases concordant with substantial IgG reductions, especially with single doses. By day 8, in the 15 and 20 mg/kg single-dose cohorts, .50% patients achieved clinically relevant platelet responses ($50 3 10<sup>9</sup>/L), coinciding with the lowest mean IgG levels. These data support phase 3 development of rozanolixizumab in persistent/chronic primary ITP. </p></description> </descriptions> <formats> <format>application/pdf</format> </formats> </resource>