PMID- 32886753 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20221104 IS - 2473-9537 (Electronic) IS - 2473-9529 (Print) IS - 2473-9529 (Linking) VI - 4 IP - 17 DP - 2020 Sep 8 TI - Phase 2 multiple-dose study of an FcRn inhibitor, rozanolixizumab, in patients with primary immune thrombocytopenia. PG - 4136-4146 LID - 10.1182/bloodadvances.2020002003 [doi] AB - 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 x 109/L were achieved at least once at any time after multiple infusions (5 x 4, 3 x 7, or 2 x 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 x 109/L), coinciding with the lowest mean IgG levels. These data support phase 3 development of rozanolixizumab in persistent/chronic primary ITP. This trial was registered at www.clinicaltrials.gov as #NCT02718716. CI - (c) 2020 by The American Society of Hematology. FAU - Robak, Tadeusz AU - Robak T AD - Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland. FAU - Kazmierczak, Maciej AU - Kazmierczak M AD - Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznan, Poland. FAU - Jarque, Isidro AU - Jarque I AD - Department of Hematology, Hospital Universitario y Politecnico La Fe, Valencia, Spain. AD - Centro de Investigacion Biomedica en Red de Cancer, Instituto de Salud Carlos III, Madrid, Spain. FAU - Musteata, Vasile AU - Musteata V AD - Division of Hematology, Arensia Exploratory Medicine, Institute of Oncology, Chisinau, Moldova. FAU - Trelinski, Jacek AU - Trelinski J AD - Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland. FAU - Cooper, Nichola AU - Cooper N AD - Department of Immunology and Inflammation, Imperial College Healthcare National Health Service Trust, London, United Kingdom. FAU - Kiessling, Peter AU - Kiessling P AD - Union Chimique Belge (UCB) Pharma, Monheim-am-Rhein, Germany. FAU - Massow, Ute AU - Massow U AD - Union Chimique Belge (UCB) Pharma, Monheim-am-Rhein, Germany. FAU - Woltering, Franz AU - Woltering F AD - Union Chimique Belge (UCB) Pharma, Monheim-am-Rhein, Germany. FAU - Snipes, Rose AU - Snipes R AD - UCB Pharma, Raleigh, NC. FAU - Ke, Juan AU - Ke J AD - UCB Pharma, Slough, United Kingdom. FAU - Langdon, Grant AU - Langdon G AD - PTx Solutions Ltd, London, United Kingdom. FAU - Bussel, James B AU - Bussel JB AD - Department of Pediatrics, Weill Cornell Medicine, New York, NY; and. FAU - Jolles, Stephen AU - Jolles S AD - Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, United Kingdom. LA - eng SI - ClinicalTrials.gov/NCT02718716 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood Adv JT - Blood advances JID - 101698425 RN - 0 (Antibodies, Monoclonal, Humanized) RN - P7186074QC (rozanolixizumab) SB - IM MH - Antibodies, Monoclonal, Humanized MH - Humans MH - Platelet Count MH - *Purpura, Thrombocytopenic, Idiopathic/drug therapy MH - *Thrombocytopenia PMC - PMC7479959 COIS- Conflict-of-interest disclosure: T.R. has received consultancy fees and/or research funding from AbbVie, Acerta, Amgen, BeiGene, Gilead, Janssen, Morphosys AG, Roche, and Takeda and honoraria, research funding, or for other activities from AbbVie, Janssen, and UCB Pharma. I.J. has received consultancy fees and/or has supported speaker's bureaus for AbbVie, Alexion, Amgen, Bristol-Myers Squibb, Celgene, CellTrion, Grifols, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Servier, Shionogi, Shire, and Takeda. V.M. is an employee of the Institute of Oncology and Arensia Exploratory Medicine. N.C. has received consultancy fees, advisory board funding, and/or honoraria from Amgen, Novartis, Principia, and Rigel. G.L. has received consultancy fees from AstraZeneca, Conatus, Creablis, Medicines for Malaria Venture, Mylan, Pfizer, Sigmoid Pharma, UCB Pharma, and Ziarco. J.B.B. has received consultancy fees from Amgen, Argenx, UCB Pharma, Dova, Kezar, Momenta, Novartis, Regeneron, and Rigel and has supported speaker's bureaus for Novartis and 3SBio. S.J. has received support for studies and consultancy and speaker's bureau fees and has undertaken clinical trials and provided conference support for Binding Site, Biocryst, Biotest, CSL Behring, LFB, Grifols, Octapharma, Pharming, Shire/Takeda, SOBI, UCB Pharma, Weatherden, and Zarodex. P.K., U.M., F.W., R.S., and J.K. are employees of UCB Pharma and may hold stock or stock options. The remaining authors declare no competing financial interests. EDAT- 2020/09/05 06:00 MHDA- 2021/05/15 06:00 PMCR- 2020/09/04 CRDT- 2020/09/04 17:10 PHST- 2020/04/06 00:00 [received] PHST- 2020/07/15 00:00 [accepted] PHST- 2020/09/04 17:10 [entrez] PHST- 2020/09/05 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] PHST- 2020/09/04 00:00 [pmc-release] AID - S2473-9529(20)31176-9 [pii] AID - 2020/ADV2020002003 [pii] AID - 10.1182/bloodadvances.2020002003 [doi] PST - ppublish SO - Blood Adv. 2020 Sep 8;4(17):4136-4146. doi: 10.1182/bloodadvances.2020002003.