PMID- 33163724
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220418
IS  - 2468-0249 (Electronic)
IS  - 2468-0249 (Linking)
VI  - 5
IP  - 11
DP  - 2020 Nov
TI  - Safety, Tolerability and Efficacy of Narsoplimab, a Novel MASP-2 Inhibitor for 
      the Treatment of IgA Nephropathy.
PG  - 2032-2041
LID - 10.1016/j.ekir.2020.08.003 [doi]
AB  - INTRODUCTION: Narsoplimab is a human monoclonal antibody against 
      mannan-associated lectin-binding serine protease-2 (MASP-2). Now in a phase 3 
      study, narsoplimab was evaluated in a staged phase 2 study assessing safety and 
      effectiveness in high-risk patients with IgA nephropathy (IgAN). METHODS: 
      Substudy 1 was a single-arm open-label study of 12 weekly infusions and tapered 
      corticosteroids, with 6 weeks of follow-up. In substudy 2, patients were 
      randomized 1:1 to receive a course of treatment consisting of once-weekly 
      narsoplimab or vehicle infusions for 12 weeks. After 6 weeks of follow-up, both 
      substudy 2 groups could continue in an open-label extension, receiving 1 or more 
      narsoplimab courses at the investigator's discretion. RESULTS: The most commonly 
      reported adverse events (AEs) included headache, upper respiratory infection, and 
      fatigue. Most AEs were mild or moderate and transient. No treatment-related 
      serious AEs were reported. All 4 patients who were enrolled in substudy 1 had 
      reductions in 24-hour urine protein excretion (UPE) at week 18, ranging from 54% 
      to 95% compared with baseline. In substudy 2, the vehicle and narsoplimab groups 
      had similar proteinuria reductions at week 18. Eight patients (3 vehicle, 5 
      narsoplimab) continued in the dosing extension; all received narsoplimab. Median 
      reduction in 24-hour UPE in these 8 patients was 61.4% at 31 to 54 weeks 
      postbaseline. Estimated glomerular filtration rates (eGFR) remained stable in 
      both substudies. CONCLUSION: This interim analysis suggests that narsoplimab 
      treatment is safe, is well tolerated, and may result in clinically meaningful 
      reductions in proteinuria and stability of eGFR in high-risk patients with 
      advanced IgAN.
CI  - (c) 2020 Published by Elsevier, Inc., on behalf of the International Society of 
      Nephrology.
FAU - Lafayette, Richard A
AU  - Lafayette RA
AD  - Division of Nephrology, Department of Medicine, Stanford University, Stanford, 
      California, USA.
FAU - Rovin, Brad H
AU  - Rovin BH
AD  - Division of Nephrology, The Ohio State University Wexner Medical Center, 
      Columbus, Ohio, USA.
FAU - Reich, Heather N
AU  - Reich HN
AD  - Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
FAU - Tumlin, James A
AU  - Tumlin JA
AD  - NephroNet Clinical Research Consortium, Atlanta, Georgia, USA.
FAU - Floege, Jurgen
AU  - Floege J
AD  - Department of Nephrology and Clinical Immunology, RWTH Aachen University 
      Hospital, Aachen, Germany.
FAU - Barratt, Jonathan
AU  - Barratt J
AD  - Department of Infection, Immunity and Inflammation, University of Leicester, 
      Leicester, UK.
LA  - eng
PT  - Journal Article
DEP - 20200813
PL  - United States
TA  - Kidney Int Rep
JT  - Kidney international reports
JID - 101684752
PMC - PMC7609886
OTO - NOTNLM
OT  - IgA nephropathy
OT  - MASP-2
OT  - complement system
OT  - lectin pathway
OT  - mannan-associated lectin-binding serine protease-2
OT  - narsoplimab
EDAT- 2020/11/10 06:00
MHDA- 2020/11/10 06:01
PMCR- 2020/08/13
CRDT- 2020/11/09 05:34
PHST- 2020/05/27 00:00 [received]
PHST- 2020/07/11 00:00 [revised]
PHST- 2020/08/04 00:00 [accepted]
PHST- 2020/11/09 05:34 [entrez]
PHST- 2020/11/10 06:00 [pubmed]
PHST- 2020/11/10 06:01 [medline]
PHST- 2020/08/13 00:00 [pmc-release]
AID - S2468-0249(20)31441-8 [pii]
AID - 10.1016/j.ekir.2020.08.003 [doi]
PST - epublish
SO  - Kidney Int Rep. 2020 Aug 13;5(11):2032-2041. doi: 10.1016/j.ekir.2020.08.003. 
      eCollection 2020 Nov.