PMID- 35570983
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2468-0249 (Electronic)
IS  - 2468-0249 (Linking)
VI  - 7
IP  - 5
DP  - 2022 May
TI  - Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VIS649 
      (Sibeprenlimab), an APRIL-Neutralizing IgG(2) Monoclonal Antibody, in Healthy 
      Volunteers.
PG  - 993-1003
LID - 10.1016/j.ekir.2022.01.1073 [doi]
AB  - INTRODUCTION: VIS649 (sibeprenlimab), a humanized IgG(2) monoclonal antibody that 
      inhibits APRIL, is being developed as a potential treatment for IgA nephropathy 
      (IgAN). This phase 1, first-in-human, randomized, double-blind, single ascending 
      dose study aimed to evaluate the safety, pharmacokinetics (PK), and 
      pharmacodynamics (PD) of VIS649 in healthy adults. METHODS: Participants were 
      randomized to VIS649 (sequential i.v. dosing cohorts: 0.5, 2.0, 6.0, 12.0 mg/kg) 
      or placebo; a further cohort received VIS649 6.0 mg/kg or placebo followed by a 
      tetanus/diphtheria vaccine challenge. RESULTS: A total of 51 participants were 
      randomized, dosed, and analyzed for safety (7 for each VIS649 dose; 8 for 
      placebo; 10 for VIS649 + vaccine; 5 for placebo + vaccine). There were no serious 
      adverse events (AEs) or AEs leading to study discontinuation. VIS649 had 
      nonlinear PK: half-life increased with dose and drug exposure increased in a 
      greater than dose-proportional manner. Serum APRIL, IgA, galactose-deficient (Gd) 
      IgA(1), IgG, and IgM were reversibly suppressed in a dose-dependent manner, with 
      a dose-response in time to recovery. Tetanus and diphtheria serum IgG titers 
      increased after recall vaccination. CONCLUSION: VIS649 was safe, well tolerated, 
      and reversibly suppressed APRIL and various immunoglobulins, without loss of 
      antigen-specific vaccination response. Further clinical development of VIS649 for 
      IgAN is warranted. Trial registration: ClinicalTrials.gov: NCT03719443.
CI  - (c) 2022 International Society of Nephrology. Published by Elsevier Inc.
FAU - Mathur, Mohit
AU  - Mathur M
AD  - Visterra, Inc., Waltham, Massachusetts, USA.
FAU - Barratt, Jonathan
AU  - Barratt J
AD  - John Walls Renal Unit, Leicester General Hospital, Leicester, UK.
FAU - Suzuki, Yusuke
AU  - Suzuki Y
AD  - Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan.
FAU - Engler, Frank
AU  - Engler F
AD  - Certara USA, Inc., Princeton, New Jersey, USA.
FAU - Pasetti, Marcela F
AU  - Pasetti MF
AD  - Center for Vaccine Development, University of Maryland School of Medicine, 
      Baltimore, Maryland, USA.
FAU - Yarbrough, Jill
AU  - Yarbrough J
AD  - Visterra, Inc., Waltham, Massachusetts, USA.
FAU - Sloan, Susan
AU  - Sloan S
AD  - Visterra, Inc., Waltham, Massachusetts, USA.
FAU - Oldach, David
AU  - Oldach D
AD  - Visterra, Inc., Waltham, Massachusetts, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT03719443
PT  - Journal Article
DEP - 20220208
PL  - United States
TA  - Kidney Int Rep
JT  - Kidney international reports
JID - 101684752
PMC - PMC9091613
OTO - NOTNLM
OT  - APRIL
OT  - IgA nephropathy
OT  - clinical trial
OT  - galactose-deficient IgA
OT  - glomerulonephritis
OT  - monoclonal antibody
EDAT- 2022/05/17 06:00
MHDA- 2022/05/17 06:01
PMCR- 2022/02/08
CRDT- 2022/05/16 03:53
PHST- 2021/12/10 00:00 [received]
PHST- 2022/01/27 00:00 [revised]
PHST- 2022/01/31 00:00 [accepted]
PHST- 2022/05/16 03:53 [entrez]
PHST- 2022/05/17 06:00 [pubmed]
PHST- 2022/05/17 06:01 [medline]
PHST- 2022/02/08 00:00 [pmc-release]
AID - S2468-0249(22)01135-4 [pii]
AID - 10.1016/j.ekir.2022.01.1073 [doi]
PST - epublish
SO  - Kidney Int Rep. 2022 Feb 8;7(5):993-1003. doi: 10.1016/j.ekir.2022.01.1073. 
      eCollection 2022 May.