PMID- 29093180
OWN - NLM
STAT- MEDLINE
DCOM- 20180723
LR  - 20181218
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Linking)
VI  - 9
IP  - 414
DP  - 2017 Nov 1
TI  - The FcRn inhibitor rozanolixizumab reduces human serum IgG concentration: A 
      randomized phase 1 study.
LID - eaan1208 [pii]
LID - 10.1126/scitranslmed.aan1208 [doi]
AB  - Pathogenic immunoglobulin G (IgG) autoantibodies characterize some human 
      autoimmune diseases; their high concentration and long half-life are dependent on 
      recycling by the neonatal Fc receptor (FcRn). Inhibition of FcRn is an attractive 
      new treatment concept for IgG-mediated autoimmune diseases. Rozanolixizumab 
      (UCB7665; CA170_01519.g57 IgG4P) is an anti-human FcRn monoclonal antibody. In 
      cynomolgus monkeys, rozanolixizumab reduced IgG (maximum 75 to 90% by about day 
      10), was well tolerated, and did not increase risk of infection. We also report a 
      first-in-human, randomized, double-blind, placebo-controlled, dose-escalating 
      study of intravenous (IV) or subcutaneous (SC) rozanolixizumab in healthy 
      subjects (NCT02220153). The primary objective was to evaluate safety and 
      tolerability. Secondary objectives were assessment of rozanolixizumab 
      pharmacokinetics and pharmacodynamics, including effects on circulating IgG 
      concentrations. Forty-nine subjects were randomized to receive rozanolixizumab (n 
      = 36) or placebo (n = 13) across six cohorts. The first three cohorts received IV 
      doses, and the subsequent three cohorts received SC doses, of rozanolixizumab 1, 
      4, or 7 mg/kg (n = 6 for each cohort; plus n = 7 or 6 for placebo, respectively). 
      The most frequent treatment-emergent adverse event [TEAE; headache, 14 of 36 
      (38.9%) subjects] was dose-dependent and more prominent after IV administration. 
      Severe TEAEs occurred in four subjects, all in the highest-dose IV group 
      [headache (n = 3) and back pain (n = 1)]. Rozanolixizumab pharmacokinetics 
      demonstrated nonlinear increases with dose. There were sustained dose-dependent 
      reductions in serum IgG concentrations (IV and SC rozanolixizumab). These data 
      provide clinical evidence for the therapeutic potential of rozanolixizumab.
CI  - Copyright (c) 2017 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works.
FAU - Kiessling, Peter
AU  - Kiessling P
AUID- ORCID: 0000-0002-5890-3646
AD  - UCB Pharma, 40789 Monheim, Germany.
FAU - Lledo-Garcia, Rocio
AU  - Lledo-Garcia R
AUID- ORCID: 0000-0002-6142-1074
AD  - UCB Pharma, Slough SL1 3WE, UK. rocio.lledo-garcia@ucb.com.
FAU - Watanabe, Shikiko
AU  - Watanabe S
AD  - UCB Pharma, Braine, 1420 Braine-l'Alleud, Belgium.
FAU - Langdon, Grant
AU  - Langdon G
AD  - PTx Solutions Ltd., London, UK.
FAU - Tran, Diep
AU  - Tran D
AD  - UCB Pharma, Slough SL1 3WE, UK.
FAU - Bari, Muhammad
AU  - Bari M
AD  - UCB Pharma, Slough SL1 3WE, UK.
FAU - Christodoulou, Louis
AU  - Christodoulou L
AD  - UCB Pharma, Slough SL1 3WE, UK.
FAU - Jones, Emma
AU  - Jones E
AD  - Veramed Ltd., Twickenham TW1 3QS, UK.
FAU - Price, Graham
AU  - Price G
AUID- ORCID: 0000-0003-4650-1241
AD  - UCB Pharma, Slough SL1 3WE, UK.
FAU - Smith, Bryan
AU  - Smith B
AD  - UCB Pharma, Slough SL1 3WE, UK.
FAU - Brennan, Frank
AU  - Brennan F
AD  - UCB Pharma, Slough SL1 3WE, UK.
FAU - White, Ian
AU  - White I
AUID- ORCID: 0000-0002-1334-262X
AD  - UCB Pharma, Slough SL1 3WE, UK.
FAU - Jolles, Stephen
AU  - Jolles S
AUID- ORCID: 0000-0002-7394-6804
AD  - Department of Immunology, University Hospital of Wales, Cardiff CF14 4XW, UK.
LA  - eng
SI  - ClinicalTrials.gov/NCT02220153
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, Fc)
RN  - P7186074QC (rozanolixizumab)
RN  - TW3XAW0RCY (Fc receptor, neonatal)
SB  - IM
EIN - Sci Transl Med. 2017 Dec 6;9(419):. PMID: 29212714
CIN - Transplantation. 2018 Mar;102(3):342-344. PMID: 29461460
MH  - Adult
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacokinetics/*pharmacology
MH  - Antibodies, Monoclonal, Humanized/pharmacokinetics/*pharmacology
MH  - Area Under Curve
MH  - Demography
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Histocompatibility Antigens Class I/metabolism
MH  - Humans
MH  - Immunoglobulin G/*blood
MH  - Macaca fascicularis
MH  - Male
MH  - Middle Aged
MH  - Receptors, Fc/*antagonists & inhibitors/metabolism
MH  - Toxicity Tests
EDAT- 2017/11/03 06:00
MHDA- 2018/07/24 06:00
CRDT- 2017/11/03 06:00
PHST- 2017/03/07 00:00 [received]
PHST- 2017/06/28 00:00 [revised]
PHST- 2017/09/27 00:00 [accepted]
PHST- 2017/11/03 06:00 [entrez]
PHST- 2017/11/03 06:00 [pubmed]
PHST- 2018/07/24 06:00 [medline]
AID - 9/414/eaan1208 [pii]
AID - 10.1126/scitranslmed.aan1208 [doi]
PST - ppublish
SO  - Sci Transl Med. 2017 Nov 1;9(414):eaan1208. doi: 10.1126/scitranslmed.aan1208.