PMID- 36434739
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221213
IS  - 2045-7022 (Print)
IS  - 2045-7022 (Electronic)
IS  - 2045-7022 (Linking)
VI  - 12
IP  - 11
DP  - 2022 Nov
TI  - Pharmacokinetic equivalence of CT-P39 and reference omalizumab in healthy 
      individuals: A randomised, double-blind, parallel-group, Phase 1 trial.
PG  - e12204
LID - 10.1002/clt2.12204 [doi]
LID - e12204
AB  - BACKGROUND: CT-P39 is being developed as a biosimilar of reference omalizumab. 
      This study aimed to assess the pharmacokinetic equivalence of CT-P39 to European 
      Union-approved and United States-licensed reference omalizumab (EU- and 
      US-omalizumab, respectively). METHODS: This two-part, randomised, parallel-group, 
      double-blind Phase 1 trial (NCT04018313) was conducted in healthy individuals 
      with a total immunoglobulin E (IgE) level </=100  international units (IU)/ml at 
      screening. In part 2, described herein, participants were randomised (1:1:1) to 
      receive a single 150 mg subcutaneous dose of CT-P39, EU-omalizumab, or 
      US-omalizumab. The primary endpoint was pharmacokinetic equivalence in terms of 
      area under the concentration-time curve (AUC) from time zero to the last 
      quantifiable concentration (AUC(0-last) ), AUC from time zero to infinity 
      (AUC(0-inf) ), and maximum serum concentration (C(max) ). Equivalence was 
      concluded if 90% confidence intervals (CIs) of the geometric least-squares means 
      ratios were contained within the predefined 80%-125% equivalence margin. 
      Additional pharmacokinetic parameters, pharmacodynamics, safety, and 
      immunogenicity were also evaluated. RESULTS: Overall, 146 participants were 
      randomised (CT-P39, N = 47; EU-omalizumab, N = 49; US-omalizumab, N = 50). For 
      all primary pharmacokinetic parameters, 90% CIs for pairwise treatment 
      comparisons were within the 80%-125% equivalence margin, demonstrating 
      pharmacokinetic equivalence. Decreases in free IgE and increases in total IgE 
      serum concentrations were comparable across groups. CT-P39 was well tolerated. 
      Safety endpoints were comparable across groups: there were no treatment-related 
      serious adverse events, deaths, or discontinuations due to treatment-emergent 
      adverse events. CONCLUSIONS: CT-P39 was well tolerated and demonstrated 
      pharmacokinetic equivalence with EU-omalizumab and US-omalizumab following 
      administration of a single dose in healthy individuals.
CI  - (c) 2022 The Authors. Clinical and Translational Allergy published by John Wiley 
      and Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.
FAU - Maurer, Marcus
AU  - Maurer M
AUID- ORCID: 0000-0002-4121-481X
AD  - Institute of Allergology, Charite - Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany.
AD  - Allergology and Immunology, Fraunhofer Institute for Translational Medicine and 
      Pharmacology (ITMP), Berlin, Germany.
FAU - Saini, Sarbjit S
AU  - Saini SS
AUID- ORCID: 0000-0001-8522-2742
AD  - Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, 
      Maryland, USA.
FAU - McLendon, Kristi
AU  - McLendon K
AD  - Nucleus Network Pty Ltd, Herston, Queensland, Australia.
FAU - Wabnitz, Paul
AU  - Wabnitz P
AUID- ORCID: 0000-0002-0820-9509
AD  - cPHARMA Pty Ltd, Adelaide, South Australia, Australia.
FAU - Kim, Sunghyun
AU  - Kim S
AD  - Celltrion, Inc., Incheon, Republic of Korea.
FAU - Ahn, Keumyoung
AU  - Ahn K
AD  - Celltrion, Inc., Incheon, Republic of Korea.
FAU - Kim, Suyoung
AU  - Kim S
AD  - Celltrion, Inc., Incheon, Republic of Korea.
FAU - Lee, Sewon
AU  - Lee S
AD  - Celltrion, Inc., Incheon, Republic of Korea.
FAU - Grattan, Clive
AU  - Grattan C
AUID- ORCID: 0000-0002-8466-4351
AD  - St John's Institute of Dermatology, Guy's Hospital, London, UK.
LA  - eng
GR  - Celltrion, Inc./
PT  - Journal Article
PL  - England
TA  - Clin Transl Allergy
JT  - Clinical and translational allergy
JID - 101576043
PMC - PMC9665328
OTO - NOTNLM
OT  - CT-P39
OT  - biosimilar
OT  - immunoglobulin E
OT  - omalizumab
OT  - pharmacokinetics
COIS- Marcus Maurer reports current or recent speaker and/or advisory roles for and/or 
      has received research funding from Allakos, Amgen, Aralez, Argenx, AstraZeneca, 
      Celldex, Celltrion, Centogene, CSL Behring, FAES, Genentech, GIInnovation, Innate 
      Pharma, Kyowa Kirin, Leo Pharma, Lilly, Menarini, Moxie, Novartis, Roche, 
      Sanofi/Regeneron, ThirdHarmonicBio, UCB, and Uriach. Sarbjit S. Saini reports 
      research interests for Amgen, National Institutes of Health, Novartis, Regeneron, 
      and Sanofi; and consultancies for Allakos, Aquestive, Celltrion, Escient, 
      Granular Therapeutics, Innate, Novartis, Regeneron, and Sanofi. Sunghyun Kim, 
      Keumyoung Ahn, Suyoung Kim, and Sewon Lee are employees of Celltrion, Inc. Clive 
      Grattan reports consultancies for Argenx, Blueprint Medicines, Celltrion, Inc., 
      Novartis, and Sanofi. Kristi McLendon and Paul Wabnitz have no conflicts of 
      interest to declare.
EDAT- 2022/11/27 06:00
MHDA- 2022/11/27 06:01
PMCR- 2022/11/15
CRDT- 2022/11/26 11:57
PHST- 2022/08/17 00:00 [revised]
PHST- 2022/06/06 00:00 [received]
PHST- 2022/09/18 00:00 [accepted]
PHST- 2022/11/26 11:57 [entrez]
PHST- 2022/11/27 06:00 [pubmed]
PHST- 2022/11/27 06:01 [medline]
PHST- 2022/11/15 00:00 [pmc-release]
AID - CLT212204 [pii]
AID - 10.1002/clt2.12204 [doi]
PST - ppublish
SO  - Clin Transl Allergy. 2022 Nov;12(11):e12204. doi: 10.1002/clt2.12204.