Utilizing PK and PD Biomarkers to Guide the First-in-Human Starting Dose Selection of MTBT1466A: A Novel Humanized Monoclonal Anti-TGFβ3 Antibody for the Treatment of Fibrotic Diseases.
Anti-TGFβ3
Biomarker
Fibrotic diseases
First-in-human clinical trial
Gene expression
Healthy volunteers
Pharmacokinetics and pharmacodymics
Starting dose selection
Journal
Journal of pharmaceutical sciences
ISSN: 1520-6017
Titre abrégé: J Pharm Sci
Pays: United States
ID NLM: 2985195R
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
11
05
2023
revised:
03
07
2023
accepted:
03
07
2023
pubmed:
11
7
2023
medline:
11
7
2023
entrez:
10
7
2023
Statut:
ppublish
Résumé
MTBT1466A is a high-affinity TGFβ3-specific humanized IgG1 monoclonal antibody with reduced Fc effector function, currently under investigation in clinical trials as a potential anti-fibrotic therapy. Here, we characterized the pharmacokinetics (PK) and pharmacodynamics (PD) of MTBT1466A in mice and monkeys and predicted the PK/PD of MTBT1466A in humans to guide the selection of the first-in-human (FIH) starting dose. MTBT1466A demonstrated a typical IgG1-like biphasic PK profile in monkeys, and the predicted human clearance of 2.69 mL/day/kg and t
Identifiants
pubmed: 37429356
pii: S0022-3549(23)00279-4
doi: 10.1016/j.xphs.2023.07.005
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2910-2920Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.