First-in-human, double-blind, randomized phase 1b study of peptide immunotherapy IMCY-0098 in new-onset type 1 diabetes: an exploratory analysis of immune biomarkers.
Beta cells
Exploratory analysis
Immune biomarker machine learning
Immunotherapy
T cells
Type 1 diabetes
Journal
BMC medicine
ISSN: 1741-7015
Titre abrégé: BMC Med
Pays: England
ID NLM: 101190723
Informations de publication
Date de publication:
21 Jun 2024
21 Jun 2024
Historique:
received:
06
12
2023
accepted:
11
06
2024
medline:
21
6
2024
pubmed:
21
6
2024
entrez:
20
6
2024
Statut:
epublish
Résumé
IMCY-0098, a synthetic peptide developed to halt disease progression via elimination of key immune cells in the autoimmune cascade, has shown a promising safety profile for the treatment of type 1 diabetes (T1D) in a recent phase 1b trial. This exploratory analysis of data from that trial aimed to identify the patient biomarkers at baseline associated with a positive response to treatment and examined the associations between immune response parameters and clinical efficacy endpoints (as surrogates for mechanism of action endpoints) using an artificial intelligence-based approach of unsupervised explainable machine learning. We conducted an exploratory analysis of data from a phase 1b, dose-escalation, randomized, placebo-controlled study of IMCY-0098 in patients with recent-onset T1D. Here, a panel of markers of T cell activation, memory T cells, and effector T cell response were analyzed via descriptive statistics. Artificial intelligence-based analyses of associations between all variables, including immune responses and clinical responses, were performed using the Knowledge Extraction and Management (KEM The relationship between all available patient data was investigated using unsupervised machine learning implemented in the KEM Promising preliminary efficacy results support the design of a phase 2 study of IMCY-0098 in patients with recent-onset T1D. ClinicalTrials.gov NCT03272269; EudraCT: 2016-003514-27.
Sections du résumé
BACKGROUND
BACKGROUND
IMCY-0098, a synthetic peptide developed to halt disease progression via elimination of key immune cells in the autoimmune cascade, has shown a promising safety profile for the treatment of type 1 diabetes (T1D) in a recent phase 1b trial. This exploratory analysis of data from that trial aimed to identify the patient biomarkers at baseline associated with a positive response to treatment and examined the associations between immune response parameters and clinical efficacy endpoints (as surrogates for mechanism of action endpoints) using an artificial intelligence-based approach of unsupervised explainable machine learning.
METHODS
METHODS
We conducted an exploratory analysis of data from a phase 1b, dose-escalation, randomized, placebo-controlled study of IMCY-0098 in patients with recent-onset T1D. Here, a panel of markers of T cell activation, memory T cells, and effector T cell response were analyzed via descriptive statistics. Artificial intelligence-based analyses of associations between all variables, including immune responses and clinical responses, were performed using the Knowledge Extraction and Management (KEM
RESULTS
RESULTS
The relationship between all available patient data was investigated using unsupervised machine learning implemented in the KEM
CONCLUSIONS
CONCLUSIONS
Promising preliminary efficacy results support the design of a phase 2 study of IMCY-0098 in patients with recent-onset T1D.
TRIAL REGISTRATION
BACKGROUND
ClinicalTrials.gov NCT03272269; EudraCT: 2016-003514-27.
Identifiants
pubmed: 38902652
doi: 10.1186/s12916-024-03476-y
pii: 10.1186/s12916-024-03476-y
doi:
Substances chimiques
Biomarkers
0
Peptides
0
Banques de données
ClinicalTrials.gov
['NCT03272269']
Types de publication
Journal Article
Randomized Controlled Trial
Clinical Trial, Phase I
Langues
eng
Sous-ensembles de citation
IM
Pagination
259Informations de copyright
© 2024. The Author(s).
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