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Administration of an adeno-associated viral vector expressing interferon-β in patients with inflammatory hand arthritis, results of a phase I/II study.
- Source :
- Osteoarthritis & Cartilage; Jan2022, Vol. 30 Issue 1, p52-60, 9p
- Publication Year :
- 2022
-
Abstract
- <bold>Objective: </bold>Inflammatory hand arthritis (IHA) results in impaired function. Local gene therapy with ART-I02, a recombinant adeno-associated virus (AAV) serotype 5 vector expressing interferon (IFN)-β, under the transcriptional control of nuclear factor κ-B responsive promoter, was preclinically shown to have favorable effects. This study aimed to investigate the safety and tolerability of local gene therapy with ART-I02 in patients with IHA.<bold>Methods: </bold>In this first-in-human, dose-escalating, cohort study, 12 IHA patients were to receive a single intra-articular (IA) injection of ART-I02 ranging 0.3 × 1012-1.2 × 1013 genome copies in an affected hand joint. Adverse events (AEs), routine safety laboratory and the clinical course of disease were periodically evaluated. Baseline- and follow-up contrast enhanced magnetic resonance images (MRIs), shedding of viral vectors in bodily fluids, and AAV5 and IFN-β immune responses were evaluated. A data review committee provided safety recommendations.<bold>Results: </bold>Four patients were enrolled. Long-lasting local AEs were observed in 3 patients upon IA injection of ART-I02. The AEs were moderate in severity and could be treated conservative. Given the duration of the AEs and their possible or probable relation to ART-I02, no additional patients were enrolled. No systemic treatment emergent AEs were observed. The MRIs reflected the AEs by (peri)arthritis. No T-cell response against AAV5 or IFN-β, nor IFN-β antibodies could be detected. Neutralizing antibody titers against AAV5 raised post-dose.<bold>Conclusion: </bold>Single IA doses of 0.6 × 1012 or 1.2 × 1012 ART-I02 vector genomes were administered without systemic side effects or serious AEs. However, local tolerability was insufficient for continuation.<bold>Trial Registration: </bold>NCT02727764. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10634584
- Volume :
- 30
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- Osteoarthritis & Cartilage
- Publication Type :
- Academic Journal
- Accession number :
- 154268546
- Full Text :
- https://doi.org/10.1016/j.joca.2021.09.013