Administration of an adeno-associated viral vector expressing interferon-β in patients with inflammatory hand arthritis, results of a phase I/II study

Osteoarthritis Cartilage. 2022 Jan;30(1):52-60. doi: 10.1016/j.joca.2021.09.013. Epub 2021 Oct 6.


Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Trial registration: NCT02727764.

Keywords: AAV5; Gene therapy; IFN-β; Osteoarthritis; Rheumatoid arthritis.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arthritis / therapy*
  • Cohort Studies
  • Dependovirus* / metabolism
  • Female
  • Genetic Therapy / adverse effects
  • Genetic Therapy / methods*
  • Genetic Vectors*
  • Hand Joints*
  • Humans
  • Interferon-beta / administration & dosage*
  • Interferon-beta / biosynthesis
  • Middle Aged


  • Interferon-beta

Supplementary concepts

  • Adeno-associated virus-5

Associated data