Safety, biodistribution, and exploratory clinical outcomes of a novel intra-articular IL-1Ra gene therapy (PCRX-201) in moderate-to-severe knee osteoarthritis: 2-year results of a phase 1 study
5 affiliations
- 1Metroplex Clinical Research Center, Dallas, TX, USA. Electronic address: [email protected]
- 2University of Maryland School of Medicine, Departments of Medicine and Epidemiology and Public Health, Baltimore, MD, USA
- 3Altoona Center for Clinical Research, Duncansville, PA, USA
- 4Pacira BioSciences, Inc, Brisbane, CA, USA
- 5The National Institute for Health and Care Research (NIHR) Leeds Biomedical Research Centre, Leeds Institute of Rheumatic & Musculoskeletal Medicine, University of Leeds, Leeds, UK
Abstract
OBJECTIVES: The objective of this study is to investigate the safety, biodistribution, and exploratory clinical outcomes of enekinragene inzadenovec (PCRX-201), a high-capacity, nonintegrating, nonreplicating adenovirus serotype 5 vector expressing interleukin-1 receptor antagonist under the control of an inflammation-inducible promoter, in patients with moderate-to-severe knee osteoarthritis. METHODS: This open-label phase 1 trial (NCT04119687) enrolled participants aged 30 to 80 years with symptomatic (Western Ontario and McMaster Universities Osteoarthritis [WOMAC] pain score ≥ 5 and ≤ 9 [0-10-point scale]) and radiographic (Kellgren-Lawrence grade 2-4) knee osteoarthritis. In part 1, participants received a single intra-articular injection of PCRX-201 at 1 of 3 doses (n = 36). In part 2, participants received intra-articular methylprednisolone acetate immediately before PCRX-201 at the same dose (n = 36). Outcomes at week 104 included safety (primary endpoint), biodistribution (secondary endpoint), clinical outcomes (exploratory patient-reported endpoint), and immunogenicity. Data were analysed as observed. RESULTS: Transient treatment-related knee effusion was the most common adverse event and occurred less frequently in participants receiving glucocorticoid pretreatment (13/36 [36.1%]) than in those who did not (22/36 [61.1%]). Very limited biodistribution was detected outside the knee; only 2 participants had detectable PCRX-201 in plasma on days 1 and 4 postinjection. By week 104, 33/72 (45.8%) of participants had discontinued the study; however, those remaining showed sustained improvements with PCRX-201 for the exploratory outcomes of pain, stiffness, and function across doses and groups, regardless of preexisting neutralising antibody levels, with greater improvements observed in the glucocorticoid-pretreated group. CONCLUSIONS: A single intra-articular injection of PCRX-201 demonstrated safety and localised distribution within the knee. Exploratory patient-reported clinical outcomes suggest promise and support further investigation of PCRX-201.
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BibTeX
@article{cohen2026safety,
title = {{Safety, biodistribution, and exploratory clinical outcomes of a novel intra-articular IL-1Ra gene therapy (PCRX-201) in moderate-to-severe knee osteoarthritis: 2-year results of a phase 1 study}},
author = {Stanley B. Cohen and Marc C. Hochberg and Alan Kivitz and Nino Gogitidze Joy and J. Derek Jackson and Mi-Jeong Kim and Lucía Sanchez-Gonzalez and Mary DiGiorgi and Jonathan Slonin and Philip G. Conaghan},
journal = {Annals of the Rheumatic Diseases},
year = {2026},
month = aug,
doi = {10.1016/j.ard.2026.06.034},
url = {https://doi.org/10.1016/j.ard.2026.06.034},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Safety, biodistribution, and exploratory clinical outcomes of a novel intra-articular IL-1Ra gene therapy (PCRX-201) in moderate-to-severe knee osteoarthritis: 2-year results of a phase 1 study
AU - Stanley B. Cohen
AU - Marc C. Hochberg
AU - Alan Kivitz
AU - Nino Gogitidze Joy
AU - J. Derek Jackson
AU - Mi-Jeong Kim
AU - Lucía Sanchez-Gonzalez
AU - Mary DiGiorgi
AU - Jonathan Slonin
AU - Philip G. Conaghan
PY - 2026
DA - 2026/08/01
JO - Annals of the Rheumatic Diseases
DO - 10.1016/j.ard.2026.06.034
UR - https://doi.org/10.1016/j.ard.2026.06.034
AB - OBJECTIVES: The objective of this study is to investigate the safety, biodistribution, and exploratory clinical outcomes of enekinragene inzadenovec (PCRX-201), a high-capacity, nonintegrating, nonreplicating adenovirus serotype 5 vector expressing interleukin-1 receptor antagonist under the control of an inflammation-inducible promoter, in patients with moderate-to-severe knee osteoarthritis. METHODS: This open-label phase 1 trial (NCT04119687) enrolled participants aged 30 to 80 years with symptomatic (Western Ontario and McMaster Universities Osteoarthritis [WOMAC] pain score ≥ 5 and ≤ 9 [0-10-point scale]) and radiographic (Kellgren-Lawrence grade 2-4) knee osteoarthritis. In part 1, participants received a single intra-articular injection of PCRX-201 at 1 of 3 doses (n = 36). In part 2, participants received intra-articular methylprednisolone acetate immediately before PCRX-201 at the same dose (n = 36). Outcomes at week 104 included safety (primary endpoint), biodistribution (secondary endpoint), clinical outcomes (exploratory patient-reported endpoint), and immunogenicity. Data were analysed as observed. RESULTS: Transient treatment-related knee effusion was the most common adverse event and occurred less frequently in participants receiving glucocorticoid pretreatment (13/36 [36.1%]) than in those who did not (22/36 [61.1%]). Very limited biodistribution was detected outside the knee; only 2 participants had detectable PCRX-201 in plasma on days 1 and 4 postinjection. By week 104, 33/72 (45.8%) of participants had discontinued the study; however, those remaining showed sustained improvements with PCRX-201 for the exploratory outcomes of pain, stiffness, and function across doses and groups, regardless of preexisting neutralising antibody levels, with greater improvements observed in the glucocorticoid-pretreated group. CONCLUSIONS: A single intra-articular injection of PCRX-201 demonstrated safety and localised distribution within the knee. Exploratory patient-reported clinical outcomes suggest promise and support further investigation of PCRX-201.
SN - 0003-4967
SN - 1468-2060
ER -