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.

Authors

Stanley Cohen, Marc C Hochberg, Alan Kivitz, Nino Joy, J Derek Jackson, Mi-Jeong Kim, Lucia Sanchez-Gonzalez, Mary DiGiorgi, Jonathan Slonin, Philip G Conaghan

Published in

Annals of the rheumatic diseases. Aug 04, 2026. Epub Aug 04, 2026.

Abstract

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.
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.
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.
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.

PMID:
42552219
Bibliographic data and abstract were imported from PubMed on 05 Aug 2026.

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