Evaluation of S201086/GLPG1972, an ADAMTS-5 inhibitor, for the treatment of knee osteoarthritis in ROCCELLA: a phase 2 randomized clinical trial

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  • T. Schnitzer
  • M. Pueyo
  • H. Deckx
  • E. van der Aar
  • K. Bernard
  • S. Hatch
  • M. van der Stoep
  • S. Grankov
  • D. Phung
  • O. Imbert
  • D. Chimits
  • K. Muller
  • M. C. Hochberg
  • Bliddal, Henning
  • W. Wirth
  • F. Eckstein
  • P. G. Conaghan

Objective: To evaluate the efficacy and safety of the anti-catabolic ADAMTS-5 inhibitor S201086/GLPG1972 for the treatment of symptomatic knee osteoarthritis. Design: ROCCELLA (NCT03595618) was a randomized, double-blind, placebo-controlled, dose-ranging, phase 2 trial in adults (aged 40–75 years) with knee osteoarthritis. Participants had moderate-to-severe pain in the target knee, Kellgren–Lawrence grade 2 or 3 and Osteoarthritis Research Society International joint space narrowing (grade 1 or 2). Participants were randomized 1:1:1:1 to once-daily oral S201086/GLPG1972 75, 150 or 300 mg, or placebo for 52 weeks. The primary endpoint was change from baseline to week 52 in central medial femorotibial compartment (cMFTC) cartilage thickness assessed quantitatively by magnetic resonance imaging. Secondary endpoints included change from baseline to week 52 in radiographic joint space width, Western Ontario and McMaster Universities Osteoarthritis Index total and subscores, and pain (visual analogue scale). Treatment-emergent adverse events (TEAEs) were also recorded. Results: Overall, 932 participants were enrolled. No significant differences in cMFTC cartilage loss were observed between placebo and S201086/GLPG1972 therapeutic groups: placebo vs 75 mg, P = 0.165; vs 150 mg, P = 0.939; vs 300 mg, P = 0.682. No significant differences in any of the secondary endpoints were observed between placebo and treatment groups. Similar proportions of participants across treatment groups experienced TEAEs. Conclusions: Despite enrolment of participants who experienced substantial cartilage loss over 52 weeks, during the same time period, S201086/GLPG1972 did not significantly reduce rates of cartilage loss or modify symptoms in adults with symptomatic knee osteoarthritis.

OriginalsprogEngelsk
TidsskriftOsteoarthritis and Cartilage
Vol/bind31
Udgave nummer7
Sider (fra-til)985-994
Antal sider10
ISSN1063-4584
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
TS has received consultancy fees from AstraZeneca , Collegium , Galapagos NV , GSK , Lilly , Pfizer and Vertex , and is an employee of Northwestern University Feinberg School of Medicine, which has also received fees from Galapagos NV. MP, KB, SG, OI and DC are employees of Institut de Recherches Internationales Servier (IRIS). EvdA, MvdS, DP and KM are employees and shareholders of Galapagos NV. HD and SH were employees and shareholders of Galapagos NV at the time of the study. MCH has received consultancy fees from Acadia Pharmaceuticals , Bioclinica , BriOri Biotech , Eli Lilly , Flexion Therapeutics Inc. , GSK, Novartis Pharma AG , Pfizer Inc and Theralogix LLC , and was a member of the ROCCELLA Data and Safety Monitoring Board. HB has received research grants from Galapagos NV . The Parker Institute, Bispebjerg, and Frederiksberg Hospital are supported by a core grant from the Oak Foundation ( OCAY-18-774-OFIL ). WW is a part-time employee and shareholder of Chondrometrics, and has received personal fees from Galapagos NV . FE has received grants from Galapagos NV and personal fees from AbbVie , Galapagos NV , HealthLink , ICM , IRIS , Kolon TissueGene , Merck KGaA , Novartis , Roche and Samumed . PGC has received consultancy fees from AbbVie , BMS , EMD Serono , Flexion Therapeutics , Galapagos , GSK , Gilead , Novartis , Pfizer , Regeneron , Stryker and UCB ; and speakers fees from AbbVie , Galapagos and Pfizer .

Funding Information:
This study was funded by Galapagos NV and IRIS. Medical writing support was provided by Maxine Cox and Frances Thompson of PharmaGenesis London, London, UK and was funded by Galapagos NV and IRIS , in accordance with Good Publication Practice guidelines . PGC is supported in part through the UK National Institute for Health and Care Research (NIHR) Leeds Biomedical Research Centre . The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR or the Department of Health.

Publisher Copyright:
© 2023 The Authors

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