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Symptomatic and structural benefit of cathepsin K inhibition by MIV-711 in a subgroup with unilateral pain: post-hoc analysis of a randomised phase 2a clinical trial


1, 2, 3, 4, 5, 6, 7

 

  1. NBCD A/S, Herlev, Denmark. abi@nbcd.com
  2. NBCD A/S, Herlev, Denmark.
  3. NBCD A/S, Herlev, Denmark.
  4. Medivir AB, Huddinge, Sweden.
  5. Medivir AB, Huddinge, Sweden.
  6. iMorphics, Manchester, UK.
  7. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Biomedical Research Centre, Leeds, UK.

CER15118
2022 Vol.40, N°5
PI 1034, PF 1037
Brief Paper

purchase article

PMID: 35238765 [PubMed]

Received: 30/08/2021
Accepted : 23/11/2021
In Press: 25/02/2022
Published: 13/05/2022

Abstract

OBJECTIVES:
Osteoarthritis (OA) development programmes face challenges due to discordance between structural changes and symptoms. A novel cathepsin-K inhibitor, MIV-711, recently reported structural benefits, but did not demonstrate a significant difference from placebo in symptoms. Previous work suggests that pain from non-target joints may confound OA pain outcomes. We therefore conducted an exploratory analysis in participants with predominantly unilateral knee pain from the MIV-711-201 trial. METHOSD: Participants scoring below median contralateral knee NRS pain at baseline from the MIV-711-201 phase 2a clinical trial (n=119) were analysed by treatment group for differences in change from baseline in WOMAC pain, quantitative magnetic resonance imaging bone area and cartilage thickness with a repeated-measures mixed model adjusting for relevant co-variates.
RESULTS:
In the subgroup with unilateral knee pain, treatment with MIV-711 100 mg led to greater reduction in WOMAC pain compared to placebo (-5.0, 95% CI: -8.69 to -1.3, p=0.008), while 200 mg did not (-2.5, 95% CI: -6.5 to 1.6, p=0.23). MIV-711 treatment was associated with a reduced change in bone area compared to placebo (200 mg; -19.6 mm2 , 95% CI: -36.2 to -3.0, p=0.02, and 100 mg; -12.5 mm2 , 95% CI: -27.8 to 2.8, p=0.11,). No observed differences between treatment groups in cartilage thickness were found in this subgroup.
CONCLUSIONS:
In a subgroup with predominantly unilateral knee pain, significant reduction in OA pain by MIV-711 100 mg treatment was found, with concurrent beneficial structural effects, highlighting the importance of appropriate pain inclusion criteria in OA trials.

DOI: https://doi.org/10.55563/clinexprheumatol/1kvgte

Rheumatology Article

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