Conaghan, PG orcid.org/0000-0002-3478-5665, Bowes, MA, Kingsbury, SR orcid.org/0000-0002-9917-1269 et al. (9 more authors) (2020) Disease-Modifying Effects of a Novel Cathepsin K Inhibitor in Osteoarthritis: A Randomized Controlled Trial. Annals of Internal Medicine, 172 (2). pp. 86-95. ISSN 0003-4819
Abstract
Background:
MIV-711 is a novel selective cathepsin K inhibitor with beneficial effects on bone and cartilage in preclinical osteoarthritis models.
Objective:
To evaluate the efficacy, safety, and tolerability of MIV-711 in participants with symptomatic, radiographic knee osteoarthritis.
Design:
26-week randomized, double-blind, placebo-controlled phase 2a study with a 26-week open-label safety extension substudy. (EudraCT: 2015-003230-26 and 2016-001096-73)
Setting:
Six European sites.
Participants:
244 participants with primary knee osteoarthritis, Kellgren–Lawrence grade 2 or 3, and pain score of 4 to 10 on a numerical rating scale (NRS).
Intervention:
MIV-711, 100 (n = 82) or 200 (n = 81) mg daily, or matched placebo (n = 77). Participants (46 who initially received 200 mg/d and 4 who received placebo) received 200 mg of MIV-711 daily during the extension substudy.
Measurements:
The primary outcome was change in NRS pain score. The key secondary outcome was change in bone area on magnetic resonance imaging (MRI). Other secondary end points included cartilage thickness on quantitative MRI and type I and II collagen C-telopeptide biomarkers. Outcomes were assessed over 26 weeks.
Results:
Changes in NRS pain scores with MIV-711 were not statistically significant (placebo, −1.4; MIV-711, 100 mg/d, −1.7; MIV-711, 200 mg/d, −1.5). MIV-711 significantly reduced medial femoral bone area progression (P = 0.002 for 100 mg/d and 0.004 for 200 mg/d) and medial femoral cartilage thinning (P = 0.023 for 100 mg/d and 0.125 for 200 mg/d) versus placebo and substantially reduced bone and cartilage biomarker levels. Nine serious adverse events occurred in 6 participants (1 in the placebo group, 3 in the 100 mg group, and 2 in the 200 mg group); none were considered to be treatment-related.
Limitation:
The trial was relatively short.
Conclusion:
MIV-711 was not more effective than placebo for pain, but it significantly reduced bone and cartilage progression with a reassuring safety profile. This treatment may merit further evaluation as a disease-modifying osteoarthritis drug.
Primary Funding Source:
Medivir.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 American College of Physicians. All Rights Reserved. This is an author produced version of an article published in Annals of Internal Medicine. Reproduced with permission from the publisher. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Musculoskeletal Medicine & Imaging (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 05 Nov 2019 13:42 |
Last Modified: | 26 Aug 2020 11:13 |
Status: | Published |
Publisher: | American College of Physicians |
Identification Number: | 10.7326/M19-0675 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:153052 |