AI Article Synopsis
- MIV-711 is a selective cathepsin K inhibitor that showed potential benefits for bone and cartilage in osteoarthritis models, and this study aimed to assess its efficacy and safety in knee osteoarthritis patients.
- The 26-week trial involved 244 participants, who were randomly assigned to receive either MIV-711 at 100 mg or 200 mg doses or a placebo, with the primary outcome focused on pain reduction measured by a numerical rating scale (NRS).
- While MIV-711 did not significantly reduce pain scores compared to placebo, it did show a significant decrease in bone area progression and cartilage thinning, with few serious adverse events noted that weren't deemed treatment-related.
Article 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.
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| http://dx.doi.org/10.7326/M19-0675 | DOI Listing |
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