Session Type: ACR Late-breaking Abstract Session
Session Time: 9:00AM-11:00AM
The need for drugsthat achieve structure modification in OA is imminent but their development hasbeen burdened by the need for large, long term studies. New imaging biomarkersusing structured machine learning offer opportunity for shorter duration andsmaller DMOAD trials. MIV-711, a potent and selective cathepsin K inhibitor reducedCTX-I and CTX-II after once-daily administration for up to 28 days in healthyvolunteers. Our aim was to examine the efficacy (symptoms and structure) andsafety of MIV-711 in knee OA patients.
Patients with ACR knee OA, KL2-3 and pain≥4 & <10 on 0-10 NRS were enrolled at one of 6 European sites andrandomised to receive MIV-711 100mg or 200mg or matched placebo qd. Participantsremained on usual analgesic medication. Clinical (pain, function, QoL) andsafety data were recorded serially and MRI was performed at baseline and wk26. Primaryoutcome was change in NRS pain score with the key secondary endpoint of changein MRI bone area (medial femur). The main analyses were conducted using linearmixed models.
244 participants were enrolled (100mg n=82,200mg n=82, placebo n=80), 69% women, mean age 62, mean BMI ~32. NRS pain scores;function and QoL measures were not statistically significantly reduced comparedto placebo. However, there was a trend to reduction for MIV-711 on the NRS (Figure1) and across the majority of patient-reported outcomes. Significant reductionin medial femur bone area change for both MIV-711 doses (unadjusted p-values =0.002and 0.004) were observed at wk26, with no evident differences between the 2doses (Figure 2A). MIV-711 treated participants demonstrated reduced loss ofcartilage thickness on the medial femur versus placebo (unadjusted p=0.023 for100mg dose, 0.125 for 200mg dose, Figure 2B); medial tibia cartilage loss wasnot significant. The reductions observed for the biomarkers CTX-I and –II weresubstantial and of a similar magnitude, indicating strong target engagement forboth doses. There was generally good tolerability and safety, with infrequent musculoskeletalsymptoms, infections and rashes.
MIV-711 demonstrated significant reductionin OA bone disease progression, and also reduced cartilage progression, in thefemur. Although there was no statistically significant reduction in pain, thestudy duration required to fully realize the symptom benefits expected fromstructure modification is unclear. Further evaluation of this novel agent isnow warranted.
To cite this abstract in AMA style:Conaghan PG, Bowes MA, Kingsbury SR, Brett A, Guillard G, Jansson Å, Wadell C, Bethell R, Öhd J. Miv-711, a Novel Cathepsin K Inhibitor Demonstrates Evidence of Osteoarthritis Structure Modification: Results from a 6 Month Randomized Double-Blind Placebo-Controlled Phase IIA Trial [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/miv-711-a-novel-cathepsin-k-inhibitor-demonstrates-evidence-of-osteoarthritis-structure-modification-results-from-a-6-month-randomized-double-blind-placebo-controlled-phase-iia-trial/. Accessed November 18, 2017.
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ACR Meeting Abstracts - http://acrabstracts.org/abstract/miv-711-a-novel-cathepsin-k-inhibitor-demonstrates-evidence-of-osteoarthritis-structure-modification-results-from-a-6-month-randomized-double-blind-placebo-controlled-phase-iia-trial/