TLC599 in patients with osteoarthritis of the knee: a phase IIa, randomized, placebo-controlled, dose-finding study

<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>Corticosteroid injection for knee osteoarthritis is limited by its modest duration of treatment effect. The liposome formulation of dexamethasone sodium phosphate (TLC599) was developed for the sustained relief of osteoarthritis pain. This clinical study was conducted to evaluate the efficacy and safety of TLC599 at two dose levels in patients with knee osteoarthritis.</jats:p>
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<jats:title>Methods</jats:title>
<jats:p>A randomized, double-blinded, placebo-controlled study was conducted in 75 patients with osteoarthritis of the knee from 13 study centers. Patients were randomized and administered a single intra-articular injection of TLC599 or placebo and assessed for efficacy and safety for 24 weeks. Patient-reported outcomes included the Western Ontario and McMaster Universities Arthritis (WOMAC) Index for pain and function and visual analog scale for pain.</jats:p>
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<jats:title>Results</jats:title>
<jats:p>TLC599 at 12 mg demonstrated significantly greater reduction in WOMAC pain through 12 weeks (least squares (LS) mean difference = − 0.37, <jats:italic>p</jats:italic> = 0.0027) and through 24 weeks (LS mean difference = − 0.35, <jats:italic>p</jats:italic> = 0.0037) when compared to placebo. TLC599 12 mg also exhibited significantly greater improvement in function when compared to placebo at 24 weeks (LS mean difference = − 0.26, <jats:italic>p</jats:italic> = 0.0457). TLC599 18 mg did not significantly improve pain or function in comparison with placebo. The use of acetaminophen during the study was less in both TLC599 groups in comparison with placebo. No major or unexpected safety issues were reported.</jats:p>
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<jats:title>Conclusions</jats:title>
<jats:p>In participants with symptomatic knee osteoarthritis, TLC599 is a well-tolerated treatment that reduces pain and improves function for up to 24 weeks, a longer duration than that reported for existing IA treatments.</jats:p>
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<jats:title>Trial registration</jats:title>
<jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://clinicaltrials.gov">ClinicalTrials.gov</jats:ext-link>, <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT03005873?term=TLC599&draw=2&rank=3">NCT03005873</jats:ext-link>. Registered on 29 December 2016</jats:p>
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