A Phase 2b randomized trial of lorecivivint, a novel intra-articular CLK2/DYRK1A inhibitor and Wnt pathway modulator for knee osteoarthritis
Lorecivivint (LOR; SM04690), an investigational Wnt pathway modulator, previously demonstrated patient-reported and radiographic outcome improvements vs placebo in clinically relevant subjects with moderate to severe knee osteoarthritis (OA). This study's objective was to identify effective LOR...
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| Published in | Osteoarthritis and cartilage Vol. 29; no. 5; pp. 654 - 666 |
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| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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England
Elsevier Ltd
01.05.2021
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| Abstract | Lorecivivint (LOR; SM04690), an investigational Wnt pathway modulator, previously demonstrated patient-reported and radiographic outcome improvements vs placebo in clinically relevant subjects with moderate to severe knee osteoarthritis (OA). This study's objective was to identify effective LOR doses.
Subjects in this 24-week, Phase 2b, multicenter, randomized, double-blind, placebo (PBO)-controlled trial received an intra-articular injection of 2 mL LOR (0.03, 0.07, 0.15, or 0.23 mg), PBO, or dry-needle sham. The primary efficacy endpoints were changes in Pain NRS [0–10], WOMAC Pain [0–100], WOMAC Function [0–100], and radiographic mJSW outcomes, which were measured using baseline-adjusted analysis of covariance at Week 24. Multiple Comparison Procedure-Modeling (MCP-Mod) was performed for dose modeling.
In total, 695/700 subjects were treated. Pain NRS showed significant improvements vs PBO after treatment with 0.07 mg and 0.23 mg LOR at Weeks 12 (−0.96, 95% CI [−1.54, −0.37], P = 0.001; −0.78 [−1.39, −0.17], P = 0.012) and 24 (−0.70 [-1.34, −0.06], P = 0.031; −0.82 [−1.51, −0.12], P = 0.022). Additionally, 0.07 mg LOR significantly improved WOMAC Pain and Function subscores vs PBO at Week 12 (P = 0.04, P = 0.021), and 0.23 mg LOR significantly improved both WOMAC subscores at Week 24 (P = 0.031, P = 0.017). No significant differences from PBO were observed for other doses. No radiographic progression was observed in any group at Week 24. MCP-Mod identified 0.07 mg LOR as the lowest effective dose.
This 24-week Phase 2b trial demonstrated the efficacy of LOR on PROs in knee OA subjects. The optimal dose for future studies was identified as 0.07 mg LOR. |
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| AbstractList | Lorecivivint (LOR; SM04690), an investigational Wnt pathway modulator, previously demonstrated patient-reported and radiographic outcome improvements vs placebo in clinically relevant subjects with moderate to severe knee osteoarthritis (OA). This study's objective was to identify effective LOR doses.
Subjects in this 24-week, Phase 2b, multicenter, randomized, double-blind, placebo (PBO)-controlled trial received an intra-articular injection of 2 mL LOR (0.03, 0.07, 0.15, or 0.23 mg), PBO, or dry-needle sham. The primary efficacy endpoints were changes in Pain NRS [0–10], WOMAC Pain [0–100], WOMAC Function [0–100], and radiographic mJSW outcomes, which were measured using baseline-adjusted analysis of covariance at Week 24. Multiple Comparison Procedure-Modeling (MCP-Mod) was performed for dose modeling.
In total, 695/700 subjects were treated. Pain NRS showed significant improvements vs PBO after treatment with 0.07 mg and 0.23 mg LOR at Weeks 12 (−0.96, 95% CI [−1.54, −0.37], P = 0.001; −0.78 [−1.39, −0.17], P = 0.012) and 24 (−0.70 [-1.34, −0.06], P = 0.031; −0.82 [−1.51, −0.12], P = 0.022). Additionally, 0.07 mg LOR significantly improved WOMAC Pain and Function subscores vs PBO at Week 12 (P = 0.04, P = 0.021), and 0.23 mg LOR significantly improved both WOMAC subscores at Week 24 (P = 0.031, P = 0.017). No significant differences from PBO were observed for other doses. No radiographic progression was observed in any group at Week 24. MCP-Mod identified 0.07 mg LOR as the lowest effective dose.
This 24-week Phase 2b trial demonstrated the efficacy of LOR on PROs in knee OA subjects. The optimal dose for future studies was identified as 0.07 mg LOR. SummaryObjectiveLorecivivint (LOR; SM04690), an investigational Wnt pathway modulator, previously demonstrated patient-reported and radiographic outcome improvements vs placebo in clinically relevant subjects with moderate to severe knee osteoarthritis (OA). This study's objective was to identify effective LOR doses. DesignSubjects in this 24-week, Phase 2b, multicenter, randomized, double-blind, placebo (PBO)-controlled trial received an intra-articular injection of 2 mL LOR (0.03, 0.07, 0.15, or 0.23 mg), PBO, or dry-needle sham. The primary efficacy endpoints were changes in Pain NRS [0–10], WOMAC Pain [0–100], WOMAC Function [0–100], and radiographic mJSW outcomes, which were measured using baseline-adjusted analysis of covariance at Week 24. Multiple Comparison Procedure-Modeling (MCP-Mod) was performed for dose modeling. ResultsIn total, 695/700 subjects were treated. Pain NRS showed significant improvements vs PBO after treatment with 0.07 mg and 0.23 mg LOR at Weeks 12 (−0.96, 95% CI [−1.54, −0.37], P = 0.001; −0.78 [−1.39, −0.17], P = 0.012) and 24 (−0.70 [-1.34, −0.06], P = 0.031; −0.82 [−1.51, −0.12], P = 0.022). Additionally, 0.07 mg LOR significantly improved WOMAC Pain and Function subscores vs PBO at Week 12 ( P = 0.04, P = 0.021), and 0.23 mg LOR significantly improved both WOMAC subscores at Week 24 ( P = 0.031, P = 0.017). No significant differences from PBO were observed for other doses. No radiographic progression was observed in any group at Week 24. MCP-Mod identified 0.07 mg LOR as the lowest effective dose. ConclusionThis 24-week Phase 2b trial demonstrated the efficacy of LOR on PROs in knee OA subjects. The optimal dose for future studies was identified as 0.07 mg LOR. Lorecivivint (LOR; SM04690), an investigational Wnt pathway modulator, previously demonstrated patient-reported and radiographic outcome improvements vs placebo in clinically relevant subjects with moderate to severe knee osteoarthritis (OA). This study's objective was to identify effective LOR doses.OBJECTIVELorecivivint (LOR; SM04690), an investigational Wnt pathway modulator, previously demonstrated patient-reported and radiographic outcome improvements vs placebo in clinically relevant subjects with moderate to severe knee osteoarthritis (OA). This study's objective was to identify effective LOR doses.Subjects in this 24-week, Phase 2b, multicenter, randomized, double-blind, placebo (PBO)-controlled trial received an intra-articular injection of 2 mL LOR (0.03, 0.07, 0.15, or 0.23 mg), PBO, or dry-needle sham. The primary efficacy endpoints were changes in Pain NRS [0-10], WOMAC Pain [0-100], WOMAC Function [0-100], and radiographic mJSW outcomes, which were measured using baseline-adjusted analysis of covariance at Week 24. Multiple Comparison Procedure-Modeling (MCP-Mod) was performed for dose modeling.DESIGNSubjects in this 24-week, Phase 2b, multicenter, randomized, double-blind, placebo (PBO)-controlled trial received an intra-articular injection of 2 mL LOR (0.03, 0.07, 0.15, or 0.23 mg), PBO, or dry-needle sham. The primary efficacy endpoints were changes in Pain NRS [0-10], WOMAC Pain [0-100], WOMAC Function [0-100], and radiographic mJSW outcomes, which were measured using baseline-adjusted analysis of covariance at Week 24. Multiple Comparison Procedure-Modeling (MCP-Mod) was performed for dose modeling.In total, 695/700 subjects were treated. Pain NRS showed significant improvements vs PBO after treatment with 0.07 mg and 0.23 mg LOR at Weeks 12 (-0.96, 95% CI [-1.54, -0.37], P = 0.001; -0.78 [-1.39, -0.17], P = 0.012) and 24 (-0.70 [-1.34, -0.06], P = 0.031; -0.82 [-1.51, -0.12], P = 0.022). Additionally, 0.07 mg LOR significantly improved WOMAC Pain and Function subscores vs PBO at Week 12 (P = 0.04, P = 0.021), and 0.23 mg LOR significantly improved both WOMAC subscores at Week 24 (P = 0.031, P = 0.017). No significant differences from PBO were observed for other doses. No radiographic progression was observed in any group at Week 24. MCP-Mod identified 0.07 mg LOR as the lowest effective dose.RESULTSIn total, 695/700 subjects were treated. Pain NRS showed significant improvements vs PBO after treatment with 0.07 mg and 0.23 mg LOR at Weeks 12 (-0.96, 95% CI [-1.54, -0.37], P = 0.001; -0.78 [-1.39, -0.17], P = 0.012) and 24 (-0.70 [-1.34, -0.06], P = 0.031; -0.82 [-1.51, -0.12], P = 0.022). Additionally, 0.07 mg LOR significantly improved WOMAC Pain and Function subscores vs PBO at Week 12 (P = 0.04, P = 0.021), and 0.23 mg LOR significantly improved both WOMAC subscores at Week 24 (P = 0.031, P = 0.017). No significant differences from PBO were observed for other doses. No radiographic progression was observed in any group at Week 24. MCP-Mod identified 0.07 mg LOR as the lowest effective dose.This 24-week Phase 2b trial demonstrated the efficacy of LOR on PROs in knee OA subjects. The optimal dose for future studies was identified as 0.07 mg LOR.CONCLUSIONThis 24-week Phase 2b trial demonstrated the efficacy of LOR on PROs in knee OA subjects. The optimal dose for future studies was identified as 0.07 mg LOR. Lorecivivint (LOR; SM04690), an investigational Wnt pathway modulator, previously demonstrated patient-reported and radiographic outcome improvements vs placebo in clinically relevant subjects with moderate to severe knee osteoarthritis (OA). This study's objective was to identify effective LOR doses. Subjects in this 24-week, Phase 2b, multicenter, randomized, double-blind, placebo (PBO)-controlled trial received an intra-articular injection of 2 mL LOR (0.03, 0.07, 0.15, or 0.23 mg), PBO, or dry-needle sham. The primary efficacy endpoints were changes in Pain NRS [0-10], WOMAC Pain [0-100], WOMAC Function [0-100], and radiographic mJSW outcomes, which were measured using baseline-adjusted analysis of covariance at Week 24. Multiple Comparison Procedure-Modeling (MCP-Mod) was performed for dose modeling. In total, 695/700 subjects were treated. Pain NRS showed significant improvements vs PBO after treatment with 0.07 mg and 0.23 mg LOR at Weeks 12 (-0.96, 95% CI [-1.54, -0.37], P = 0.001; -0.78 [-1.39, -0.17], P = 0.012) and 24 (-0.70 [-1.34, -0.06], P = 0.031; -0.82 [-1.51, -0.12], P = 0.022). Additionally, 0.07 mg LOR significantly improved WOMAC Pain and Function subscores vs PBO at Week 12 (P = 0.04, P = 0.021), and 0.23 mg LOR significantly improved both WOMAC subscores at Week 24 (P = 0.031, P = 0.017). No significant differences from PBO were observed for other doses. No radiographic progression was observed in any group at Week 24. MCP-Mod identified 0.07 mg LOR as the lowest effective dose. This 24-week Phase 2b trial demonstrated the efficacy of LOR on PROs in knee OA subjects. The optimal dose for future studies was identified as 0.07 mg LOR. |
| Author | DiFrancesco, A. Simsek, I. Ghandehari, H. Skrepnik, N. Lane, N.E. Hochberg, M.C. Tambiah, J.R.S. Lattermann, C. McAlindon, T.E. Gibbs, J. Swearingen, C.J. Yazici, Y. Gibofsky, A. |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33588087$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1080/03610920802382619 10.3899/jrheum.100594 10.1002/art.40840 10.1002/art.34453 10.1002/art.41142 10.7326/M19-0675 10.1016/j.joca.2014.10.010 10.1002/art.41315 10.1016/j.joca.2019.05.006 10.1002/art.20726 10.1136/annrheumdis-2016-209252 10.1089/107632704323061753 10.1001/jama.2019.14735 10.12688/f1000research.20575.1 10.1136/ard.2004.023028 10.1016/j.joca.2015.03.005 10.3899/jrheum.110392 10.1093/rheumatology/ket291 10.1016/j.ejpb.2009.06.009 10.1136/bmj.b2844 10.1016/j.joca.2019.06.011 10.1359/jbmr.080901 10.1002/art.1780290816 10.1302/2046-3758.711.BJR-2018-0057.R1 10.1016/j.semarthrit.2016.04.003 10.1038/nrrheum.2013.25 10.1136/annrheumdis-2013-204763 10.1007/s11926-017-0679-z 10.1016/S0140-6736(17)31744-0 10.1002/sim.6991 10.1002/art.23137 10.1111/j.1541-0420.2005.00344.x 10.1136/annrheumdis-2014-206914 10.1016/j.bbrc.2005.06.041 |
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| References | Hochberg, Guermazi, Guehring, Aydemir, Wax, Fleuranceau-Morel (bib17) 2019; 322 Felson, Goggins, Niu, Zhang, Hunter (bib39) 2004 Suri, Morgenroth, Hunter (bib40) 2012; 4 Deshmukh, O’Green, Bossard, Seo, Lamangan, Ibanez (bib19) 2019; 27 Strand, Boers, Idzerda, Kirwan, Kvien, Tugwell (bib29) 2011 McAlindon, Driban, Henrotin, Hunter, Jiang, Skou (bib38) 2015 bib34 Thysen, Luyten, Lories (bib23) 2015 Conaghan, Bowes, Kingsbury, Brett, Guillard, Rizoska (bib7) 2020; 172 Lories, Peeters, Bakker, Tylzanowski, Derese, Schrooten (bib24) 2007 Kraus, Collins, Hargrove, Losina, Nevitt, Katz (bib13) 2017; 76 Lories, Corr, Lane (bib20) 2013; 9 de Boer, Wang, van Blitterswijk (bib21) 2004 (bib32) 1998 Bannuru, Schmid, Kent, Vaysbrot, Wong, McAlindon (bib9) 2015 Schorning, Bornkamp, Bretz, Dette (bib36) 2016; 35 Riddle, Stratford (bib37) 2013 Clauw DJ, Hassett AL. The role of centralised pain in osteoarthritis. Clin Exp Rheumatol. 35 Suppl 107(5):79-84. (bib35) 2013 Barroga, Hu, Deshmukh, Hood (bib41) 2015; 67 Neogi, Felson, Niu, Nevitt, Lewis, Aliabadi (bib14) 2009; 339 Yano, Kugimiya, Ohba, Ikeda, Chikuda, Ogasawara (bib22) 2005 Yazici, McAlindon, Gibofsky, Lane, Clauw, Jones (bib26) 2020 Oct; 72 Lin, Distler, Beyer, Philipi-Schöbinger, Breda, Dees (bib3) 2016 Zhou, Wang, Hamilton, Chen (bib4) 2017 Mobasheri, Saarakkala, Finnilä, Karsdal, Bay-Jensen, van Spil (bib12) 2019; 8 Zhang, Li, Zeng, Lin, Huang, Huang (bib2) 2018 Zhu, Tang, Wu, Hao, Chen, Xie (bib25) 2009 Butoescu, Jordan, Doelker (bib42) 2009 Altman, Asch, Bloch, Bole, Borenstein, Brandt (bib27) 1986; 29 Fleischmann, Bliddal, Blanco, Schnitzer, Peterfy, Chen (bib8) 2019; 71 Ting (bib31) 2009; 38 Loeser, Goldring, Scanzello, Goldring (bib18) 2012 Cross, Smith, Hoy, Nolte, Ackerman, Fransen (bib1) 2014; 73 Roberts, Nunes, Buckner, Latchem, Constanti, Miller (bib10) 2016 Bretz, Pinheiro, Branson (bib33) 2005; 61 Wolfe, Clauw, Fitzcharles, Goldenberg, Häuser, Katz (bib28) 2011; 38 Altman, Devji, Bhandari, Fierlinger, Niazi, Christensen (bib16) 2016; 46 Kolasinski, Neogi, Hochberg, Oatis, Guyatt, Block (bib6) 2020; 72 Tubach, Ravaud, Baron, Falissard, Logeart, Bellamy (bib30) 2005; 64 Bannuru, Osani, Vaysbrot, Arden, Bennell, Bierma-Zeinstra (bib5) 2019; 27 da Costa, Reichenbach, Keller, Nartey, Wandel, Jüni (bib11) 2017 Lin (10.1016/j.joca.2021.02.004_bib3) 2016 Bannuru (10.1016/j.joca.2021.02.004_bib9) 2015 Ting (10.1016/j.joca.2021.02.004_bib31) 2009; 38 de Boer (10.1016/j.joca.2021.02.004_bib21) 2004 Zhu (10.1016/j.joca.2021.02.004_bib25) 2009 Altman (10.1016/j.joca.2021.02.004_bib27) 1986; 29 10.1016/j.joca.2021.02.004_bib15 Wolfe (10.1016/j.joca.2021.02.004_bib28) 2011; 38 Fleischmann (10.1016/j.joca.2021.02.004_bib8) 2019; 71 Kolasinski (10.1016/j.joca.2021.02.004_bib6) 2020; 72 Yazici (10.1016/j.joca.2021.02.004_bib26) 2020; 72 Thysen (10.1016/j.joca.2021.02.004_bib23) 2015 Yano (10.1016/j.joca.2021.02.004_bib22) 2005 McAlindon (10.1016/j.joca.2021.02.004_bib38) 2015 (10.1016/j.joca.2021.02.004_bib32) 1998 Strand (10.1016/j.joca.2021.02.004_bib29) 2011 Cross (10.1016/j.joca.2021.02.004_bib1) 2014; 73 Loeser (10.1016/j.joca.2021.02.004_bib18) 2012 Conaghan (10.1016/j.joca.2021.02.004_bib7) 2020; 172 Roberts (10.1016/j.joca.2021.02.004_bib10) 2016 Zhang (10.1016/j.joca.2021.02.004_bib2) 2018 Lories (10.1016/j.joca.2021.02.004_bib20) 2013; 9 Bretz (10.1016/j.joca.2021.02.004_bib33) 2005; 61 Hochberg (10.1016/j.joca.2021.02.004_bib17) 2019; 322 (10.1016/j.joca.2021.02.004_bib35) 2013 da Costa (10.1016/j.joca.2021.02.004_bib11) 2017 Schorning (10.1016/j.joca.2021.02.004_bib36) 2016; 35 Tubach (10.1016/j.joca.2021.02.004_bib30) 2005; 64 Suri (10.1016/j.joca.2021.02.004_bib40) 2012; 4 Barroga (10.1016/j.joca.2021.02.004_bib41) 2015; 67 Lories (10.1016/j.joca.2021.02.004_bib24) 2007 Felson (10.1016/j.joca.2021.02.004_bib39) 2004 Butoescu (10.1016/j.joca.2021.02.004_bib42) 2009 Kraus (10.1016/j.joca.2021.02.004_bib13) 2017; 76 Bannuru (10.1016/j.joca.2021.02.004_bib5) 2019; 27 Riddle (10.1016/j.joca.2021.02.004_bib37) 2013 Mobasheri (10.1016/j.joca.2021.02.004_bib12) 2019; 8 Zhou (10.1016/j.joca.2021.02.004_bib4) 2017 Neogi (10.1016/j.joca.2021.02.004_bib14) 2009; 339 Altman (10.1016/j.joca.2021.02.004_bib16) 2016; 46 Deshmukh (10.1016/j.joca.2021.02.004_bib19) 2019; 27 |
| References_xml | – volume: 61 start-page: 738 year: 2005 end-page: 748 ident: bib33 article-title: Combining multiple comparisons and modeling techniques in dose-response studies publication-title: Biometrics – volume: 71 start-page: 1056 year: 2019 end-page: 1069 ident: bib8 article-title: A phase II trial of lutikizumab, an anti–interleukin-1α/β dual variable domain immunoglobulin, in knee osteoarthritis patients with synovitis publication-title: Arthritis Rheumatol – volume: 9 start-page: 328 year: 2013 end-page: 339 ident: bib20 article-title: To Wnt or not to Wnt: the bone and joint health dilemma publication-title: Nat Rev Rheumatol – year: 2016 ident: bib3 article-title: Inhibition of Notch1 promotes hedgehog signalling in a HES1-dependent manner in chondrocytes and exacerbates experimental osteoarthritis publication-title: Ann Rheum Dis – volume: 8 year: 2019 ident: bib12 article-title: Recent advances in understanding the phenotypes of osteoarthritis publication-title: F1000Research – year: 2005 ident: bib22 article-title: The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner publication-title: Biochem Biophys Res Commun – year: 1998 ident: bib32 article-title: Note for guidance on statistical principles for clinical trials publication-title: ICH Topic E9: Statistical Principles for Clinical Trials – volume: 73 start-page: 1323 year: 2014 end-page: 1330 ident: bib1 article-title: The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 study publication-title: Ann Rheum Dis – year: 2018 ident: bib2 article-title: Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-β1) publication-title: Bone Joint Res – volume: 76 start-page: 186 year: 2017 end-page: 195 ident: bib13 article-title: Predictive validity of biochemical biomarkers in knee osteoarthritis: data from the FNIH OA Biomarkers Consortium publication-title: Ann Rheum Dis – year: 2004 ident: bib39 article-title: The effect of body weight on progression of knee osteoarthritis is dependent on alignment publication-title: Arthritis Rheum – year: 2012 ident: bib18 article-title: Osteoarthritis: a disease of the joint as an organ publication-title: Arthritis Rheum – volume: 72 start-page: 220 year: 2020 end-page: 233 ident: bib6 article-title: 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee publication-title: Arthritis Rheumatol – year: 2004 ident: bib21 article-title: Effects of wnt signaling on proliferation and differentiation of human mesenchymal stem cells publication-title: Tissue Eng – reference: Clauw DJ, Hassett AL. The role of centralised pain in osteoarthritis. Clin Exp Rheumatol. 35 Suppl 107(5):79-84. – ident: bib34 article-title: Drug development tools: fit-for-purpose initiative – volume: 64 start-page: 34 year: 2005 end-page: 37 ident: bib30 article-title: Evaluation of clinically relevant states in patient reported outcomes in knee and hip osteoarthritis: the patient acceptable symptom state publication-title: Ann Rheum Dis – year: 2016 ident: bib10 article-title: Paracetamol: not as safe as we thought? A systematic literature review of observational studies publication-title: Ann Rheum Dis – year: 2009 ident: bib25 article-title: Activation of β-catenin signaling in articular chondrocytes leads to osteoarthritis-like phenotype in adult β-catenin conditional activation mice publication-title: J Bone Miner Res – year: 2017 ident: bib4 article-title: Wnt/β-catenin signaling in osteoarthritis and in other forms of arthritis publication-title: Curr Rheumatol Rep – volume: 172 start-page: 86 year: 2020 end-page: 95 ident: bib7 article-title: Disease-modifying effects of a novel cathepsin k inhibitor in osteoarthritis: a randomized controlled trial publication-title: Ann Intern Med – volume: 35 start-page: 4021 year: 2016 end-page: 4040 ident: bib36 article-title: Model selection versus model averaging in dose finding studies publication-title: Stat Med – year: 2009 ident: bib42 article-title: Intra-articular drug delivery systems for the treatment of rheumatic diseases: a review of the factors influencing their performance publication-title: Eur J Pharm Biopharm – year: 2015 ident: bib9 article-title: Comparative effectiveness of pharmacologic interventions for knee osteoarthritis publication-title: Ann Intern Med – volume: 46 start-page: 151 year: 2016 end-page: 159 ident: bib16 article-title: Clinical benefit of intra-articular saline as a comparator in clinical trials of knee osteoarthritis treatments: a systematic review and meta-analysis of randomized trials publication-title: Semin Arthritis Rheum – volume: 72 start-page: 1694 year: 2020 Oct end-page: 1706 ident: bib26 article-title: Lorecivivint, a novel intra-articular CLK2/DYRK1A inhibitor and wnt pathway modulator for treatment of knee osteoarthritis: a phase 2 randomized trial publication-title: Arthritis Rheum – volume: 27 start-page: 1347 year: 2019 end-page: 1360 ident: bib19 article-title: Modulation of the Wnt pathway through inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying approach for knee osteoarthritis treatment publication-title: Osteoarthr Cartil – year: 2013 ident: bib35 article-title: Committee for Medicinal Products for Human Use (CHMP) Qualification Opinion of MCP-Mod as an Efficient Statistical Methodology for Model-Based Design and Analysis of Phase II Dose Finding Studies under Model Uncertainty – volume: 38 start-page: 1113 year: 2011 end-page: 1122 ident: bib28 article-title: Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR preliminary diagnostic criteria for fibromyalgia publication-title: J Rheumatol – volume: 38 start-page: 3282 year: 2009 end-page: 3296 ident: bib31 article-title: Practical and statistical considerations in designing an early phase II osteoarthritis clinical trial: a case study publication-title: Commun Stat Theor Methods – volume: 27 start-page: 1578 year: 2019 end-page: 1589 ident: bib5 article-title: OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis publication-title: Osteoarthr Cartil – volume: 67 year: 2015 ident: bib41 article-title: Discovery of an intra-articular injection small molecule inhibitor of the wnt pathway (SM04690) as a potential disease modifying treatment for knee osteoarthritis publication-title: Arthritis Rheumatol – year: 2011 ident: bib29 article-title: It’s good to feel better but it’s better to feel good and even better to feel good as soon as possible for as long as possible. Response criteria and the importance of change at OMERACT 10 publication-title: J Rheumatol – year: 2017 ident: bib11 article-title: Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis publication-title: Lancet – volume: 322 start-page: 1360 year: 2019 end-page: 1370 ident: bib17 article-title: Effect of intra-articular sprifermin vs placebo on femorotibial joint cartilage thickness in patients with osteoarthritis: the FORWARD randomized clinical trial publication-title: JAMA - J Am Med Assoc – volume: 29 start-page: 1039 year: 1986 end-page: 1049 ident: bib27 article-title: Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee publication-title: Arthritis Rheum – start-page: 2229 year: 2013 end-page: 2237 ident: bib37 article-title: Unilateral vs bilateral symptomatic knee osteoarthritis: associations between pain intensity and function publication-title: Rheumatology – volume: 4 start-page: S10 year: 2012 end-page: S19 ident: bib40 article-title: Epidemiology of osteoarthritis and associated comorbidities publication-title: PMRJ – volume: 339 year: 2009 ident: bib14 article-title: Association between radiographic features of knee osteoarthritis and pain: results from two cohort studies publication-title: BMJ – year: 2015 ident: bib23 article-title: Loss of Frzb and Sfrp1 differentially affects joint homeostasis in instability-induced osteoarthritis publication-title: Osteoarthr Cartil – year: 2007 ident: bib24 article-title: Articular cartilage and biomechanical properties of the long bones in Frzb-knockout mice publication-title: Arthritis Rheum – year: 2015 ident: bib38 article-title: OARSI Clinical Trials Recommendations: design, conduct, and reporting of clinical trials for knee osteoarthritis publication-title: Osteoarthr Cartil – volume: 38 start-page: 3282 issue: 18 year: 2009 ident: 10.1016/j.joca.2021.02.004_bib31 article-title: Practical and statistical considerations in designing an early phase II osteoarthritis clinical trial: a case study publication-title: Commun Stat Theor Methods doi: 10.1080/03610920802382619 – volume: 38 start-page: 1113 issue: 6 year: 2011 ident: 10.1016/j.joca.2021.02.004_bib28 article-title: Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR preliminary diagnostic criteria for fibromyalgia publication-title: J Rheumatol doi: 10.3899/jrheum.100594 – volume: 71 start-page: 1056 issue: 7 year: 2019 ident: 10.1016/j.joca.2021.02.004_bib8 article-title: A phase II trial of lutikizumab, an anti–interleukin-1α/β dual variable domain immunoglobulin, in knee osteoarthritis patients with synovitis publication-title: Arthritis Rheumatol doi: 10.1002/art.40840 – year: 2016 ident: 10.1016/j.joca.2021.02.004_bib3 article-title: Inhibition of Notch1 promotes hedgehog signalling in a HES1-dependent manner in chondrocytes and exacerbates experimental osteoarthritis publication-title: Ann Rheum Dis – year: 2012 ident: 10.1016/j.joca.2021.02.004_bib18 article-title: Osteoarthritis: a disease of the joint as an organ publication-title: Arthritis Rheum doi: 10.1002/art.34453 – volume: 72 start-page: 220 issue: 2 year: 2020 ident: 10.1016/j.joca.2021.02.004_bib6 article-title: 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee publication-title: Arthritis Rheumatol doi: 10.1002/art.41142 – volume: 172 start-page: 86 issue: 2 year: 2020 ident: 10.1016/j.joca.2021.02.004_bib7 article-title: Disease-modifying effects of a novel cathepsin k inhibitor in osteoarthritis: a randomized controlled trial publication-title: Ann Intern Med doi: 10.7326/M19-0675 – year: 1998 ident: 10.1016/j.joca.2021.02.004_bib32 article-title: Note for guidance on statistical principles for clinical trials – year: 2015 ident: 10.1016/j.joca.2021.02.004_bib23 article-title: Loss of Frzb and Sfrp1 differentially affects joint homeostasis in instability-induced osteoarthritis publication-title: Osteoarthr Cartil doi: 10.1016/j.joca.2014.10.010 – volume: 72 start-page: 1694 issue: 10 year: 2020 ident: 10.1016/j.joca.2021.02.004_bib26 article-title: Lorecivivint, a novel intra-articular CLK2/DYRK1A inhibitor and wnt pathway modulator for treatment of knee osteoarthritis: a phase 2 randomized trial publication-title: Arthritis Rheum doi: 10.1002/art.41315 – volume: 27 start-page: 1347 year: 2019 ident: 10.1016/j.joca.2021.02.004_bib19 article-title: Modulation of the Wnt pathway through inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying approach for knee osteoarthritis treatment publication-title: Osteoarthr Cartil doi: 10.1016/j.joca.2019.05.006 – year: 2004 ident: 10.1016/j.joca.2021.02.004_bib39 article-title: The effect of body weight on progression of knee osteoarthritis is dependent on alignment publication-title: Arthritis Rheum doi: 10.1002/art.20726 – volume: 4 start-page: S10 issue: 5 year: 2012 ident: 10.1016/j.joca.2021.02.004_bib40 article-title: Epidemiology of osteoarthritis and associated comorbidities publication-title: PMRJ – volume: 76 start-page: 186 issue: 1 year: 2017 ident: 10.1016/j.joca.2021.02.004_bib13 article-title: Predictive validity of biochemical biomarkers in knee osteoarthritis: data from the FNIH OA Biomarkers Consortium publication-title: Ann Rheum Dis doi: 10.1136/annrheumdis-2016-209252 – year: 2004 ident: 10.1016/j.joca.2021.02.004_bib21 article-title: Effects of wnt signaling on proliferation and differentiation of human mesenchymal stem cells publication-title: Tissue Eng doi: 10.1089/107632704323061753 – volume: 322 start-page: 1360 issue: 14 year: 2019 ident: 10.1016/j.joca.2021.02.004_bib17 article-title: Effect of intra-articular sprifermin vs placebo on femorotibial joint cartilage thickness in patients with osteoarthritis: the FORWARD randomized clinical trial publication-title: JAMA - J Am Med Assoc doi: 10.1001/jama.2019.14735 – volume: 8 year: 2019 ident: 10.1016/j.joca.2021.02.004_bib12 article-title: Recent advances in understanding the phenotypes of osteoarthritis publication-title: F1000Research doi: 10.12688/f1000research.20575.1 – volume: 64 start-page: 34 issue: 1 year: 2005 ident: 10.1016/j.joca.2021.02.004_bib30 article-title: Evaluation of clinically relevant states in patient reported outcomes in knee and hip osteoarthritis: the patient acceptable symptom state publication-title: Ann Rheum Dis doi: 10.1136/ard.2004.023028 – year: 2015 ident: 10.1016/j.joca.2021.02.004_bib38 article-title: OARSI Clinical Trials Recommendations: design, conduct, and reporting of clinical trials for knee osteoarthritis publication-title: Osteoarthr Cartil doi: 10.1016/j.joca.2015.03.005 – year: 2011 ident: 10.1016/j.joca.2021.02.004_bib29 article-title: It’s good to feel better but it’s better to feel good and even better to feel good as soon as possible for as long as possible. Response criteria and the importance of change at OMERACT 10 publication-title: J Rheumatol doi: 10.3899/jrheum.110392 – start-page: 2229 issue: September year: 2013 ident: 10.1016/j.joca.2021.02.004_bib37 article-title: Unilateral vs bilateral symptomatic knee osteoarthritis: associations between pain intensity and function publication-title: Rheumatology doi: 10.1093/rheumatology/ket291 – year: 2009 ident: 10.1016/j.joca.2021.02.004_bib42 article-title: Intra-articular drug delivery systems for the treatment of rheumatic diseases: a review of the factors influencing their performance publication-title: Eur J Pharm Biopharm doi: 10.1016/j.ejpb.2009.06.009 – volume: 339 year: 2009 ident: 10.1016/j.joca.2021.02.004_bib14 article-title: Association between radiographic features of knee osteoarthritis and pain: results from two cohort studies publication-title: BMJ doi: 10.1136/bmj.b2844 – volume: 27 start-page: 1578 issue: 11 year: 2019 ident: 10.1016/j.joca.2021.02.004_bib5 article-title: OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis publication-title: Osteoarthr Cartil doi: 10.1016/j.joca.2019.06.011 – year: 2009 ident: 10.1016/j.joca.2021.02.004_bib25 article-title: Activation of β-catenin signaling in articular chondrocytes leads to osteoarthritis-like phenotype in adult β-catenin conditional activation mice publication-title: J Bone Miner Res doi: 10.1359/jbmr.080901 – volume: 29 start-page: 1039 issue: 8 year: 1986 ident: 10.1016/j.joca.2021.02.004_bib27 article-title: Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee publication-title: Arthritis Rheum doi: 10.1002/art.1780290816 – year: 2018 ident: 10.1016/j.joca.2021.02.004_bib2 article-title: Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-β1) publication-title: Bone Joint Res doi: 10.1302/2046-3758.711.BJR-2018-0057.R1 – ident: 10.1016/j.joca.2021.02.004_bib15 – volume: 46 start-page: 151 issue: 2 year: 2016 ident: 10.1016/j.joca.2021.02.004_bib16 article-title: Clinical benefit of intra-articular saline as a comparator in clinical trials of knee osteoarthritis treatments: a systematic review and meta-analysis of randomized trials publication-title: Semin Arthritis Rheum doi: 10.1016/j.semarthrit.2016.04.003 – volume: 9 start-page: 328 issue: 6 year: 2013 ident: 10.1016/j.joca.2021.02.004_bib20 article-title: To Wnt or not to Wnt: the bone and joint health dilemma publication-title: Nat Rev Rheumatol doi: 10.1038/nrrheum.2013.25 – year: 2015 ident: 10.1016/j.joca.2021.02.004_bib9 article-title: Comparative effectiveness of pharmacologic interventions for knee osteoarthritis publication-title: Ann Intern Med – volume: 73 start-page: 1323 issue: 7 year: 2014 ident: 10.1016/j.joca.2021.02.004_bib1 article-title: The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 study publication-title: Ann Rheum Dis doi: 10.1136/annrheumdis-2013-204763 – volume: 67 issue: suppl 10 year: 2015 ident: 10.1016/j.joca.2021.02.004_bib41 article-title: Discovery of an intra-articular injection small molecule inhibitor of the wnt pathway (SM04690) as a potential disease modifying treatment for knee osteoarthritis publication-title: Arthritis Rheumatol – year: 2017 ident: 10.1016/j.joca.2021.02.004_bib4 article-title: Wnt/β-catenin signaling in osteoarthritis and in other forms of arthritis publication-title: Curr Rheumatol Rep doi: 10.1007/s11926-017-0679-z – year: 2017 ident: 10.1016/j.joca.2021.02.004_bib11 article-title: Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis publication-title: Lancet doi: 10.1016/S0140-6736(17)31744-0 – year: 2013 ident: 10.1016/j.joca.2021.02.004_bib35 – volume: 35 start-page: 4021 issue: 22 year: 2016 ident: 10.1016/j.joca.2021.02.004_bib36 article-title: Model selection versus model averaging in dose finding studies publication-title: Stat Med doi: 10.1002/sim.6991 – year: 2007 ident: 10.1016/j.joca.2021.02.004_bib24 article-title: Articular cartilage and biomechanical properties of the long bones in Frzb-knockout mice publication-title: Arthritis Rheum doi: 10.1002/art.23137 – volume: 61 start-page: 738 issue: 3 year: 2005 ident: 10.1016/j.joca.2021.02.004_bib33 article-title: Combining multiple comparisons and modeling techniques in dose-response studies publication-title: Biometrics doi: 10.1111/j.1541-0420.2005.00344.x – year: 2016 ident: 10.1016/j.joca.2021.02.004_bib10 article-title: Paracetamol: not as safe as we thought? 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