Karsdal M A, Byrjalsen I, Alexandersen P, Bihlet A, Andersen J R, Riis B J, Bay-Jensen A C, Christiansen C
Nordic Bioscience, DK-2730 Herlev, Denmark.
Nordic Bioscience, DK-2730 Herlev, Denmark.
Osteoarthritis Cartilage. 2015 Apr;23(4):532-43. doi: 10.1016/j.joca.2014.12.019. Epub 2015 Jan 9.
To evaluate the structure-modifying and symptom efficacy, as well as safety and tolerability of oral salmon calcitonin (sCT) formulated with a 5-CNAC carrier (a molecule based on Eligen(®) technology), in osteoarthritis (OA) patients with moderate to severe knee pain and joint structural damage classified as Kellgren and Lawrence (KL)2-3.
This is the combined reporting of two randomized, double-blind, multi-center, placebo-controlled trials (CSMC021C2301 and CSMC021C2302), evaluating the efficacy and safety of oral sCT in patients with painful knee OA with structural manifestations, enrolling 1176 and 1030 patients, respectively. Study subjects were randomized (1:1) to oral sCT 0.8 mg twice daily or placebo (PBO) for 24 months. The primary efficacy objectives were to examine the treatment effect compared to placebo on change over 24 months in joint space width (JSW) in the signal knee measured by X-ray, and to examine the change in pain and function using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) questionnaire. Other study parameters included patient and physician global assessment, and biochemical markers of bone (CTX-I) and cartilage degradation (CTX-II).
At the 24 month endpoint there was no statistically significant treatment effect on joint space narrowing (JSN) in any of the two studies. In CSMC021C2301 there was a treatment effect on WOMAC (sum of pain, function, stiffness, and total scores) as well as on the biomarkers of bone and joint metabolism, but due to the hierarchical testing procedure the treatment effect was not claimed statistically significant.
The present formulation of oral sCT did not provide reproducible clinical benefits in patients with symptomatic knee OA (NCT00486434, NCT00704847).
评估用5-CNAC载体（一种基于Eligen®技术的分子）配制的口服鲑鱼降钙素（sCT）对中度至重度膝关节疼痛且关节结构损伤分类为凯尔格伦和劳伦斯（KL）2 - 3级的骨关节炎（OA）患者的结构改善和症状疗效，以及安全性和耐受性。
这是两项随机、双盲、多中心、安慰剂对照试验（CSMC021C2301和CSMC021C2302）的联合报告，评估口服sCT对有结构表现的疼痛性膝关节OA患者的疗效和安全性，分别纳入1176例和1030例患者。研究对象被随机（1:1）分为每日两次口服0.8 mg sCT或安慰剂（PBO），为期24个月。主要疗效目标是通过X线测量信号膝关节在24个月内关节间隙宽度（JSW）相对于安慰剂的变化来检查治疗效果，并使用西安大略和麦克马斯特大学骨关节炎（WOMAC）问卷检查疼痛和功能的变化。其他研究参数包括患者和医生的整体评估，以及骨（CTX-I）和软骨降解（CTX-II）的生化标志物。
在24个月终点时，两项研究中的任何一项对关节间隙变窄（JSN）均无统计学上显著的治疗效果。在CSMC021C2301中，对WOMAC（疼痛、功能、僵硬和总分的总和）以及骨和关节代谢的生物标志物有治疗效果，但由于分层检验程序，该治疗效果未被认定具有统计学显著性。
目前的口服sCT制剂对有症状的膝关节OA患者未提供可重复的临床益处（NCT00486434，NCT00704847）。
