注射用截短型人成纤维细胞生长因子18治疗膝骨关节炎的Ⅰ期临床试验OA

AIM To evaluate the efficacy and safety of injectable truncated human fibroblast growth factor 18(K11 for injection)in the treatment of knee osteoarthritis(KOA).METHODS From October 2022 to November 2023,36 patients with symptomatic KOA of Kellgren-Lawrence grade Ⅱ or Ⅲ,who did not require knee surgery within 6 months,were enrolled from 4 hospitals.They were randomly assigned in a 5∶1 ratio to the treatment group(n=30)or the control group(n=6).The treatment group was further randomly divided into 3 dose subgroups of 30,100,and 200 μg,with 10 participants in each subgroup.The treatment group received injectable K11,while the control group received placebo.All patients received intra-articular injection once a week for 3 weeks as one administration cycle,with 3 months as one treatment course,and a total of 2 treatment courses.Efficacy was evaluated by changes from baseline in visual analog scale(VAS)scores for target knee pain/swelling,as well as WOMAC pain,stiffness,physical function scores,and total score at baseline,at week 13,and at week 26.Safety was assessed by adverse reactions and laboratory abnormalities during the trial.RESULTS During the trial,4 subjects in the 100 μg subgroup withdrew,while the remaining 32 subjects completed the trial.At week 26,VAS scores for target knee pain showed a decreasing trend,with greater changes from baseline in all dose groups than in the control group.VAS scores for swelling also decreased,and only the 200 μg group showed a greater change from baseline than the control group.WOMAC pain,stiffness,physical function scores and total score tended to decrease.Compared with the control group,changes from baseline in WOMAC pain scores and total scores were greater in all K11 dose groups,while changes in WOMAC stiffness and physical function scores were similar to those in the control group.The most common adverse reactions in each dose group were joint pain,joint stiffness,and joint swelling,with no acute inflammatory reactions observed.CONCLUSION Multiple intra-articular injections of K11 for the treatment of KOA demonstrate a favorable safety profile and preliminary efficacy,showing good application prospects.