目的:Somatrogon是一种长效重组人生长激素(GH),每周一次用于治疗GH缺乏症(GHD)儿童。12个月,每周一次的somatrogon与每天启动一次GH(Genotropin®),之后,参与者可以加入开放标签扩展(OLE),评估长期生长激素治疗的安全性和有效性.
方法:有五个研究阶段,I期和II期均为6个月,而III期,IV,V分别为12个月。在主要研究(I期和II期)中,53名患有GHD的青春期前儿童被随机分为每周一次的somatrogon(0.25、0.48或0.66mg/kg/周)或每天一次的Genotropin(0.034mg/kg/天);48名继续进入OLE,包括III期(原始生长激素剂量;随机分配给三种生长激素剂量之一的Genotropin接受者),IV期(somatrogon0.66mg/kg/周),和第V期(预填充的somatrogon笔[0.66mg/kg/周])。
结果:在III期结束时,0.25、0.48和0.66mg/kg/周组的平均±SD年高度速度(HV)为7.73±1.89,7.54±1.28和8.81±1.12cm/年,分别在IV/V期间维持HV身高SD评分(SDS)在整个OLE中显示出逐步改善,无论初始队列分配如何,在第V年1期结束时接近正常范围(-0.69±SD0.87)。81.3%的参与者报告了轻度或中度治疗引起的不良事件。大多数与研究药物无关。
结论:对于患有GHD的青春期前身材矮小儿童,每周一次的somatrogon长达5年的耐受性良好,并导致身高SDS和delta身高SDS的持续改善。Clinicaltrials.gov:NCT01592500。
OBJECTIVE: Somatrogon is a long-acting recombinant human growth hormone (GH) employed as a once-weekly treatment for children with GH deficiency (GHD). A 12-month, phase 2 study of once-weekly somatrogon vs. once-daily GH (Genotropin®) was initiated, after which participants could enroll into an open-label extension (OLE) evaluating the safety and efficacy of long-term somatrogon treatment.
METHODS: There were five study periods, Periods I and II were 6 months each while Periods III, IV, and V were 12 months each. In the main study (Periods I and II), 53 prepubertal children with GHD were randomized to once-weekly somatrogon (0.25, 0.48, or 0.66 mg/kg/week) or once-daily Genotropin (0.034 mg/kg/day); 48 continued into the OLE, consisting of Period III (original somatrogon dose; Genotropin recipients randomized to one of three somatrogon doses), Period IV (somatrogon 0.66 mg/kg/week), and Period V (prefilled somatrogon pen [0.66 mg/kg/week]).
RESULTS: At the end of Period III, the mean ± SD annual height velocity (HV) for 0.25, 0.48, and 0.66 mg/kg/week somatrogon groups was 7.73 ± 1.89, 7.54 ± 1.28, and 8.81 ± 1.12 cm/year, respectively; HV was sustained during Periods IV/V. Height SD scores (SDS) showed progressive improvement throughout the OLE, regardless of initial cohort assignment, approaching the normal range (-0.69 ± SD 0.87) at the end of Period V Year 1. Mild or moderate treatment-emergent adverse events were reported in 81.3% of participants, most unrelated to study drug.
CONCLUSIONS: Up to 5 years of once-weekly somatrogon was well tolerated and resulted in sustained improvement in height SDS and delta height SDS in prepubertal short children with GHD.