Department of Dermatology and Cutaneous Surgery, University of Miami, Leonard M Miller School of Medicine, Miami, FL, USA.
Lancet. 2012 Sep 15;380(9846):977-85. doi: 10.1016/S0140-6736(12)60644-8. Epub 2012 Aug 3.
Many patients with venous leg ulcers do not heal with standard care. HP802-247 is a novel spray-applied cell therapy containing growth-arrested allogeneic neonatal keratinocytes and fibroblasts. We compared different cell concentrations and dosing frequencies of HP802-247 for benefit and harm when applied to chronic venous leg ulcers.
We enrolled adult outpatients from 28 centres in the USA and Canada with up to three ulcers, venous reflux confirmed by doppler ultrasonography, and adequate arterial flow in this phase 2, double-blind, randomised, placebo-controlled trial if at least one ulcer measured 2-12 cm(2) in area and had persisted for 6-104 weeks. Patients were randomly assigned by computer-generated block randomisation in a 1:1:1:1:1 ratio to 5·0×10(6) cells per mL every 7 days or every 14 days, or 0·5×10(6) cells per mL every 7 days or every 14 days, or to vehicle alone every 7 days. All five groups received four-layer compression bandages. The trial sponsor, trial monitors, statisticians, investigators, centre personnel, and patients were masked to treatment allocation. The primary endpoint was mean percentage change in wound area at the end of 12 weeks. Analyses were by intention to treat, excluding one patient who died of unrelated causes before first treatment. This trial is registered with ClinicalTrials.gov NCT00852995.
45 patients were assigned to 5·0×10(6) cells per mL every 7 days, 44 to 5·0×10(6) cells per mL every 14 days, 43 to 0·5 ×10(6) cells per mL every 7 days, 46 to 0·5 ×10(6) cells per mL every 14 days, and 50 to vehicle alone. All required visits were completed by 205 patients. The primary outcome analysis showed significantly greater mean reduction in wound area associated with active treatment compared with vehicle (p=0·0446), with the dose of 0·5 ×10(6) cells/mL every 14 days showing the largest improvement compared with vehicle (15·98%, 95% CI 5·56-26·41, p=0·0028). Adverse events were much the same across all groups, with only new skin ulcers and cellulitis occurring in more than 5% of patients.
Venous leg ulcers can be healed with a spray formulation of allogeneic neonatal keratinocytes and fibroblasts without the need for tissue engineering, at an optimum dose of 0·5×10(6) cells per mL every 14 days.
Healthpoint Biotherapeutics.
许多静脉性腿部溃疡患者在接受标准治疗后并未痊愈。HP802-247 是一种新型喷雾应用细胞疗法，含有生长停滞的同种异体新生儿角质形成细胞和成纤维细胞。我们比较了不同细胞浓度和 HP802-247 的给药频率，以评估其在慢性静脉性腿部溃疡中的益处和危害。
我们在 28 个美国和加拿大中心招募了成年门诊患者，这些患者的腿部溃疡最多有 3 个，通过多普勒超声检查证实有静脉反流，并且在该 2 期、双盲、随机、安慰剂对照试验中，如果至少一个溃疡的面积为 2-12cm²，且持续时间为 6-104 周，那么动脉血流充足。患者通过计算机生成的块随机化以 1:1:1:1:1 的比例随机分配到 5.0×10⁶个细胞/mL，每 7 天或每 14 天一次，或 0.5×10⁶个细胞/mL，每 7 天或每 14 天一次，或单独使用载体，每 7 天一次。所有 5 组均接受四层压缩绷带。试验赞助商、试验监查员、统计人员、研究者、中心人员和患者均对治疗分配进行了盲法。主要终点是 12 周结束时伤口面积的平均百分比变化。分析采用意向治疗，排除了一名因与治疗无关的原因在首次治疗前死亡的患者。该试验在 ClinicalTrials.gov 注册，编号为 NCT00852995。
45 名患者被分配到 5.0×10⁶个细胞/mL，每 7 天一次，44 名患者分配到 5.0×10⁶个细胞/mL，每 14 天一次，43 名患者分配到 0.5×10⁶个细胞/mL，每 7 天一次，46 名患者分配到 0.5×10⁶个细胞/mL，每 14 天一次，50 名患者分配到单独使用载体。所有需要的就诊都由 205 名患者完成。主要结局分析显示，与载体相比，活性治疗与伤口面积的显著更大的平均减少相关（p=0.0446），与载体相比，剂量为 0.5×10⁶个细胞/mL，每 14 天一次显示出最大的改善（15.98%，95%CI 5.56-26.41，p=0.0028）。所有组的不良反应都差不多，只有新的皮肤溃疡和蜂窝织炎在超过 5%的患者中发生。
静脉性腿部溃疡可以通过使用同种异体新生儿角质形成细胞和成纤维细胞的喷雾制剂来治愈，而无需组织工程，最佳剂量为每 14 天 0.5×10⁶个细胞/mL。
Healthpoint Biotherapeutics。
