HUMAN FGF 4 GENE TRANSFER IN PATIENTS W/ ANGINA

这是一项I/II期临床试验。本研究的目的是观察腺病毒介导的人成纤维细胞生长因子-4基因转移治疗稳定性劳力型心绞痛(II级和III级)的安全性和抗缺血效果，以便为后续研究选择潜在的安全有效剂量。这是一项双盲、剂量递增、安慰剂对照研究。每个剂量组由至少9名活动患者和3名安慰剂患者组成。首先将研究最低剂量(3.2×10^9病毒颗粒)。对于每个剂量组，回顾前两周的安全性观察，并确认第一个患者随机接受有效药物治疗后，第二个患者随机接受有效药物治疗的安全性。在给每个剂量组中的其余患者给药之前，对第二个患者后两周的安全性观察进行回顾并确认其安全性。所有患者的赞助者都被允许解盲，但患者、研究人员和他的工作人员在整个研究过程中都保持失明。核心实验室以盲法读取运动心电图、负荷超声心动图和冠状动脉造影术。在约翰霍普金斯大学登记的任何受试者中都没有出现不良事件。在全国范围内，一名患者的肝酶有一过性升高，没有后遗症。由于研究仍在进行中，目前还没有疗效数据。使用基因疗法进行血管生成的其他研究显示，在血管生长领域取得了显著成果。然而，这一领域的研究仍处于非常早期的阶段。

This is a Phase I/II clinical trial. The objective of this study is to evaluate the safety and anti-ischemic effects of adenovirus mediated hFGF-4 gene transfer in patients with stable exertional angina (Class II and Class III) so that a potentially safe and effective dose may be selected for a subsequent study. This is a double-blind, ascending dose, placebo controlled study. Each dose group consists of at least nine active and three placebo patients. The lowest dose (3.2 x 10^9 viral particles) will be studied first. For each dose group, safety observations during the first two weeks are reviewed and safety confirmed for the first patient randomized to active medication before dosing the second patient randomized to active medication. Safety observations for two weeks after the second patient are reviewed and safety confirmed before dosing the remaining patients in each dose group. Sponsor unblinding for all patients is allowed, but the patient, investigator, and his staff all remain blinded throughout the study. Core laboratories read, in a blinded fashion, exercise ECGs, stress echocardiograms, and coronary angiography. There have been no adverse events in any of the subjects enrolled at Johns Hopkins. Nationally, one patient had a transient rise in liver enzymes with no sequelae. As the study is still in progress, efficacy data is not yet available. Other research into the use of gene therapy for angiogenesis has shown remarkable results in the area of blood vessel growth. However, this area of study is still in the very early stages.