238 A randomized, double-blind placebo-controlled study of NV1FGF gene therapy in critical limb ischemia patients (TAMARIS Study): Rationale, design and baseline patient characteristics

Abstract

Patients with critical limb ischemia (CLI) unsuitable for revascularization have a high rate of amputation and mortality (30% and 25% at 1 year respectively Local gene therapy using plasmid DNA encoding acidic fibroblast growth factor (NV1FGF, riferminogene pacaplasmid) showed promising results in a phase II trial on amputation free survival. This report provides the rationale, design and baseline characteristics of CLI patients enrolled to the pivotal phase III trial (TAMARIS). It also describes baseline characteristics by diabetes status and region of origin. Table: Comparison of 6 modes of ABI calculation to predict the 5-years mortality (abstract 237). ABI mode of calculation High/High Mean/High Low/High High/Mean Mean/Mean Low/Mean AUC 0.632 * 0.620 0.615 0.610 0.618 0.598 Sensitivity with 0.90 55.7% 56.7% 60.4% 53.6% 60.8% 58.8% Specificity with 0.90 65.1% 62.3% 60.2% 63.6% 58.5% 58.6% Optimal cutpoint 0.94 0.97 0.92 1.00 0.97 0.92 Sensitivity for optimal cutpoint 63.9% 72.2% 64.6% 72.2% 74.2% 62.9% Specificity for optimal cutpoint 60.3% 50.6% 58.7% 48.3% 50.3% 57.5% * p<0.05 vs. High/Mean and Low/Mean An international, double-blind, placebo-controlled, randomized study included 525 CLI patients worldwide who were unsuitable for revascularization and had non-healing skin lesions, to evaluate whether repeated intramuscular administration of NV1FGF results in reduction of major amputations or deaths at 1 year. Mean age of the population was 70 ± 10 years including 70% males and 53% diabetic patients. Fifty four percent of the population had previous lower extremity revascularization and 22% had previous minor amputation of the index leg. Ninety six percent of patients had an ankle pressure < 70 mmHg and/or a toe pressure < 50 mmHg or a TcPO2 < 30 mmHg. In 94% the index leg had distal occlusive disease affecting arteries below the knee. Statins were prescribed in 54% of patients, and antiplatelet drugs in 80%. Variation in region of origin resulted in only minor demographic imbalance. Patients with diabetes had more risk factors including history of coronary artery disease, but were similar to non-diabetic patients regarding limb haemodynamics and vascular lesions. The clinical and vascular anatomy presentation of patients with CLI with ischemic skin lesions who were unsuitable for revascularization was homogeneous with little imbalance according to region of origin or diabetic status. The findings from this large CLI cohort are important for the understanding of the epidemiology of the disease.