14 The primary efficacy endpoint, change in peak walking time at 12 weeks, did not differ between the placebo, low-dose, and high-dose (1.5±3.1 minutes) groups. Secondary endpoints such as ankle-brachial index (ABI), claudication onset time, and quality-of-life measures were also similar among groups at 12 and 26 weeks.
However, in these patients, AdVEGF121 administration was associated with increased peripheral edema. TALISMAN 201: This study evaluated the efficacy and safety of intramuscular administration of Inhibitors,research,lifescience,medical NV1FGF, a plasmid-based fibroblast growth factor 1, versus PARP assay placebo in 125 CLI patients presenting with nonhealing ulcer(s).15 Patients were randomized to receive 8 intramuscular injections of placebo or vector on days 1, 15, 30, and 45. Both NV1FGF and placebo showed similar improvements in ulcer healing (19.6% vs. 14.3%, respectively; P = 0.514). However, the use of NV1FGF significantly reduced (by two fold) the risk of all amputations (hazard ratio Inhibitors,research,lifescience,medical [HR] 0.498; P = 0.015) and major amputations (HR 0.371 P = 0.015). WALK: The WALK trial tested whether intramuscular administration of Ad2/HIF-1α/VP16, an engineered recombinant type 2 adenovirus vector encoding constitutively active HIF-1α (hypoxia-inducible factor 1, alpha subunit), Inhibitors,research,lifescience,medical improved walking time in patients with claudication. In this randomized, placebo-controlled
study, 289 patients received 20 intramuscular injections of HIF-1α to each leg and were followed for 12 months to determine changes in peak walking time from baseline. Median peak walking time increased Inhibitors,research,lifescience,medical by 0.82 minutes in the placebo group and by 0.82 minutes, 0.28 minutes, and 0.78 minutes, respectively, in the three groups with escalating doses of HIF-1α (2×109,
2×1010, and 2×1011) viral particle (P = NS between placebo and each HIF-1α treatment group). There were no significant differences in claudication onset time, ABI, or quality-of-life measurements Inhibitors,research,lifescience,medical between the placebo and each HIF-1α group.16 HGF-STAT: In the Study to Assess the Safety of Intramuscular Injection of Hepatocyte Growth Factor Plasmid to Improve Limb Perfusion in Patients With Critical Limb Ischemia (HGF-STAT trial),17 105 patients received placebo or HGF-plasmid Sodium butyrate intramuscular injection as follows: 0.4 mg at days 0, 14, and 28 (low dose); 4.0 mg at days 0 and 28 (middle dose); or 4.0 mg at days 0, 14, and 28 (high dose). Adverse events occurred in 86% of the patients, and most were related to CLI or comorbid conditions and were not different between groups. Transcutaneous oxygen tension (TcPO2) increased at 6 months in the high-dose group compared with the placebo, low-dose, and middle-dose groups (ANCOVA P = 0.0015). There was no difference between groups in secondary endpoints, including ABI, toe-brachial index (TBI), pain relief, wound healing, or major amputation. In a follow-on study,18 patients were randomized to 3:1 HGF (n = 21) vs. placebo (n = 6). There was no difference in adverse events or serious adverse events.