Abstract 2048: Angiogenesis Protein Therapy With Human Fibroblast Growth Factor (fgf-1): Results Of A Phase I Open Label, Dose Escalation Study In Subjects With CAD Not Eligible For PCI Or CABG
Background: Although therapy for CAD has advanced with current therapies, a large number of pts have refractory angina not amenable to revascularization resulting in significant morbidity and mortality. In the current study, CAD pts were injected intramyocardially with the human FGF-1 protein at 3 escalating doses, and both safety and efficacy data were collected.
Methods: 21 pts with advanced CAD not amenable to surgery or PCI were enrolled and received 1 of 3 doses of FGF-1(141 amino acid form). The study completed follow-up in April, 2007. All pts underwent baseline testing including rest and stress SPECT scans, echo (rest and stress), ECG, angiography, Canadian ClassificationScale (CCS) Angina score, tumor marker screen, ophthalmologic exam and Seattle Angina Questionnaire (SAQ). Pts received a mini-thoracotomy; Group 1 (4 pts) received 1 μg/kg/injection, Group 2 (8 pts) received 3 μg/kg/injection, and Group 3 (9 pts) received 10 μg/kg/injection. A 1.0 mL solution of FGF-1141 containing 1000 IU heparin per mg of FGF-1141 was injected into the myocardium at the target area(s). Two injections of FGF-1141 solution were administered, according to the preop SPECT and cath. Endpoints at 6 and 12 wks included CCS score, SAQ, SPECT of the myocardium, ophthalmic exam, and ECG; coronary angiogram occurred as 12 wks.
Results: Four women and 17 men were enrolled. Based on CCS score, most pts were Class III at baseline. Mean age for Group 1 was 57 yrs and for Group 2 and 3 at 64 and 59 yrs, respectively. Review of the data on 3 occasions by the DSMC did not find any safety concerns. The SPECT scans and angiograms showed indications of improvement in myocardial perfusion in groups 2 and 3. Mean exercise time improved from 4.64 ± 2.37(SD) min at baseline to 5.80 ± 2.74(SD) min at 12 weeks. Based on the SAQ, all groups had a decrease in anginal frequency and improvement in anginal stability.
Conclusion: Angiogenesis therapy administrating the human FGF-1 protein intramyocardially is a safe and biologically active treatment for pts with advanced CAD, without revascularization options. A Phase II placebo-controlled study is planned.