Table 2. Randomized, Double-Blind Trials of FGF.
| Grines et al. (21) Agent |
Grines et al. (23) Agent 2 |
Henry et al. (24) Agent 3 |
Henry et al. (24) Agent 4 |
|
|---|---|---|---|---|
| Phase | 1 | 2 | 3 | 3 |
| Patients | Chronic CAD, LVEF ≥40%, CCS class 2-3 |
Chronic CAD, LVEF ≥30%, CCS class 4 |
CAD not requiring immediate revascularization, LVEF ≥30%, CCS class 2–4 (U.S.) |
“No-option” CAD patients, LVEF ≥30%, CCS class 2-4 (Europe, Latin America, Canada) |
| Therapy | Ad5FGF-4 | Ad5FGF-4 | Ad5FGF-4 | Ad5FGF-4 |
| Delivery route | Intracoronary | Intracoronary | Intracoronary | Intracoronary |
| Duration of follow-up | 12 weeks | 8 weeks | 12 weeks | 12 weeks |
| Primary end point | Safety and feasibility | Δ RPDS | Δ ETT | Δ ETT |
| Assessment modality | Clinical and exercise treadmill test | Adenosine SPECT | Exercise treadmill test | Exercise treadmill test |
| Secondary end point | Δ Exercise time | Δ Defect size | Δ CCS class, coronary events, or death at 1 year, Δ QOL, time to ST-segment depression during exercise, proportion of patients with ≥30% increase in ETT |
|
| Treatment groups | FGF (n = 60) Placebo (n = 19) |
FGF (n = 35) Placebo (n = 17) |
High-dose (n = 140) Low-dose (n = 137) Placebo (n = 139) |
High-dose (n = 35) Low-dose (n = 43) Placebo (n = 38) |
| Dose | 108.5-1010.5 vp | 1010 vp | High-dose: 1010 vp Low-dose: 109 vp Placebo = NA |
High-dose: 1010 vp Low-dose: 109 vp Placebo = NA |
| Findings | Trend toward ↑ in exercise time with therapy |
Lower rates of revascularization at 1 year with therapy. ↓ in RPDS with therapy from baseline to follow-up*; no change in CCS score (not primary end point) |
Potential therapeutic benefit among older patients with more severe angina |
— |
| Pooled analysis: placebo effect much greater in men than women. Women had improved CCS class and ETT with therapy* | ||||
| Notes | — | One outlier in placebo group had 50% ↓ in RPDS |
Enrollment ended early when interim analysis indicated that the primary end point was unlikely to differ significantly between groups |
|
*
p ≤ 0.05.
Ad = adenoviral; CAD = coronary artery disease; CCS = Canadian Cardiovascular Society; ETT = exercise treadmill time; FGF = fibroblast growth factor; LVEF = left ventricular ejection fraction; NA = not applicable; QOL = quality of life; RPDS = reversible perfusion defect size; SPECT = single-photon emission computed tomography; vp = viral particles; Δ = change; ↑ = increase; ↓ = decline.