Transcript AGENT-3 - Clinical Trial Results

AGENT-3 Trial
A Multicenter, Prospective, Randomized Trial of
Intracoronary Administration of Ad5FGF-4 in
Patients With No Revascularization Options
(AGENT-3) Trial
Presented at
The American College of Cardiology
Scientific Sessions 2005
Presented by Dr. Timothy Henry
AGENT-3 Trial
415 patients with CCS Class 2-4 angina despite optimal medical treatment not
in need of immediate traditional revascularization strategies, able to walk between 3
& 10 minutes with inducible ST depression of at least 1 mm and variability between successive
exercise tests of 20% or less, at least 1 proximal vessel with <70% stenosis
Placebo controlled, randomized, blinded, mean follow-up 5 years (data reported for 1 year)
Amino Acid Protein
Ad5FGF-4
1*1010
virus particles
n=150
Amino Acid Protein
Ad5FGF-4
1*109 virus particles
n=150
Control
n=150
Primary Endpoint: Change in exercise tolerance test (ETT) time from baseline to 12 weeks and the
proportion of patients with 30% greater increase in treadmill exercise duration in 12 weeks.
Secondary Endpoint: Time to a number of patients with coronary events (non-fatal MI, unplanned
hospitalization or revascularization for myocardial ischemia), death at 12 months, time to ST
depression, angina, and quality of life parameters.
www. Clinical trial results.org
Presented at ACC2005
AGENT-3 Trial: Primary Endpoint
Primary endpoint of change
in ETT duration
75
69
72
71
• The primary endpoint of change in ETT
duration at 12 weeks was not significant. There
was also no change in exercise duration at 6
months.
• In a pre-specified analysis, older patients (>55
years) with more severe angina (CCS Class 3 or
4) had a significantly greater increase in ETT at
12 weeks (p=0.02 high-dose, p=0.08 low-dose)
and 6 months (p=0.08 high-dose, p=0.07 lowdose).
60
45
30
15
0
12 weeks
High-Dose
Low-dose
www. Clinical trial results.org
Control
• Similarly, older patients (>55years) with
exercise time 300 seconds or less had a
significantly greater increase in ETT time at 12
weeks (p=0.03 high-dose, p=0.06 low-dose) and
6 months (p=0.017 high-dose, p=0.03 low-dose).
Presented at ACC 2005
AGENT-3 Trial: Subgroup Analysis
p=NS
19%
20%
20%
17%
15%
•The combined endpoint of coronary
events or death at 1 year in patients
completing 12 month follow-up did
not differ significantly among the
three groups.
%
10%
5%
0%
Coronary events/death at 1 year
High-dose
Low-dose
www. Clinical trial results.org
Control
Presented at ACC 2005
AGENT-3 Trial: Summary
• This study is the largest randomized gene therapy trial for myocardial
angiogenesis.
• Ad5FGF-4 was not associated with increased exercise time compared
to placebo
• The favorable safety profile of this drug seen in this trial makes further
evaluation using higher doses possible.
• The beneficial effect demonstrated in the pre-specified subgroup
analysis of higher risk patients warrants further study.
www. Clinical trial results.org
Presented at ACC 2005