07_05 Face Off p15,16
CLINICAL
TRIAL SPOTLIGHT
DENALI Trial Seeks to
Reduce Number of Treatments for Wet AMD
Trial
will combine verteporfin and ranibizumab in 2-year trial.
ANDREW E. MATHIS, PHD, MEDICAL EDITOR
Novartis
(East Hanover, NJ) announced Nov. 10 that it will be carrying out the DENALI clinical
trial, a trial designed to measure the efficacy and safety of verteporfin (Visudyne,
Novartis) in combination with photodynamic therapy (PDT) and the anti-vascular endothelial
growth factor (VEGF) agent ranibizumab (Lucentis, Genentech). This will be the first
large-scale (300 patients in the United States and Canada) study to examine the
use of verteporfin with ranibizumab for the treatment of exudative age-related macular
degeneration (AMD).
This
study will be looking at the oldest FDA-approved treatment for wet AMD (verteporfin,
approved April 2000) and the most recently approved wet AMD injection approved by
the FDA (ranibizumab, approved June 2006). Together with a European-based trial,
called MONT BLANC, the DENALI trial is party of the SUMMIT Trial Program. Both trials
take their names from the highest mountains on the continents on which they will
be taking place — thus the SUMMIT name for the program of trials.
Peter K. Kaiser, MD, director of
the Retinal Clinical Research Center at the Cole Eye Institute of the Cleveland
Clinic and the study chairman of the DENALI trial, says the key issue being examined
is whether the number of treatments for wet AMD patients can be reduced while maintaining
efficacy. "Treatments are a big inconvenience for our patients," Dr. Kaiser says.
"If, by combining treatments we know will work and we know are safe, we can reduce
the number of treatments, we will reduce that inconvenience."
The study will be designed such
that two-thirds of the patients enrolled will receive combination therapy and the
remaining third will receive ranibizumab alone. Of the two-thirds of enrollees who
receive verteporfin with PDT and ranibizumab, the investigators also intend to vary
the fluence rate of the PDT in about half of these eyes. "We want to see whether
changing the fluence rate has any effect on the efficacy of combination treatment,"
Dr. Kaiser says.
Asked whether the vision improvement
that has been documented with ranibizumab may be further improved, Dr. Kaiser responds,
"I don't think so." However, he notes, "We know that combination therapy improves
vision." The question under examination, rather, will be whether this vision improvement
can be attained with fewer treatments.
The duration of the study is expected
to be 2 years. During the first year, participants will receive 12 monthly injections
in the ranibizumab alone arm and as needed dosing after 3 monthly injections in
the combination arms. Then they will be followed for another year. Earlier trials,
such as the FOCUS, VERITAS, and PROTECH studies, were as short as 6 months. "So
far," Dr. Kaiser says, "results have been excellent when combining PDT and an anti-VEGF
treatment."
Because the DENALI trial will also
be assessing the safety of the verteporfin with PDT and ranibizumab combination,
Retinal Physician asked Dr. Kaiser whether there were any specific safety
issues for which the investigation team would be on the lookout. "There have been
excellent results combining these drugs in previous trials," Dr. Kaiser says. "There
has been little or no uveitis or endophthalmitis seen with the marketed formulation
of Lucentis, so we do not foresee any safety problems."
The primary endpoint of the study
will come after
1 year of treatment, at which point best corrected protocol visual
acuity will be measured. A key second endpoint will be the first time retreatment
for wet AMD is necessary after 1 year. Novartis has stressed that the DENALI trial
is not devised to produce additional indications for verteporfin. However, the company
will be analyzing data generated by the study before the endpoint. The DENALI trial
will begin enrolling patients in early 2007. RP
Retinal Physician, Issue: January 2007