CLINICAL TRIAL SPOTLIGHT

CATT Trial Finally Set to Enroll

After more than 1 year of waiting, all systems are go.

ANDREW E. MATHIS, PhD, MEDICAL EDITOR

Since the approval by the Food and Drug Administration (FDA) of ranibizumab (Lucentis, Genentech) for the treatment of exudative agerelated macular degeneration (AMD) in June 2006, retinal physicians and researchers have been awaiting a "head-to-head" trial comparing the safety and efficacy of ranibizumab with its parent drug, bevacizumab (Avastin, Genentech), approved by the FDA for the treatment of metastatic colon cancer but used off-label for wet AMD for the last few years. Finally, after over a year of negotiations and red tape, the Comparison of Age-related macular degeneration Treatments Trials (CATT) study is set to begin in January 2008. Daniel F. Martin, MD, study chairman for the CATT, spoke to Retinal Physician about the study, the ordeals of getting it under way, and what the trial is really trying to prove.

"We began working on this trial in fall 2005, submitted it to the National Institutes of Health [NIH] in January 2006, asked for expedited review, and received approval in October 2006," said Dr. Martin. "For a clinical trial of this magnitude, that is a remarkable turnaround time. We knew that getting NIH approval was just the first step in this process. Equally important was reaching agreement with the Centers for Medicare and Medicaid Services [CMS] on several key issues, so we began those discussions even before we had final NIH approval."

Asked why it took from October 2006 to July 2007 to finally get the trial off the ground, Dr. Martin said, "This trial raised a number of important issues regarding CMS payment policies for patients participating in a clinical trial. Some of these issues had not previously been explored. First, we needed clarification as to what CMS could cover, particularly since the treatments that we were comparing were essentially standard of care. There was nothing truly experimental. To our surprise, CMS ruled that they could not pay for ranibizumab under the existing clinical trial policy. We therefore began working with CMS to revise the policy. This wound up being the primary delay in the start of the study."

Dr. Martin continued, "On July 9, 2007, the Revised Medicare Clinical Trial Policy was published, which contained explicit language that allowed CMS to pay for ranibizumab in this study. Our trial became the change agent for this policy."

Speaking further on a few other details of the CATT study, Dr. Martin said, "This study has 2 primary purposes. The first is the best known and that is to compare the safety and efficacy of bevacizumab and ranibizumab. The second, however, is just as important as the first," he continued. "In fact, the result of this second question may have a bigger impact than the first. The second purpose is to determine whether or not as-needed dosing can produce a visual result that is as robust as what has previously been demonstrated with fixed dosing. As-needed dosing is by far the most common way that both drugs are given and yet there are little data to support this practice. It may be that we are compromising long-term outcomes by allowing these relapses to occur."

The trial is designed so that 1200 patients will be randomized into 4 arms: ranibizumab every 4 weeks, bevacizumab every 4 weeks, ranibizumab prn, and bevacizumab prn. Outcomes will be measured at the 1-year and 2-year marks. RP

Enrollment for the CATT study will begin in January.