Clinical Trial Spotlight

The One-L LAMA

Can ranibizumab help patients with low vision in addition to AMD?

ANDREW E. MATHIS, PhD, MEDICAL EDITOR

Despite its demonstrated efficacy in treating patients with neovascular age-related macular degeneration, ranibizumab (Lucentis, Genentech) has not been tested in patients with AMD who also have low vision, ie, visual acuity of 20/400 or worse.

The LAMA trial, which just received FDA approval to begin enrollment, will seek to determine whether ranibizumab can be useful for such patients. The randomized, single-blind, placebo-control, single-group–assignment phase 2 efficacy study will enroll 40 patients from the San Francisco Bay Area. Study director Steven Sanislo, MD, spoke with Retinal Physician about the trial.

LOW VISION AND LUCENTIS

Although there is obviously a high correlation between AMD and extreme vision loss, patients with low vision were not recruited for the clinical trials that led to the approval of ranibizumab. Dr. Sanislo explained, "Patients with very poor vision or advanced disease were not included in the pivotal trials for Lucentis because it was thought that they may not respond as well to treatment or have the capacity for much gain in vision compared to patients with less severe disease."

Thus, there remained the need for a study such as LAMA, which stands for Lucentis in Advanced Macular Degeneration. The trial will randomize the 40 patients. Dr. Sanislo intends to enroll into two arms. One arm will consist of patients receiving three monthly injections of ranibizumab (0.5 mg) and then treatment as needed; the other arm will be given six monthly 0.5-mg doses and then as-needed therapy. Retreatment will be at the discretion of the physician, and, according to the protocol for the study, may be given as often as every 22 days, after the first three or six injections have been given.

Asked about the endpoints of the trial, Dr. Sanislo provided a mix of diagnostic tools for both AMD and low vision. "We have multiple study endpoints, including change in ETDRS visual acuity, thickness as measured by optical coherence tomography, and fluorescein angiography," he said. He expects it to take at least six months for the trial to be fully enrolled.

"However," Dr. Sanislo continued, "we are also looking at endpoints that are uncommon in prior studies but are particularly helpful in evaluating visual function in low-vision patients." The criteria Dr. Sanislo listed included contrast sensitivity, change in scotoma size on microperimetry, change in reading speed, and change in time for activities of daily living (TIADL).

It's clear that Genentech has an interest in approval for ranibizumab in patients with low vision, as it is one of the sponsors of the LAMA trial, along with Stanford University, where Dr. Sanislo is professor of ophthalmology, California Pacific Eye Center, and Pacific Eye Associates.

LOW VISION AND AVASTIN

Asked whether patients with low vision had been included in clinical trials for either bevacizumab (Avastin, Genentech) or pegaptanib sodium (Macugen, Eyetech), Dr. Sanislo referred to a study published last year in Retina. The article, written by Ehrlich and colleagues, described the outcome of using bevacizumab in patients with low vision.

"This was a retrospective trial that showed evidence of a benefit in terms of visual acuity and thickness on OCT," Dr. Sanislo said. "However, this trial did not look at other measures of visual function in evaluating patients with low vision."

And that's where the LAMA trial is unique. Not only are the investigators measuring changes in visual acuity from baseline and thickness on OCT, they will be including in their primary and secondary endpoints such outcomes as reading performance at six and 12 months and scotoma size, contrast sensitivity, and TIADL, at the same intervals.

For more information on the LAMA trial, visit www.clinicaltrials.gov/ct2/show/NCT00745667. RP