CLINICAL TRIAL SPOTLIGHT

READing is Fundamental

The third READ trial is beginning, testing high-dose ranibizumab in diabetic macular edema.

ANDREW E. MATHIS, PhD, MEDICAL EDITOR

With the first two READ (Ranibizumab for Edema of the mAcula in Diabetes) clinical trials, study investigators at 14 centers across the United States, led by Quan Dong Nguyen, MD, MSc, associate professor of ophthalmology at the Wilmer Eye Institute of the Johns Hopkins University, sought to determine whether ranibizumab, commonly used to treat neovascular age-related macular degeneration, could be effective in treating diabetic macular edema.

The READ-2 study, which is in its third year of subject follow-up, is a multicenter, randomized clinical study comparing ranibizumab to laser or combination therapy of laser with ranibizumab in eyes with DME. The primary outcome results of the READ-2 study were published in the November 2009 issue of Ophthalmology and demonstrated that intravitreal ranibizumab was superior to laser in improving visual acuity and reducing excess foveal thickness over a six-month period.

HIGH DOSE, HIGH HOPES

The READ-3 clinical trial has recently begun enrolling. READ-3 is a multicenter, randomized clinical trial to investigate the safety and efficacy of high-dose ranibizumab (2.0 mg) compared to standard-dose ranibizumab (0.5 mg) in eyes with DME. The READ-3 trial is sponsored by the Juvenile Diabetes Research Foundation, and the study drug will be provided by Genentech.

Dr. Nguyen indicated that one of the primary investigations in the READ-3 study will be to determine if eyes treated with the high-dose ranibizumab experience a longer duration of drug action compared to standard-dose ranibizumab. If the high-dose ranibizumab has a longer duration of action, subjects may be able to receive fewer injections to treat their DME.

The READ-3 study will also be monitoring the safety of high-dose ranibizumab in patients with diabetes. In the SAILOR (Safety Assessment of Intravitreal Lucentis for AMD) study, which evaluated the safety of 0.3 mg and 0.5 mg ranibizumab in subjects with neovascular age-related macular degeneration, an interim analysis suggested a possible increased risk for stroke with the 0.5-mg dose. However, at the conclusion of the SAILOR study, there was no evidence to suggest an increased risk of stroke or arteriothrombotic events with the 0.5-mg ranibizumab dose.

“The READ-3 investigators will be closely evaluating both the safety and efficacy of the two different doses of ranibizumab that are used in this study,” Dr. Nguyen told Retinal Physician. “Our experience with the READ-2 study did not show any safety signals associated with frequent ranibizumab treatments in subjects with DME.”

Long-term data on the effects of ranibizumab in eyes with DME are important and the READ-2 trial is still evaluating subjects through the third year of the study. “It is very critical to determine if the efficacy of ranibizumab is sustained through two and even three years of treatment,” Dr. Nguyen emphasized. The two-year follow-up results will be presented at the upcoming 2010 ARVO Annual Meeting in May.

The READ-3 trial is currently enrolling subjects at 14 clinical centers throughout the United States: in California, Florida, Georgia, Hawaii, Illinois, Kansas, Maryland, Pennsylvania, South Dakota and Texas. The Retinal Imaging Research and Reading Center at the Wilmer Eye Institute serves as the reading center for the READ-3 study.

Through the READ studies — which represent the first major collaboration in ophthalmology among nonprofit organizations, pharmaceutical companies, and academic and private clinical centers — as well as other clinical trials that are being conducted, clinician scientists are hopeful that there will be more effective treatments available for patients with diabetic macular edema in the near future.

More information on the READ-3 study can be found at the study Web site (www.read3.net) and JDRF Web site (www.jdrf.org). RP