Researchers have stopped patient enrollment and treatment in a study designed to evaluate the safety and effectiveness of a new drug to treat a blinding eye infection common in people with AIDS. The drug, MSL 109 (Protovir), did not slow the progression of CMV retinitis, the eye infection, in a clinical trial sponsored by the National Eye Institute (NEI) of the National Institutes of Health.
At the time the study was stopped, 209 of the 325 patients planned for the study had been treated. Of those, approximately 40% were newly diagnosed with CMV retinitis and 60% had previously been diagnosed with, and treated for, the disease. The patients were randomized to receive either MSL 109 or a placebo.
The investigators decided to terminate enrollment and treatment following the recommendation of an independent data and safety monitoring board. The recommendation was based on the lack of evidence of efficacy of MSL 109 for the treatment of CMV retinitis. The median time to progression of disease was 65 days in the group treated with MSL 109 and 66 days in the group taking the placebo.
In addition, study results suggest that patients with recurrent CMV retinitis who were taking the new drug had a higher mortality rate than similar patients taking a placebo. However, the meaning of this mortality difference was unclear because among this same group of study patients there was a lower than expected mortality rate in those given the placebo. The mortality difference was not observed in patients with newly-diagnosed CMV retinitis.
These results highlight the importance of conducting clinical trials to evaluate new therapies," said Carl Kupfer, M.D., National Eye Institute director. Up to 40 percent of people with AIDS develop CMV retinitis, which is caused by an organism called cytomegalovirus (CMV). Untreated, the disease destroys the retina, the light-sensing tissue that lines the back of the eye and is crucial for vision. People with AIDS are among those most vulnerable to CMV, because their weakened immune systems are unable to resist potentially harmful organisms. Most people have been exposed to CMV, but their healthy immune systems do not allow infections to develop.
The Monoclonal Antibody CMV Retinitis Trial (MACRT), a nationwide, randomized, placebo-controlled study, tested MSL 109, a drug that mimics the body's natural reaction to a foreign organism by acting like antibodies that are produced normally in healthy humans. MSL 109 mimics the body's antibody to the CMV virus. Patients in the study received either MSL 109 or a placebo as supplementary therapy to their primary treatment for CMV retinitis. The purpose of the study was to see if the supplementary therapy would keep the disease from spreading for a longer time period than their primary treatment alone. A list of centers that participated in the study is attached.
The National Eye Institute is the Federal government's lead agency for vision research, and supports more than 80 percent of such research conducted in the United States. The MACRT study is part of a collaborative research group, Studies of the Ocular Complications of AIDS (SOCA), which was established through the National Institutes of Health. The SOCA study of MSL 109 was performed with funding from the National Eye Institute and Protein Design Labs, Inc., in collaboration with the National Institute of Allergy and Infectious Diseases' AIDS Clinical Trials Group.
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Participating Clinical Centers Monoclonal Antibody CMV-Retinitis Trial
Gary N. Holland, M.D. Jules Stein Eye Institute University of California, Los Angeles (310) 825-9508
William R. Freeman, M.D. Shiley Eye Center University of California, San Diego (619) 534-3513
James O'Donnell, M.D. Beckman Vision Center University of California, San Francisco (415) 476-1921
Janet Davis, M.D. Bascom Palmer Eye Institute University of Miami (305) 326-6377
Peter R. Pavan, M.D. University of South Florida Tampa (813) 974-1530
Daniel F. Martin, M.D. The Emory Eye Clinic Emory University Atlanta (404) 778-4815
David V. Weinberg, M.D. Department of Ophthalmology Northwestern University Chicago (312) 908-8152
Bruce A. Barron, M.D. LSU Eye Center Louisiana State University Medical Center New Orleans (504) 568-6700 ext. 307
James P. Dunn, M.D. The Wilmer Ophthalmological Institute The Johns Hopkins University School of Medicine Baltimore (410) 955-2966
Ronald Rescigno, M.D. UMDNJ-New Jersey Medical School Newark (201) 982-2065
Murk-Hein Heinemann, M.D. New York Hospital-Cornell Medical Center (212) 746-2483
Alan H. Friedman, M.D. Mount Sinai School of Medicine New York City (212) 241-6241
Dorothy Friedberg, M.D. New York University Medical Center New York (212) 687-0265
Charles van der Horst, M.D. University of North Carolina at Chapel Hill (919) 966-2536
Richard Alan Lewis, M.D. Cullen Eye Institute Baylor College of Medicine Houston (713) 798-6100
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Chairman's Office Douglas A. Jabs, M.D. The Wilmer Ophthalmological Institute The Johns Hopkins University School of Medicine Baltimore, Maryland (410) 955-1966
Curtis L. Meinert, Ph.D. School of Hygiene and Public Health The Johns Hopkins University Baltimore, Baltimore (410) 955-8198
Fundus Photograph Reading Center Matthew D. Davis, M.D. Department of Ophthalmology University of Wisconsin Madison, Wisconsin (608) 263-6071
Drug Distribution Center:
Mark Walls, R.Ph. McKessan BioServices Rockville, Maryland (301) 762-0069
Richard B. Pollard, M.D. University of Texas Medical Branch Galveston, Texas (409) 772-4979
Colin Jordan, M.D. Division of Infectious Diseases University of Minnesota Minneapolis, Minnesota (612) 624-9996
Natalie Kurinij, Ph.D. National Eye Institute (301) 496-5983