NIH-Sponsored Study Stopped: New Drug Does Not Control AIDS-Related Eye Disease

08/15/96

Researchers have stopped patient enrollment and treatment in a studydesigned to evaluate the safety and effectiveness of a new drug totreat a blinding eye infection common in people with AIDS. The drug,MSL 109 (ProtovirTM), did not slowthe progression of CMV retinitis, the eye infection, in a clinicaltrial sponsored by the National Eye Institute (NEI) of the NationalInstitutes of Health.

At the time the study was stopped, 209 of the 325 patients plannedfor the study had been treated. Of those, approximately 40% were newlydiagnosed with CMV retinitis and 60% had previously been diagnosedwith, and treated for, the disease. The patients were randomized toreceive either MSL 109 or a placebo.

The investigators decided to terminate enrollment and treatmentfollowing the recommendation of an independent data and safetymonitoring board. The recommendation was based on the lack of evidenceof efficacy of MSL 109 for the treatment of CMV retinitis. The mediantime to progression of disease was 65 days in the group treated withMSL 109 and 66 days in the group taking the placebo.

In addition, study results suggest that patients with recurrent CMVretinitis who were taking the new drug had a higher mortality ratethan similar patients taking a placebo. However, the meaning of thismortality difference was unclear because among this same group ofstudy patients there was a lower than expected mortality rate in thosegiven the placebo. The mortality difference was not observed inpatients with newly-diagnosed CMV retinitis.

“These results highlight the importance of conducting clinicaltrials 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 iscaused by an organism called cytomegalovirus (CMV). Untreated, thedisease destroys the retina, the light-sensing tissue that lines theback of the eye and is crucial for vision.

People with AIDS are among those most vulnerable to CMV, becausetheir weakened immune systems are unable to resist potentially harmfulorganisms. Most people have been exposed to CMV, but their healthyimmune 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 thatmimics the body’s natural reaction to a foreign organism by actinglike antibodies that are produced normally in healthy humans. MSL 109mimics the body’s antibody to the CMV virus. Patients in the studyreceived either MSL 109 or a placebo as supplementary therapy to theirprimary treatment for CMV retinitis. The purpose of the study was tosee if the supplementary therapy would keep the disease from spreadingfor 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 Federalgovernment’s lead agency for vision research, and supports more than 80percent of such research conducted in the United States. The MACRT studyis part of a collaborative research group, Studies of the OcularComplications of AIDS (SOCA), which was established through the NationalInstitutes of Health. The SOCA study of MSL 109 was performed with fundingfrom the National Eye Institute and Protein Design Labs, Inc., incollaboration with the National Institute of Allergy and InfectiousDiseases’ AIDS Clinical Trials Group.

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Participating Clinical Centers
Monoclonal Antibody CMV-Retinitis Trial

Locations

California
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

Florida
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

Georgia
Daniel F. Martin, M.D.
The Emory Eye Clinic
Emory University
Atlanta
(404) 778-4815

Illinois
David V. Weinberg, M.D.
Department of Ophthalmology
Northwestern University
Chicago
(312) 908-8152

Louisiana
Bruce A. Barron, M.D.
LSU Eye Center
Louisiana State University
Medical Center
New Orleans
(504) 568-6700 ext. 307

Maryland
James P. Dunn, M.D.
The Wilmer Ophthalmological Institute
The Johns Hopkins University
School of Medicine
Baltimore
(410) 955-2966

New Jersey
Ronald Rescigno, M.D.
UMDNJ-New Jersey
Medical School
Newark
(201) 982-2065

New York
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

North Carolina
Charles van der Horst, M.D.
University of North Carolina
at Chapel Hill
(919) 966-2536

Texas
Richard Alan Lewis, M.D.
Cullen Eye Institute
Baylor College of Medicine
Houston
(713) 798-6100

Resource Centers:

Chairman’s Office
Douglas A. Jabs, M.D.
The Wilmer Ophthalmological Institute
The Johns Hopkins University School of Medicine
Baltimore, Maryland
(410) 955-1966

Coordinating Center
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

Central Laboratories/Repository:
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

NEI Representative:
Natalie Kurinij, Ph.D.
National Eye Institute
(301) 496-5983

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Citations

  • McCarthy M. CMV Retinitis Monoclonal Antibody Trial Halted. Lancet. 1996 Aug 31. PubMed

June 2001