NEI Clinical Studies
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Studies of the Ocular Complications of AIDS (SOCA)--Monoclonal Antibody CMV Retinitis Trial (MACRT)
To evaluate the efficacy and safety of a human anti-CMV monoclonal antibody, MSL-109, as adjunct therapy for controlling CMV retinitis.
CMV retinitis is the most common intraocular infection in patients with AIDS and is estimated to affect 35 to 40 percent of patients with AIDS. Untreated CMV retinitis is a progressive disorder, the end result of which is total retinal destruction and blindness. As of September 1996, drugs approved by the United States Food and Drug Administration (FDA) for the treatment of CMV retinitis were ganciclovir (Cytovene), foscarnet (Foscavir), and cidofovir (Vistide). All systemically administered anti-CMV drugs are given in a similar fashion consisting of initial 2-week high-dose treatment (induction) to control the infection followed by long-term lower dose treatment (maintenance) to prevent relapse. Ganciclovir is available in both intravenous and oral formulations, foscarnet only in an intravenous formulation, and cidofovir is given by intermittent intravenous administration. A surgically implanted intraocular sustained-release ganciclovir device (Vitrasert) is also approved by the FDA for the treatment of CMV retinitis.
Despite the use of continuous maintenance therapy, given enough time, all patients with CMV retinitis on systemically administered drugs relapse. Preliminary studies suggested that the anti-CMV monoclonal antibody, MSL-109, when administered in conjunction with ganciclovir, markedly prolonged the time to relapse. Therefore, a randomized controlled clinical trial evaluating MSL-109 as adjunct therapy was conducted.
The MACRT was a randomized, placebo-controlled, multicenter clinical trial evaluating the efficacy and safety of MSL-109 as adjunct therapy for the treatment of CMV retinitis. Patients with CMV retinitis, both those newly diagnosed and those suffering a relapse with active retinitis, were eligible. Primary therapy (e.g., ganciclovir, foscarnet, etc.) was determined by the treating local physician. The patients enrolled in the trial were randomized to either MSL-109 or placebo, administered as a rapid intravenous infusion every 2 weeks. Outcomes included survival, retinitis progression, change in amount of retinal area involved by CMV, loss of visual function (acuity and field), and morbidity.
Patients eligible for the MACRT must have been age 13 years or older and have had AIDS and CMV retinitis. Both men and women were eligible. Both patients with newly diagnosed CMV retinitis and those with an active relapse were eligible. Patients could not be treated with other immune modulators, such as intravenous immune globulin, CMV immune globulin, interferon, or interleukin 2.
Patient Recruitment Status
Completed. Patient recruitment began in September 1995 and was completed in August 1996.
Current Status of Study
The anti-CMV monoclonal antibody, MSL-109, was not effective in controlling CMV retinitis. The time to progression, rates of loss of retinal area, loss of visual acuity, and loss of visual field were similar in the MSL-109 and placebo groups. The MSL-109 group was associated with a greater mortality rate, with the excess mortality concentrated in the stratum of patients with relapsed retinitis. However, the mortality rate in the placebo-treated relapsed patients was lower than expected, and the implications of the observed mortality difference were unclear.
Douglas A. Jabs, M.D.
The Wilmer Ophthalmological Institute
Department of Ophthalmology
The Johns Hopkins University School of Medicine
550 North Broadway, Suite 700
Baltimore, MD 21205
Telephone: (410) 955-1966
Fax: (410) 955-0629
Curtis L. Meinert, Ph.D.
Department of Epidemiology
School of Hygiene and Public Health
The Johns Hopkins University
615 North Wolfe Street, Room 5010
Baltimore, MD 21205
Telephone: (410) 955-8198
Fax: (410) 955-0932
Natalie Kurinij, Ph.D.
National Eye Institute
National Institutes of Health
Executive Plaza South, Suite 350
6120 Executive Boulevard MSC 7164
Bethesda, MD 20892-7164
Telephone: (301) 496-5983
Fax: (301) 402-0528
Last Updated: 10/21/99