Studies of the Ocular Complications of AIDS (SOCA)--Monoclonal Antibody CMV Retinitis Trial (MACRT)

Last updated: October 14, 2015
Sponsor: Johns Hopkins Bloomberg School of Public Health
Overall Status: Completed

Phase

2/3

Condition

Hiv Infections

Cytomegalovirus Infections

Posterior Uveitis

Treatment

N/A

Clinical Study ID

NCT00000135
NEI-34
  • Ages > 13
  • All Genders

Study Summary

To evaluate the efficacy and safety of a human anti-CMV monoclonal antibody, MSL-109, as adjunct therapy for controlling CMV retinitis.

Eligibility Criteria

Inclusion

Inclusion criteria:

  • 13 years or older at entry

  • Diagnosis of AIDS according to the Centers for Disease Control and Prevention (CDC)definition

  • Diagnosis of active CMV retinitis as determined by a SOCA-certified ophthalmologist attime of enrollment

  • At least one lesion whose size is one-quarter or more optic disc area

  • Currently receiving (for relapsed patients) or scheduled to receive (for newlydiagnosed patients) drugs for primary treatment of CMV retinitis that are notcontraindicated for use with MSL-109

  • Visual acuity, in at least one eye that meets other eligibility criteria, of 3 or moreletters on ETDRS chart at 1 meter distance (Snellen equivalent 5/200). Patients withpoorer visual acuity may be enrolled if the visual acuity impairment is possiblyreversible (eg, due to optic disc edema) and vision is at least light perception inthat eye

  • Karnofsky score of 60 or more

  • Willingness and ability, with the assistance of a caregiver if necessary, to complywith treatment and follow up procedures

  • signed consent statement

Exclusion

Exclusion criteria:

  • Current treatment with intravenous immune globulin (IVIG), CMV immune globulin (CMVIG), alpha-interferon (alpha-IFN), gamma-interferon (gamma-IFN) or interleukin-2 (IL-2)

  • Media opacity that precludes visualization of the fundus in all eyes meetingeligibility criteria

  • Active medical problems, including drug or alcohol abuse, that are consideredsufficient to hinder compliance with treatment or follow up procedures

  • Retinal detachment, not scheduled for surgical repair, in all eyes meeting othereligibility criteria

Study Design

Total Participants: 209
Study Start date:
September 01, 1995
Estimated Completion Date:
August 31, 1996

Study Description

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.