Monoclonal Antibody CMV Retinitis Trial (MACRT)

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



Johns Hopkins Bloomberg School of Public Health

Oversight Info

Has Dmc


Brief Summary

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

Detailed 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.

Overall Status


Start Date


Completion Date


Primary Completion Date



Phase 2/Phase 3

Study Type


Primary Outcome


Time Frame

Mortality Rate
All patients enrolled were followed for a 17 month period or until a common study closing date





Intervention Type


Intervention Name


60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout.

Arm Group Label


Other Name

Monoclonal antibodies

Intervention Type


Intervention Name


60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout.

Arm Group Label




Inclusion criteria:

- 13 years or older at entry

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

- Diagnosis of active CMV retinitis as determined by a SOCA-certified ophthalmologist at
time 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 newly
diagnosed patients) drugs for primary treatment of CMV retinitis that are not
contraindicated for use with MSL-109

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

- Karnofsky score of 60 or more

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

- signed consent statement

Exclusion criteria:

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

- Media opacity that precludes visualization of the fundus in all eyes meeting
eligibility criteria

- Active medical problems, including drug or alcohol abuse, that are considered
sufficient to hinder compliance with treatment or follow up procedures

- Retinal detachment, not scheduled for surgical repair, in all eyes meeting other
eligibility criteria



Minimum Age

13 Years

Maximum Age


Healthy Volunteers


Verification Date


Lastchanged Date


Firstreceived Date


Responsible Party

Responsible Party Type


Has Expanded Access


Condition Browse

Number Of Arms


Intervention Browse

Mesh Term



Antibodies, Monoclonal

Arm Group

Arm Group Label


Arm Group Type



The dose MSL-109 administered by intravenous infusion every 2 weeks 60 mg.

Arm Group Label


Arm Group Type

Placebo Comparator


Placebo administered intravenous infusion every 2 weeks 60 mg.

Results Reference


MSL-109 adjuvant therapy for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome: the Monoclonal Antibody Cytomegalovirus Retinitis Trial. The Studies of Ocular Complications of AIDS Research Group. AIDS Clinical Trials Group. Arch Ophthalmol. 1997 Dec;115(12):1528-36. Erratum in: Arch Ophthalmol 1998 Mar;116(3):296.




Jabs DA, Gilpin AM, Min YI, Erice A, Kempen JH, Quinn TC; Studies of Ocular Complications of AIDS Research Group. HIV and cytomegalovirus viral load and clinical outcomes in AIDS and cytomegalovirus retinitis patients: Monoclonal Antibody Cytomegalovirus Retinitis Trial. AIDS. 2002 Apr 12;16(6):877-87.




Davidson M, Min YI, Holbrook JT, Van Natta M, Quinn TC, Murphy RL, Welch W, Jabs DA, Meinert CL; Studies of Ocular Complications of AIDS Research Group. Influence of filgrastim (granulocyte colony-stimulating factor) on human immunodeficiency virus type 1 RNA in patients with cytomegalovirus retinitis. J Infect Dis. 2002 Oct 1;186(7):1013-8. Epub 2002 Aug 29.




Gilpin AM, Holbrook JT, Jabs DA, Meinert CL; Studies of Ocular Complications of AIDS Research Group. Data and safety monitoring board deliberations resulting in the early termination of the Monoclonal Antibody Cytomegalovirus Retinitis Trial. Control Clin Trials. 2003 Feb;24(1):92-8.



Firstreceived Results Date




Firstreceived Results Disposition Date


Study Design Info



Intervention Model

Parallel Assignment

Primary Purpose



Double (Participant, Care Provider)

Study First Submitted

September 23, 1999

Study First Submitted Qc

September 23, 1999

Study First Posted

September 24, 1999

Last Update Submitted

October 14, 2015

Last Update Submitted Qc

October 14, 2015

Last Update Posted

November 17, 2015

Results First Submitted

June 12, 2015

Results First Submitted Qc

October 14, 2015

Results First Posted

November 17, 2015 processed this data on August 24, 2018


Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.

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