Monoclonal Antibody CMV Retinitis Trial (MACRT)

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



Sponsors


Source

Johns Hopkins Bloomberg School of Public Health

Oversight Info

Has Dmc

Yes


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

Completed

Start Date

1995-09-01

Completion Date

1996-08-01

Primary Completion Date

1996-08-01

Phase

Phase 2/Phase 3

Study Type

Interventional

Primary Outcome

Measure

Time Frame

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

Enrollment

209

Conditions


Intervention

Intervention Type

Drug

Intervention Name


Description

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

Arm Group Label

MSL-109

Other Name

Monoclonal antibodies


Intervention Type

Other

Intervention Name


Description

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

Arm Group Label

Placebo



Eligibility

Criteria

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 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
(IL-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

Gender

All

Minimum Age

13 Years

Maximum Age

N/A

Healthy Volunteers

No


Verification Date

2015-07-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Sponsor


Has Expanded Access

No

Condition Browse


Number Of Arms

2

Intervention Browse

Mesh Term

Antibodies

Immunoglobulins

Antibodies, Monoclonal



Arm Group

Arm Group Label

MSL-109

Arm Group Type

Experimental

Description

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


Arm Group Label

Placebo

Arm Group Type

Placebo Comparator

Description

Placebo administered intravenous infusion every 2 weeks 60 mg.



Results Reference

Citation

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.

PMID

9400786


Citation

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.

PMID

11919489


Citation

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.

PMID

12232843


Citation

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.

PMID

12559647



Firstreceived Results Date

N/A

Acronym

MACRT

Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary Purpose

Treatment

Masking

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


ClinicalTrials.gov processed this data on August 24, 2018

Conditions

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

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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