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

• Sponsor: Johns Hopkins Bloomberg School of Public Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT00000135
• Collaborator: (none)
• Enrollment: 209
• Arms: 2
• Duration (Months): 11

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
HIV Infections; Cytomegalovirus Retinitis	Drug: MSL-109; Other: Placebo	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 209 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Monoclonal Antibody CMV Retinitis Trial (MACRT)
• Study Start Date: Sep 1, 1995
• Actual Primary Completion Date: Aug 1, 1996
• Actual Study Completion Date: Aug 1, 1996

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MSL-109 The dose MSL-109 administered by intravenous infusion every 2 weeks 60 mg.	Drug: MSL-109; 60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout.; Other Names: Monoclonal antibodies
Placebo Comparator: Placebo Placebo administered intravenous infusion every 2 weeks 60 mg.	Other: Placebo; 60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout.

Outcome Measures

Primary Outcome Measures

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

   to evaluate the efficacy of an intravenous human monoclonal antibody to cytomegalovirus (CMV), MSL-109, as adjuvant treatment for CMV retinitis. .

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Johns Hopkins Bloomberg School of Public Health

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins Bloomberg School of Public Health
• ClinicalTrials.gov Identifier: NCT00000135
• Other Study ID Numbers: NEI-34
• First Posted: Sep 24, 1999
• Last Update Posted: Nov 17, 2015
• Last Verified: Jul 1, 2015

• Additional relevant MeSH terms: Cytomegalovirus Retinitis; Retinitis

Study Results

Participant Flow

Recruitment Details	Randomization was stratified on the basis of whether patients had untreated or relapsed retinitis. Primary drug therapy for CMV retinitis was determined by the treating physician.
Pre-assignment Detail	Two hundred and nine patients with acquired immunodeficiency syndrome and active CMV retinitis were enrolled in a multicenter, phase 2/3, randomized, placebo controlled clinical trial. Patients received adjuvant treatment with MSL-109, 60mg intravenously every 2 weeks, or placebo,.

Arm/Group Title	MSL-109	Placebo
Arm/Group Description	The dose MSL-109 administered by intravenous infusion every 2 weeks 60 mg. MSL-109: 60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout.	Placebo administered intravenous infusion every 2 weeks 60 mg. MSL-109: 60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout.
Period Title: Overall Study
STARTED	104	105
COMPLETED	77	91
NOT COMPLETED	27	14

Baseline Characteristics

Arm/Group Title	MSL-109	Placebo	Total
Arm/Group Description	The dose MSL-109 administered by intravenous infusion every 2 weeks 60 mg. MSL-109: 60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout.	Placebo administered intravenous infusion every 2 weeks 60 mg. MSL-109: 60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout.	Total of all reporting groups
Overall Participants	104	105	209
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	104 100%	105 100%	209 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	11 10.6%	11 10.5%	22 10.5%
Male	93 89.4%	94 89.5%	187 89.5%
Region of Enrollment (participants) [Number]
United States	104 100%	105 100%	209 100%

Outcome Measures

1. Primary Outcome

Title	Mortality Rate
Description	to evaluate the efficacy of an intravenous human monoclonal antibody to cytomegalovirus (CMV), MSL-109, as adjuvant treatment for CMV retinitis. .
Time Frame	All patients enrolled were followed for a 17 month period or until a common study closing date

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MSL-109	Placebo
Arm/Group Description	The dose MSL-109 administered by intravenous infusion every 2 weeks 60 mg. MSL-109: 60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout.	Placebo administered intravenous infusion every 2 weeks 60 mg. MSL-109: 60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout.
Measure Participants	104	105
Number [deaths per person-year]	0.68	0.31

Adverse Events

Time Frame	11 months
Arm/Group Title	MSL-109		Placebo
Arm/Group Description	The dose MSL-109 administered by intravenous infusion every 2 weeks 60 mg. MSL-109: 60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout.		Placebo administered intravenous infusion every 2 weeks 60 mg. MSL-109: 60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout.
All Cause Mortality
	MSL-109		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	MSL-109		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/104 (0%)		0/105 (0%)
Other (Not Including Serious) Adverse Events
	MSL-109		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/104 (0%)		0/105 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.