A Phase II/III Trial of Human Anti-CMV Monoclonal Antibody MSL 109 (MACRT)

To compare the safety and efficacy of sevirumab (MSL 109; Protovir), human anti-cytomegalovirus (CMV) monoclonal antibody, plus active primary treatment versus placebo plus active primary treatment in AIDS patients with newly diagnosed and relapsed CMV retinitis.

Ganciclovir and foscarnet are used for treatment of CMV retinitis, but cause hematologic toxicity and nephrotoxicity, respectively. Despite continued maintenance therapy with these drugs, relapse occurs in 85 percent of patients within 4 months. Studies suggest that MSL 109, a human monoclonal antibody, when given with either ganciclovir or foscarnet, may increase initial response and prolong time to progression in patients with CMV retinitis.

Ganciclovir and foscarnet are used for treatment of CMV retinitis, but cause hematologic toxicity and nephrotoxicity, respectively. Despite continued maintenance therapy with these drugs, relapse occurs in 85 percent of patients within 4 months. Studies suggest that MSL 109, a human monoclonal antibody, when given with either ganciclovir or foscarnet, may increase initial response and prolong time to progression in patients with CMV retinitis.

Patients are randomized to receive either MSL 109 or placebo every 2 weeks as supplemental therapy to primary CMV treatment.

• Cytomegalovirus Retinitis
• HIV Infections

Inclusion Criteria

Concurrent Medication: Required:

• Primary CMV treatment.

Patients must have:

• AIDS.
• Active CMV retinitis.
• At least one photographable lesion of one-quarter or more optic disc area in size.
• Undergoing primary treatment for CMV retinitis that is not contraindicated with MSL 109.
• Visual acuity in at least one eye of 3 or more letters on Early Treatment Diabetic Retinopathy Study ( ETDRS ) chart at 1 meter distance ( Snellen equivalent 5/200 ). Note:
• Exceptions may be made if visual acuity impairment is possibly reversible and there is at least light perception in that eye.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Retinal detachment not scheduled for surgical repair.
• Media opacity that precludes visualization of the fundus.
• Active medical problems sufficient to hinder study compliance.

Concurrent Medication:

Excluded:

• IVIG.
• CMV immune globulin ( CMVIG ).
• Interferon alpha.
• Interferon gamma.
• Interleukin-2 ( IL-2 ).

Drug or alcohol abuse sufficient to hinder study compliance.