Cytomegalovirus Retinitis, HIV Infections
Conditions
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.
Interventions
DRUGMSL-109
60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout.
OTHERPlacebo
60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout.
Sponsors
Johns Hopkins Bloomberg School of Public Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. . |
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 details
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,.
Participants by arm
| Arm | Count |
|---|---|
| MSL-109 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. | 104 |
| Placebo 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. | 105 |
| Total | 209 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 27 | 14 |
Baseline characteristics
| Characteristic | Total | MSL-109 | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 209 Participants | 104 Participants | 105 Participants |
| Region of Enrollment United States | 209 participants | 104 participants | 105 participants |
| Sex: Female, Male Female | 22 Participants | 11 Participants | 11 Participants |
| Sex: Female, Male Male | 187 Participants | 93 Participants | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 104 | 0 / 105 |
| serious Total, serious adverse events | 0 / 104 | 0 / 105 |
Outcome results
Primary
Mortality Rate
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MSL-109 | Mortality Rate | 0.68 deaths per person-year |
| Placebo | Mortality Rate | 0.31 deaths per person-year |