Phase 2
N=13
Infliximab, Sirolimus and Daclizumab to Treat Age-Related Macular Degeneration
Age-Related Macular Degeneration · Choroidal Neovascularization
Bottom Line
View on ClinicalTrials.gov: NCT00304954 ↗Enrolled (actual)
13
Serious AEs
7.7%
Results posted
Apr 2011
Primary outcome: Primary: Monthly Rates of Anti-VEGF (Vascular Endothelial Growth Factor) Injections — 0.42; 0.83; 0.34; 0.83 Injections per Month
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Intravenous Daclizumab (Drug); Intravenous Infliximab (Drug); Observation (Other); Oral Rapamycin (Drug)
- Age
- Adult, Older Adult · 55+ yrs
- Sex
- All
- Sponsor
- National Eye Institute (NEI)
- Primary completion
- Jan 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Monthly Rates of Anti-VEGF (Vascular Endothelial Growth Factor) Injections |
0.42; 0.83; 0.34; 0.83 | — |
| SECONDARY Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks |
40; 25; 400; 640; 63; 50 | — |
| SECONDARY Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks |
234; 230; 211; 203; 361; 239 | — |
Summary
This study examined whether the anti-inflammatory medicines infliximab, sirolimus or daclizumab, when given with a participant's current therapies, would prevent the growth of new blood vessels in the eye in participants with age-related macular degeneration (AMD).
Participants 55 years of age and older with AMD and drusen larger than 63um may be eligible for this study. Vision in the study eye was between 20/20 and 20/400.
Participants were randomly assigned to one of three treatments - infliximab, sirolimus, or daclizumab - or to observation only. In addition, participants may have been treated by their ophthalmologist as needed for their AMD.
Infliximab and daclizumab were given intravenously (through a vein); infusions were given at enrollment in the study, then at 2 weeks, and then monthly.
Sirolimus was a pill that was taken every other day for the duration of the study. At 6 months, participants were evaluated to see whether continuing treatment would be beneficial.
In addition to treatment or observation, participants underwent the following procedures:
Physical examination at enrollment and 6 months.
Photographs of the back of the eye, fluorescein angiography, indocyanine green angiography and measurement of retinal thickness at enrollment and months 1, 3 and 6.
* Fluorescein angiography evaluated the eye's blood vessels. A yellow dye was injected into an arm vein and traveled to the blood vessels in the eyes. Pictures of the retina were taken using a camera that flashed a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating possible blood vessel abnormality.
* Indocyanine green angiography identified feeder vessels that may have supplied abnormal blood vessels. This procedure is similar to fluorescein angiography, but uses a green dye and flashes an invisible light.
* Optical coherence tomography measures retinal thickness. This test shines a light into the eye and produces cross-sectional pictures of the retina. These measurements are repeated during the study to determine whether retinal thickening is getting better or worse, or staying the same.
Tuberculin skin test and chest x-ray at enrollment and 6 months.
Blood tests at enrollment and months 1, 3 and 6.
Eligibility Criteria
INCLUSION CRITERIA
- Understand and sign the institutional review board (IRB)-approved informed consent document for the study.
- Age greater than 55 years.
- In the study eye, diagnosis of AMD defined by the presence of drusen larger than 63 microns.
- Any anti-angiogenic therapy in the study eye within 7 days of beginning immunosuppressive therapy.
- In the study eye, the participant's study eye vision is between 20/20 and 20/400.
- In the study eye, the presence of CNV under the fovea determined by the investigators and defined as any one of the following fluorescein angiographic (FA) features:
- Early stippled hyperfluorescence of flat retinal pigment epithelium (RPE)and little or mild leakage in the late frames of the fluorescein (occult).
- Irregular elevation of the RPE that does not exhibit discrete or bright hyperfluorescence in the early transit phase of the angiogram. Stippled hyperfluorescence may be present. Late frames may show persistent fluorescein staining or leakage within a sensory retinal detachment overlying this area (occult).
- Late-phase leakage of undetermined source with leakage at the level of the RPE in the late-phase frames of the angiogram in which the source of the late leakage cannot be determined from earlier-phase frames of the angiogram (occult).
- A well-demarcated area of bright hyperfluorescence in the early phase of the angiogram with leakage through the mid- and late-phase frames which obscures the boundaries of the area (classic).
- For all CNV lesions considered to have occult CNV with no classic CNV, one of the following criteria must be met:
- A documented loss of visual acuity (5 or more letters of best-corrected visual acuity if both measurements are made using an Early Treatment for Diabetic Retinopathy Study (ETDRS) chart or, a doubling of the visual angle if Snellen acuities are available from either an outside referral center or within the participating center (e.g., 20/80 to 20/160) a doubling of the visual angle is required because of the measurement variability of Snellen acuities).
OR
- Documented FA evidence of a 10% increase in the lesion greatest linear dimension over the 3 months prior to enrollment.
OR
- Documented blood associated with CNV.
- The greatest linear dimension of the entire lesion (classic CNV, occult CNV and any features that could obscure the identification of classic or occult CNV) has to be less than or equal to 5400 microns in greatest linear dimension on the retina as measured by the treating ophthalmologist.
- Retinal photographs and angiography of sufficient quality, allowing assessment of the macular area according to standard clinical practice, can be obtained.
- Women of childbearing potential must not be pregnant or lactating, must have a negative pregnancy test at screening and must be practicing an adequate method of birth control. Acceptable methods of birth control include intrauterine device (IUD); oral, dermal, implanted or injected contraceptives; tubal ligation; and barrier methods with spermicide.
- Willingness to comply with the protocol.
EXCLUSION CRITERIA
- CNV, in the study eye, associated with other ocular diseases such as pathologic myopia, ocular histoplasmosis or posterior uveitis, etc.
- Presence of geographic atrophy under the fovea in the study eye.
- Evidence of retinal angiomatous proliferation as suspected by the presence of intraretinal hemorrhage, intraretinal leakage, adjoining serous pigment epithelial detachment (PED) or the presence of a connecting retinal vessel.
- The presence of a chorio-retinal anastomosis.
- Decreased vision, in the study eye, due to retinal disease not attributable to CNV, such as nonexudative forms of AMD, geographic atrophy, inherited retinal dystrophy, uveitis or epiretinal membrane. Participants who have any additional ocular diseases that have irreversibly compromised or, during follow-up, could likely compromise the visual acuity (VA) of the study eye in
Data sourced from ClinicalTrials.gov (NCT00304954). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.