Age-Related Macular Degeneration, Choroidal Neovascularization
Conditions
Keywords
Age-Related Macular Degeneration, Rapamycin, Remicade, Daclizumab, Immunosuppression, Infliximab, Choroidal Neovascularization, Sirolimus, AMD, Ocular Inflammation
Brief 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.
Detailed description
There has been much interest in the possible role of the immune system in AMD. Experimental models and patient material have, to date, suggested a role for macrophages and complement. This study hypothesized that the underlying mechanism that leads to choroidal neovascularization (CNV) is similar to those at play in atherosclerosis. If this is the case, the investigators believed that CNV treatment should be amenable to new immunomodulatory agents directed against specific parts of the immune system. After therapy with anti-angiogenic agents not leading to a persistent remission of CNV due to AMD, participants were treated with one of three immunomodulatory agents or were observed in conjunction with their continued anti-angiogenic therapy. Thus the participant continued with the anti-angiogenic therapy they received after randomization. The investigators hypothesized that this combination therapy would inhibit progression of CNV associated with AMD. This was an open-label, phase II, randomized, single center clinical trial of 18 study participants randomized to receive one of three immunomodulatory agents or was observed in conjunction with their anti-angiogenic therapy.
Interventions
DRUGIntravenous Daclizumab
Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study.
DRUGIntravenous Infliximab
Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months.
OTHERObservation
Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography.
DRUGOral Rapamycin
Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months.
Sponsors
National Eye Institute (NEI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to 92 Years
Healthy volunteers
No
Inclusion criteria
1. Understand and sign the institutional review board (IRB)-approved informed consent document for the study. 2. Age greater than 55 years. 3. In the study eye, diagnosis of AMD defined by the presence of drusen larger than 63 microns. 4. Any anti-angiogenic therapy in the study eye within 7 days of beginning immunosuppressive therapy. 5. In the study eye, the participant's study eye vision is between 20/20 and 20/400. 6. 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: 1. Early stippled hyperfluorescence of flat retinal pigment epithelium (RPE)and little or mild leakage in the late frames of the fluorescein (occult). 2. 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). 3. 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). 4. 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). 7. For all CNV lesions considered to have occult CNV with no classic CNV, one of the following criteria must be met: 1. 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 2. Documented FA evidence of a 10% increase in the lesion greatest linear dimension over the 3 months prior to enrollment. OR 3. Documented blood associated with CNV. 8. 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. 9. Retinal photographs and angiography of sufficient quality, allowing assessment of the macular area according to standard clinical practice, can be obtained. 10. 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. 11. Willingness to comply with the protocol.
Exclusion criteria
1. CNV, in the study eye, associated with other ocular diseases such as pathologic myopia, ocular histoplasmosis or posterior uveitis, etc. 2. Presence of geographic atrophy under the fovea in the study eye. 3. 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. 4. The presence of a chorio-retinal anastomosis. 5. 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 including amblyopia, anterior ischemic optic neuropathy, clinically significant diabetic macular edema, severe non-proliferative diabetic retinopathy, or proliferative diabetic retinopathy. 6. Decreased vision, in the study eye, due to significant media opacity such as corneal disease or cataract, or opacity precluding photography of the retina; a tear (rip) of the RPE; a vitelliform-like lesion of the outer retina (e.g., as in pattern dystrophies or basal laminar drusen), idiopathic parafoveal telangiectasis, or central serous retinopathy. 7. Presence of fibrosis, hemorrhage, pigment epithelial detachments and other hypofluorescent lesions obscuring greater than 50% of the CNV lesion. 8. History of other systemic antiangiogenic treatment or treatment for CNV (not including photodynamic therapy and pegaptanib sodium injections) in the study eye with transpupillary thermotherapy or other local treatment (such as submacular surgery). Previous laser photocoagulation therapy is acceptable, provided it was not subfoveal. 9. Participant with a known underlying systemic disease with evidence of serious or potentially lethal uncontrolled active disease in one or more extraocular organ systems for which a defined effective medical regimen is indicated. 10. Participant with a corneal melting, necrotizing keratitis, or impending vision loss. 11. Participants with history of allergy to/or exposure to mouse protein. 12. Participant with scleritis of infectious etiology. 13. Participant receiving any other investigational therapy or another anti-tumor necrosis factor (TNF) agent that would interfere with the ability to evaluate the safety or efficacy of infliximab. 14. Participant has significant active infection requiring hospitalization. 15. Participant with multiple sclerosis. 16. Participant has severe (class 3/4) congestive heart failure. 17. Participant has a history of cancer within the past 5 years other than basal or squamous cell carcinoma. 18. Participant is pregnant or lactating. 19. Participant with posterior scleritis. 20. Participant has evidence of liver disease (any etiology). History of moderate to severe abnormal liver function, unless documented evidence of normal liver enzymes is provided. 21. Participant has positive PPD (tuberculosis test) unless cleared by Internal Medicine. 22. Participant has positive Chest X-ray showing acute pulmonary disease. 23. Participant has unexplained hematuria. 24. Participant has a history of alkylating therapy use. 25. Current exam evidence of ocular toxoplasmosis; pseudoexfoliation; external ocular infection, including conjunctivitis; chalazion; significant blepharitis; or aphakia in the study eye (pseudophakic participants are eligible). 26. Intraocular surgery (including lens replacement surgery) within 6 weeks prior to randomization. 27. Recent history of (within the last 6 months), or current acute ocular or periocular infection (including any history of ocular herpes zoster or simplex). 28. Known hypersensitivity/allergy to verteporfin, porfimer sodium, or other porphyrins, porphyria or other porphyrin sensitivity, or hypersensitivity to sunlight or bright artificial light. Participation in any other clinical study or are receiving, or have received any experimental systemic treatment for AMD (e.g., retinoic acid, thalidomide). Local therapy for AMD is permitted. 29. Medical problems that make consistent follow-up over the treatment period unlikely (e.g., stroke, severe myocardial infarction (MI), end stage malignancy), any contraindications to performing the necessary diagnostic studies (i.e., known allergy to fluorescein dyes etc.), or in general a poor medical risk because of other systemic diseases or active uncontrolled infections. 30. Participant has a history of moderate to severe abnormal liver function, unless documented evidence of normal liver enzymes is provided. 31. Participant has a history of active pulmonary tuberculosis. 32. Participant has a history of active viral hepatitis. 33. Participant has chronic continued Ketoconazole use.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Monthly Rates of Anti-VEGF (Vascular Endothelial Growth Factor) Injections | 24 Weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Baseline and 6 months (24 weeks) - Baseline and 3.5 months for Patient 7 | The values in the table represent the denominator for the visual acuity in feet. A value of 20 represents normal 20/20 vision while increasing values for the denominator represent worsening vision. |
| Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Baseline and 6 months (24 weeks) - Baseline and 3.5 months for Patient 7 | — |
Countries
United States
Participant flow
Recruitment details
The study was conducted at the Clinical Center, NIH. A total of 13 participants met the eligibility criteria for the study and were enrolled from September 2006 to May 2008.
Participants by arm
| Arm | Count |
|---|---|
| Intravenous Daclizumab Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study. | 4 |
| Intravenous Infliximab Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months. | 3 |
| Oral Rapamycin Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months. | 3 |
| Observation Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography. | 3 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Intravenous Infliximab | Oral Rapamycin | Intravenous Daclizumab | Observation | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Continuous | 77 years STANDARD_DEVIATION 8 | 78 years STANDARD_DEVIATION 7 | 79 years STANDARD_DEVIATION 13 | 87 years STANDARD_DEVIATION 4 | 80 years STANDARD_DEVIATION 9 |
| Gender Female | 2 Participants | 3 Participants | 4 Participants | 3 Participants | 12 Participants |
| Gender Male | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 3 participants | 3 participants | 4 participants | 3 participants | 13 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 1 / 4 | 0 / 3 | 0 / 3 | 0 / 3 |
Outcome results
Primary
Monthly Rates of Anti-VEGF (Vascular Endothelial Growth Factor) Injections
Time frame: 24 Weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous Daclizumab | Monthly Rates of Anti-VEGF (Vascular Endothelial Growth Factor) Injections | 0.42 Injections per Month |
| Intravenous Infliximab | Monthly Rates of Anti-VEGF (Vascular Endothelial Growth Factor) Injections | 0.83 Injections per Month |
| Oral Rapamycin | Monthly Rates of Anti-VEGF (Vascular Endothelial Growth Factor) Injections | 0.34 Injections per Month |
| Observation | Monthly Rates of Anti-VEGF (Vascular Endothelial Growth Factor) Injections | 0.83 Injections per Month |
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
The values in the table represent the denominator for the visual acuity in feet. A value of 20 represents normal 20/20 vision while increasing values for the denominator represent worsening vision.
Time frame: Baseline and 6 months (24 weeks) - Baseline and 3.5 months for Patient 7
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Intravenous Daclizumab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Rapamycin Patient 1 | 40 Feet |
| Intravenous Daclizumab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Rapamycin Patient 7 (Baseline and 3.5 months) | 63 Feet |
| Intravenous Daclizumab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Rapamycin Patient 12t | 32 Feet |
| Intravenous Daclizumab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Daclizumab Patient 3 | 40 Feet |
| Intravenous Daclizumab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Daclizumab Patient 8 | 32 Feet |
| Intravenous Daclizumab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Daclizumab Patient 9 | 250 Feet |
| Intravenous Daclizumab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Daclizumab Patient 13 | 50 Feet |
| Intravenous Daclizumab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Infliximab Patient 2 | 40 Feet |
| Intravenous Daclizumab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Infliximab Patient 6 | 250 Feet |
| Intravenous Daclizumab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Infliximab Patient 10 | 50 Feet |
| Intravenous Daclizumab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Observation Patient 4 | 63 Feet |
| Intravenous Daclizumab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Observation Patient 5 | 50 Feet |
| Intravenous Daclizumab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Observation Patient 11 | 32 Feet |
| Intravenous Infliximab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Daclizumab Patient 3 | 40 Feet |
| Intravenous Infliximab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Observation Patient 11 | 50 Feet |
| Intravenous Infliximab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Observation Patient 4 | 63 Feet |
| Intravenous Infliximab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Infliximab Patient 2 | 32 Feet |
| Intravenous Infliximab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Rapamycin Patient 12t | 32 Feet |
| Intravenous Infliximab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Rapamycin Patient 1 | 25 Feet |
| Intravenous Infliximab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Infliximab Patient 10 | 32 Feet |
| Intravenous Infliximab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Infliximab Patient 6 | 800 Feet |
| Intravenous Infliximab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Daclizumab Patient 9 | 250 Feet |
| Intravenous Infliximab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Daclizumab Patient 8 | 32 Feet |
| Intravenous Infliximab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Rapamycin Patient 7 (Baseline and 3.5 months) | 50 Feet |
| Intravenous Infliximab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Observation Patient 5 | 25 Feet |
| Intravenous Infliximab | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Daclizumab Patient 13 | 40 Feet |
| Oral Rapamycin | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Observation Patient 4 | 40 Feet |
| Oral Rapamycin | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Daclizumab Patient 3 | 40 Feet |
| Oral Rapamycin | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Daclizumab Patient 8 | 32 Feet |
| Oral Rapamycin | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Observation Patient 11 | 200 Feet |
| Oral Rapamycin | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Daclizumab Patient 9 | 63 Feet |
| Oral Rapamycin | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Daclizumab Patient 13 | 25 Feet |
| Oral Rapamycin | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Observation Patient 5 | NA Feet |
| Oral Rapamycin | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Infliximab Patient 2 | 63 Feet |
| Oral Rapamycin | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Infliximab Patient 6 | 63 Feet |
| Oral Rapamycin | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Infliximab Patient 10 | 125 Feet |
| Oral Rapamycin | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Rapamycin Patient 1 | 400 Feet |
| Oral Rapamycin | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Rapamycin Patient 7 (Baseline and 3.5 months) | 640 Feet |
| Oral Rapamycin | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Rapamycin Patient 12t | 32 Feet |
| Observation | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Infliximab Patient 10 | 125 Feet |
| Observation | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Infliximab Patient 2 | 125 Feet |
| Observation | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Daclizumab Patient 3 | 32 Feet |
| Observation | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Rapamycin Patient 1 | 640 Feet |
| Observation | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Daclizumab Patient 13 | 20 Feet |
| Observation | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Daclizumab Patient 9 | 40 Feet |
| Observation | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Rapamycin Patient 12t | 32 Feet |
| Observation | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Rapamycin Patient 7 (Baseline and 3.5 months) | 640 Feet |
| Observation | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Daclizumab Patient 8 | 32 Feet |
| Observation | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Infliximab Patient 6 | 80 Feet |
| Observation | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Observation Patient 11 | 63 Feet |
| Observation | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Observation Patient 5 | NA Feet |
| Observation | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks | Observation Patient 4 | 25 Feet |
Secondary
Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks
Time frame: Baseline and 6 months (24 weeks) - Baseline and 3.5 months for Patient 7
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Intravenous Daclizumab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Rapamycin Patient 1 | 234 Microns |
| Intravenous Daclizumab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Rapamycin Patient 7 (Baseline and 3.5 months) | 361 Microns |
| Intravenous Daclizumab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Rapamycin Patient 12t | 327 Microns |
| Intravenous Daclizumab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Daclizumab Patient 3 | 216 Microns |
| Intravenous Daclizumab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Daclizumab Patient 8 | 185 Microns |
| Intravenous Daclizumab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Daclizumab Patient 9 | 297 Microns |
| Intravenous Daclizumab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Daclizumab Patient 13 | 329 Microns |
| Intravenous Daclizumab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Infliximab Patient 2 | 205 Microns |
| Intravenous Daclizumab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Infliximab Patient 6 | 290 Microns |
| Intravenous Daclizumab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Infliximab Patient 10 | 291 Microns |
| Intravenous Daclizumab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Observation Patient 4 | 229 Microns |
| Intravenous Daclizumab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Observation Patient 5 | 426 Microns |
| Intravenous Daclizumab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Observation Patient 11 | 318 Microns |
| Intravenous Infliximab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Daclizumab Patient 3 | 189 Microns |
| Intravenous Infliximab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Observation Patient 11 | 305 Microns |
| Intravenous Infliximab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Observation Patient 4 | 196 Microns |
| Intravenous Infliximab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Infliximab Patient 2 | 177 Microns |
| Intravenous Infliximab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Rapamycin Patient 12t | 264 Microns |
| Intravenous Infliximab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Rapamycin Patient 1 | 230 Microns |
| Intravenous Infliximab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Infliximab Patient 10 | 288 Microns |
| Intravenous Infliximab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Infliximab Patient 6 | 243 Microns |
| Intravenous Infliximab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Daclizumab Patient 9 | 196 Microns |
| Intravenous Infliximab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Daclizumab Patient 8 | 208 Microns |
| Intravenous Infliximab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Rapamycin Patient 7 (Baseline and 3.5 months) | 239 Microns |
| Intravenous Infliximab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Observation Patient 5 | 225 Microns |
| Intravenous Infliximab | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Daclizumab Patient 13 | 344 Microns |
| Oral Rapamycin | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Observation Patient 4 | 189 Microns |
| Oral Rapamycin | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Daclizumab Patient 3 | 352 Microns |
| Oral Rapamycin | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Daclizumab Patient 8 | 218 Microns |
| Oral Rapamycin | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Observation Patient 11 | 158 Microns |
| Oral Rapamycin | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Daclizumab Patient 9 | 215 Microns |
| Oral Rapamycin | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Daclizumab Patient 13 | 305 Microns |
| Oral Rapamycin | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Observation Patient 5 | 270 Microns |
| Oral Rapamycin | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Infliximab Patient 2 | 190 Microns |
| Oral Rapamycin | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Infliximab Patient 6 | 262 Microns |
| Oral Rapamycin | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Infliximab Patient 10 | 453 Microns |
| Oral Rapamycin | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Rapamycin Patient 1 | 211 Microns |
| Oral Rapamycin | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Rapamycin Patient 7 (Baseline and 3.5 months) | 242 Microns |
| Oral Rapamycin | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Rapamycin Patient 12t | 226 Microns |
| Observation | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Infliximab Patient 10 | 347 Microns |
| Observation | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Infliximab Patient 2 | 181 Microns |
| Observation | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Daclizumab Patient 3 | 206 Microns |
| Observation | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Rapamycin Patient 1 | 203 Microns |
| Observation | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Daclizumab Patient 13 | 317 Microns |
| Observation | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Daclizumab Patient 9 | 210 Microns |
| Observation | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Rapamycin Patient 12t | 205 Microns |
| Observation | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Rapamycin Patient 7 (Baseline and 3.5 months) | 186 Microns |
| Observation | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Daclizumab Patient 8 | 149 Microns |
| Observation | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Infliximab Patient 6 | 252 Microns |
| Observation | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Observation Patient 11 | 169 Microns |
| Observation | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Observation Patient 5 | 213 Microns |
| Observation | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks | Observation Patient 4 | 171 Microns |