Exudative Age-related Macular Degeneration
Conditions
Keywords
Exudative Age-related Macular Degeneration, Proton beam irradiation, ranibizumab, bevacizumab, anti-VEGF therapy
Brief summary
The purpose of this study is to test the hypothesis that proton beam irradiation combined with intravitreal anti-VEGF therapy is safe and potentially more effective than intravitreal anti-VEGF therapy alone in eyes with exudative age-related macular degeneration.
Detailed description
Radiation combined with anti-VEGF therapy has been shown to be synergistic in treating cancer and result in sustained tumor regression. On-going clinical trials have shown potential synergism between intravitreal anti-VEGF therapy and epiretinal brachytherapy administered during vitrectomy surgery in treating eyes with exudative age-related macular degeneration (eAMD). In this study, we test the hypothesis that radiation to the macula administered noninvasively via proton beam is well-tolerated in eyes with eAMD when combined with intravitreal anti-VEGF therapy and that this combination therapy may act synergistically to result in sustained treatment effect in eyes with eAMD.
Interventions
DRUG24GyE proton and Anti-VEGF
24GyE proton beam will be administered in 2 fractions 24 hrs apart 2 to 6 weeks after intravitreal anti-VEGF therapy
DRUG16GyE and anti-VEGF
16GyE of Proton Beam Irradiation will be administered in 2 fractions 24 hrs apart 2 to 6 weeks after intravitreal anti-VEGF therapy
DRUGSham Irradiation and anti-VEGF
2 Sessions of Sham Proton Beam Irradiation 24 hrs apart administered 2 to 6 weeks after intravitreal anti-VEGF therapy
Sponsors
University of California, San Francisco
University of California, Davis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects will be eligible if the following criteria are met: * Ability to provide written informed consent and comply with study assessments for the full duration of the study * Age \> 50 years * Patient related considerations * Able to maintain follow-up for at least 24 months. * Women must be postmenopausal without a period for at least one year. * Diagnosed with Age-related Macular Degeneration (ARMD) with active subfoveal choroidal neovascular membrane (CNVM), newly diagnosed or treated with first dose of anti-VEGF therapy within 6 weeks of enrollment * Visual acuity 20/40 to 20/400 * Lesion size \< 12 Disc Area * Submacular hemorrhage less than 75% of total lesion and not involving foveal center * Submacular fibrosis less than 25% of total lesion * Candidate for intravitreal anti-VEGF therapy
Exclusion criteria
* Subjects who meet any of the following criteria will be excluded from this study: * Prior enrollment in the study * Pregnancy (positive pregnancy test) or lactation * Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated * Participation in another simultaneous medical investigation or trial * Previous treatment with Photodynamic Therapy (PDT) or thermal laser in study eye * Anti-VEGF therapy within 6 weeks * Intravitreal or subtenon's Kenalog within 6 months * Intraocular surgery within 3 months or expected in the next 6 months * Current or planned participation in other experimental treatments for wet AMD * Other concurrent retinopathy or optic neuropathy * Other causes of CNVM, i.e. myopic degeneration or ocular histoplasmosis (POHS) * Significant media opacity precluding adequate view of the fundus for exam, photography or OCT * History of radiation therapy to the head or study eye * Diabetes mellitus or hemoglobin A1c \> 6 * Head tremor or h/o claustrophobia precluding positioning for proton irradiation * Inability to maintain steady fixation with either eye * History of Malignancy treated within 5 years * Allergy to Fluorescein dye
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Eyes With Severe Ocular Adverse | Month 24 | vision loss of 3 or more lines associated with radiation retinopathy or papillopathy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Anti-VEGF Injections Administered | Month 24 | efficacy measure |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 24GyE + Anti-VEGF 24GyE proton and Anti-VEGF: 24GyE proton beam will be administered in 2 fractions 24 hrs apart 2 to 6 weeks after intravitreal anti-VEGF therapy | 12 |
| 16GyE + Anti-VEGF 16GyE and anti-VEGF: 16GyE of Proton Beam Irradiation will be administered in 2 fractions 24 hrs apart 2 to 6 weeks after intravitreal anti-VEGF therapy | 11 |
| Sham Irradiation + Anti-VEGF Sham Irradiation and anti-VEGF: 2 Sessions of Sham Proton Beam Irradiation 24 hrs apart administered 2 to 6 weeks after intravitreal anti-VEGF therapy | 11 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 6 | 7 | 4 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | 24GyE + Anti-VEGF | 16GyE + Anti-VEGF | Sham Irradiation + Anti-VEGF |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 34 Participants | 12 Participants | 11 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| best corrected visual acuity | 0.62 logMAR BCVA STANDARD_DEVIATION 0.38 | 0.72 logMAR BCVA STANDARD_DEVIATION 0.39 | 0.59 logMAR BCVA STANDARD_DEVIATION 0.51 | 0.55 logMAR BCVA STANDARD_DEVIATION 0.18 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 34 Participants | 12 Participants | 11 Participants | 11 Participants |
| Region of Enrollment United States | 34 participants | 12 participants | 11 participants | 11 participants |
| Sex: Female, Male Female | 18 Participants | 6 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Male | 16 Participants | 6 Participants | 5 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 4 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 1 / 4 | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 4 | 0 / 6 |
Outcome results
Primary
Percent of Eyes With Severe Ocular Adverse
vision loss of 3 or more lines associated with radiation retinopathy or papillopathy
Time frame: Month 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 24GyE PBT | Percent of Eyes With Severe Ocular Adverse | 0 percentage of participants |
| 16GyE PBT | Percent of Eyes With Severe Ocular Adverse | 0 percentage of participants |
| Sham Radiation | Percent of Eyes With Severe Ocular Adverse | 0 percentage of participants |
Secondary
Number of Anti-VEGF Injections Administered
efficacy measure
Time frame: Month 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 24GyE PBT | Number of Anti-VEGF Injections Administered | 4.67 number of anti-VEGF injections per eye | Standard Deviation 1.9 |
| 16GyE PBT | Number of Anti-VEGF Injections Administered | 7.25 number of anti-VEGF injections per eye | Standard Deviation 2.1 |
| Sham Radiation | Number of Anti-VEGF Injections Administered | 9.67 number of anti-VEGF injections per eye | Standard Deviation 3.5 |