Age-related Macular Degeneration
Conditions
Keywords
Age-related macular degeneration, Exudative age-related macular degeneration, Wet macular degeneration, Intravitreal injection, Proton beam irradiation, Lucentis, Ranibizumab
Brief summary
Because a possible synergism of radiation and inhibitors of vascular endothelial growth factor has been shown in cancer patients and patients with wet macular degeneration, this pilot study is being conducted to determine whether treating wet macular degeneration with a combination of Lucentis and proton beam irradiation is safe. Lucentis is an inhibitor of vascular endothelial growth factor which was recently FDA approved for treatment of wet macular degeneration. It appears to be the most effective therapy thus far for wet macular degeneration among all drugs FDA approved for this condition. If no major safety issues are associated with this combination therapy, a larger study will be conducted to determine whether this combination therapy is more effective than Lucentis monotherapy.
Detailed description
Five subjects diagnosed with wet macular degeneration will be treated with standard of care, i.e. intravitreal Lucentis injection monthly for the first four months and as needed thereafter. Within six weeks of the first Lucentis injection, the eye will also be treated with 24 Gy of proton beam divided into two fractions. Each subject will be followed for 2 yrs with monthly examination.
Interventions
DRUGProton beam irradiation and ranibizumab
ranibizumab 0.5mg intravitreal monthly x 4, then prn combined with low dose proton beam irradiation 24Gy (2 fractions, 24 hours apart) during the first month of study.
Sponsors
University of California, San Francisco
Genentech, Inc.
University of California, Davis
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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. * Hgb A1C \< 6 * Diagnosed with Age-related Macular Degeneration (ARMD) with active subfoveal choroidal neovascular membrane (CNVM), new or recurrent * Visual acuity 20/60 to 20/400 * Lesion size \< 12 Disc Area * Submacular hemorrhage less than 75% of total lesion * Submacular fibrosis less than 25% of total lesion * Candidate for intravitreal Lucentis
Exclusion criteria
* 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 * CNVM within 1 mm from the disc margin * Photodynamic Therapy (PDT) within 3 months * 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 * Systemic anticoagulation with coumadin * Head tremor or h/o claustrophobia precluding positioning for proton irradiation * Inability to maintain steady fixation with either eye * Diabetes mellitus requiring treatment * History of Malignancy treated within 5 years * Allergy to Fluorescein dye
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Ocular Adverse Events | 24 months | Any ocular adverse event identified by eye examination during the study follow-up will be recorded and determined for possible or probable relation to study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1. Change in BCVA From Baseline | 24 months | change in number of letter read correctly in study eye compared to the number of letters read correctly at baseline, i.e. BCVA (number of letters read correctly) at 24 months minus BCVA (number of letters read correctly) at baseline |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lucentis Combined With Proton Beam Proton beam irradiation and ranibizumab: ranibizumab 0.5mg intravitreal monthly x 4, then prn combined with low dose proton beam irradiation 24Gy (2 fractions, 24 hours apart) during the first month of study. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Lucentis Combined With Proton Beam |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Best corrected visual acuity | 0.58 logMAR best corrected visual acuity STANDARD_DEVIATION 0.26 |
| Optical coherence tomography central macular thickness | 335 microns STANDARD_DEVIATION 67 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Incidence and Severity of Ocular Adverse Events
Any ocular adverse event identified by eye examination during the study follow-up will be recorded and determined for possible or probable relation to study treatment.
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lucentis Combined With Proton Beam | Incidence and Severity of Ocular Adverse Events | 0 number of adverse events |
Secondary
1. Change in BCVA From Baseline
change in number of letter read correctly in study eye compared to the number of letters read correctly at baseline, i.e. BCVA (number of letters read correctly) at 24 months minus BCVA (number of letters read correctly) at baseline
Time frame: 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lucentis Combined With Proton Beam | 1. Change in BCVA From Baseline | 2.8 change in number of letters | Standard Deviation 26.4 |