Age-Related Macular Degeneration, AMD, Eye Diseases, Macular Degeneration, Retinal Diseases, Wet Age-Related Macular Degeneration, Wet AMD
Conditions
Keywords
Oraya, Oraya Therapeutics, Inc., low voltage stereotactic radiotherapy, radiotherapy, IRay, Ranibizumab, Lucentis, AMD, Macular Degeneration, xray, radiation, x ray, external beam radiation, radiosurgery
Brief summary
The purpose of this study is to confirm the safety and establish the effectiveness of two doses from the IRay System for the treatment of wet AMD.
Detailed description
The purpose of this study is to confirm the safety of low voltage external beam radiotherapy using the IRay System at two dose levels for the treatment of CNV secondary to neovascular AMD and to determine if the IRay System is effective in sparing the number of Lucentis injections during the first 12 months.
Interventions
DEVICEIRay
Low voltage stereotactic radiotherapy system
Sponsors
Oraya Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have neovascular AMD diagnosed within the previous 3 years, have received at least 3 injections with Lucentis® or Avastin® within the previous year and have the need for treatment with anti-VEGF therapy due to increased fluid or persistent cysts on OCT, or leakage on FA. * Patients must have a total lesion size of \<12 disc areas and a CNV lesion with the greatest linear dimension of \<6 mm, but not greater than 3 mm from the center of the fovea to the furthest point on the lesion perimeter. * The distance from the center of the fovea to the nearest edge of the optic disc should be not less than 3 mm. * Patients must Patient must be at least 50 years of age. * Women must be post-menopausal ≥1 year or surgically sterilized, or a pregnancy screen must be performed prior to the study and a reliable form of contraception approved by the investigator must be maintained during the study. * Patient must have best corrected visual acuity of 75 to 25 letters in the study eye and at least 20 letters in the fellow eye.
Exclusion criteria
* CNV due to causes other than AMD, including ocular histoplasmosis syndrome, angioid streaks, multifocal choroiditis, choroidal rupture, or pathologic myopia (spherical equivalent ≥ -8 diopters). * An axial length of ≤20 mm or ≥26 mm. * Previously diagnosed with Diabetes Mellitus and/or an HbA1c of \>6.5%, and with retinal findings consistent with diabetic retinopathy. * Prior or concurrent therapies for age related macular degeneration including submacular surgery, subfoveal thermal laser photocoagulation (with or without photographic evidence), transpupillary thermotherapy (TTT), ocular photodynamic therapy, radiation therapy to the head or neck in the study eye. * Previous posterior vitrectomy, or any surgery in the study eye within 6 months or YAG capsulotomy within 3 months prior to the screening visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Lucentis® Injections Up To And Including Week 52 | During the first 52 weeks. |
Secondary
| Measure | Time frame |
|---|---|
| Percentage (Pct.) of Patients (Pts.) Losing < 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Weeks 12, 28 and 52. |
| Percentage (Pct.) of Patients (Pts.) Gaining ≥ 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Weeks 12, 28 and 52. |
| Percentage (Pct.) of Patients (Pts.) Gaining ≥ 0 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Weeks 12, 28 and 52. |
| Change in Mean Visual Acuity (VA) | Weeks 12, 28, 52 and 104. |
| Total Number (No.) of Lucentis® Injections (Inject.) During The First 12, 28, and 104 Weeks. | Week 12, 28, and 104 |
| Mean Change in Choroidal Neovascularization (CNV) as % of Lesion on Fluorescein Angiography (FA) From Baseline to Week 52 | Week 52 |
| Time From Mandatory Injection at Day 0 to the First PRN Injection. | 52 Weeks |
Countries
Austria, Czechia, Germany, Italy, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 16 Gy IRay 16 Gy IRay + PRN Lucentis®
IRay: Low voltage stereotactic radiotherapy system | 75 |
| 24 Gy IRay 24 Gy IRay + PRN Lucentis®
IRay: Low voltage stereotactic radiotherapy system | 75 |
| Sham IRay Sham 16 or 24 Gy IRay + PRN Lucentis®
IRay: Low voltage stereotactic radiotherapy system | 80 |
| Total | 230 |
Baseline characteristics
| Characteristic | 16 Gy IRay | 24 Gy IRay | Sham IRay | Total |
|---|---|---|---|---|
| Age, Customized Age | 73.35 years STANDARD_DEVIATION 7.18 | 73.77 years STANDARD_DEVIATION 8.26 | 73.45 years STANDARD_DEVIATION 7.14 | 73.52 years STANDARD_DEVIATION 7.51 |
| Region of Enrollment Austria | 4 participants | 20 participants | 4 participants | 28 participants |
| Region of Enrollment Czech Republic | 48 participants | 29 participants | 47 participants | 124 participants |
| Region of Enrollment Germany | 6 participants | 7 participants | 10 participants | 23 participants |
| Region of Enrollment Italy | 3 participants | 1 participants | 2 participants | 6 participants |
| Region of Enrollment United Kingdom | 14 participants | 18 participants | 17 participants | 49 participants |
| Sex: Female, Male Female | 43 Participants | 48 Participants | 49 Participants | 140 Participants |
| Sex: Female, Male Male | 32 Participants | 27 Participants | 31 Participants | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 75 | 23 / 75 | 24 / 80 |
| serious Total, serious adverse events | 12 / 75 | 8 / 75 | 7 / 80 |
Outcome results
Primary
Number of Lucentis® Injections Up To And Including Week 52
Time frame: During the first 52 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 16 Gy IRay | Number of Lucentis® Injections Up To And Including Week 52 | 2.64 Injections | Standard Deviation 2.46 |
| 24 Gy IRay | Number of Lucentis® Injections Up To And Including Week 52 | 2.44 Injections | Standard Deviation 2.41 |
| Sham IRay | Number of Lucentis® Injections Up To And Including Week 52 | 3.73 Injections | Standard Deviation 2.58 |
Secondary
Change in Mean Visual Acuity (VA)
Time frame: Weeks 12, 28, 52 and 104.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 16 Gy IRay | Change in Mean Visual Acuity (VA) | Mean change in VA Week 52, n = 74, 72, 79 | -0.28 Letters | Standard Deviation 8.77 |
| 16 Gy IRay | Change in Mean Visual Acuity (VA) | Mean change in VA Week 28, n = 73, 73, 77 | -0.33 Letters | Standard Deviation 8.25 |
| 16 Gy IRay | Change in Mean Visual Acuity (VA) | Visual Acuity (VA) - Baseline | 57.91 Letters | Standard Deviation 12.72 |
| 16 Gy IRay | Change in Mean Visual Acuity (VA) | Mean change in VA Week 12, n = 73, 71, 78 | 0.86 Letters | Standard Deviation 5.68 |
| 16 Gy IRay | Change in Mean Visual Acuity (VA) | Mean change in VA Week 104, n = 68, 68, 73 | -10.03 Letters | Standard Deviation 16.45 |
| 24 Gy IRay | Change in Mean Visual Acuity (VA) | Mean change in VA Week 28, n = 73, 73, 77 | 2.04 Letters | Standard Deviation 8.58 |
| 24 Gy IRay | Change in Mean Visual Acuity (VA) | Visual Acuity (VA) - Baseline | 58.75 Letters | Standard Deviation 12.79 |
| 24 Gy IRay | Change in Mean Visual Acuity (VA) | Mean change in VA Week 12, n = 73, 71, 78 | 1.85 Letters | Standard Deviation 9.73 |
| 24 Gy IRay | Change in Mean Visual Acuity (VA) | Mean change in VA Week 52, n = 74, 72, 79 | 0.40 Letters | Standard Deviation 10.33 |
| 24 Gy IRay | Change in Mean Visual Acuity (VA) | Mean change in VA Week 104, n = 68, 68, 73 | -7.49 Letters | Standard Deviation 16.49 |
| Sham IRay | Change in Mean Visual Acuity (VA) | Mean change in VA Week 104, n = 68, 68, 73 | -6.71 Letters | Standard Deviation 17.08 |
| Sham IRay | Change in Mean Visual Acuity (VA) | Mean change in VA Week 52, n = 74, 72, 79 | -0.58 Letters | Standard Deviation 10.56 |
| Sham IRay | Change in Mean Visual Acuity (VA) | Visual Acuity (VA) - Baseline | 59.29 Letters | Standard Deviation 13.09 |
| Sham IRay | Change in Mean Visual Acuity (VA) | Mean change in VA Week 28, n = 73, 73, 77 | 1.42 Letters | Standard Deviation 7.91 |
| Sham IRay | Change in Mean Visual Acuity (VA) | Mean change in VA Week 12, n = 73, 71, 78 | 2.06 Letters | Standard Deviation 6.79 |
Secondary
Mean Change in Choroidal Neovascularization (CNV) as % of Lesion on Fluorescein Angiography (FA) From Baseline to Week 52
Time frame: Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 16 Gy IRay | Mean Change in Choroidal Neovascularization (CNV) as % of Lesion on Fluorescein Angiography (FA) From Baseline to Week 52 | -0.16 CNV as % of Lesion | Standard Deviation 0.33 |
| 24 Gy IRay | Mean Change in Choroidal Neovascularization (CNV) as % of Lesion on Fluorescein Angiography (FA) From Baseline to Week 52 | -0.18 CNV as % of Lesion | Standard Deviation 0.33 |
| Sham IRay | Mean Change in Choroidal Neovascularization (CNV) as % of Lesion on Fluorescein Angiography (FA) From Baseline to Week 52 | -0.10 CNV as % of Lesion | Standard Deviation 0.26 |
Secondary
Percentage (Pct.) of Patients (Pts.) Gaining ≥ 0 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.)
Time frame: Weeks 12, 28 and 52.
Population: Number of Participants Analyzed:~* Week 12: n = 73, 71, 78~* Week 28: n = 73, 73, 77~* Week 52: n = 74, 72, 79
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 16 Gy IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 0 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=0 Letters From Base. - W28 | 52 Percentage of Patients |
| 16 Gy IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 0 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=0 Letters From Base. - W12 | 60 Percentage of Patients |
| 16 Gy IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 0 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=0 Letters From Base. - W52 | 53 Percentage of Patients |
| 24 Gy IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 0 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=0 Letters From Base. - W28 | 62 Percentage of Patients |
| 24 Gy IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 0 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=0 Letters From Base. - W12 | 65 Percentage of Patients |
| 24 Gy IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 0 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=0 Letters From Base. - W52 | 57 Percentage of Patients |
| Sham IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 0 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=0 Letters From Base. - W12 | 74 Percentage of Patients |
| Sham IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 0 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=0 Letters From Base. - W52 | 57 Percentage of Patients |
| Sham IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 0 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=0 Letters From Base. - W28 | 64 Percentage of Patients |
Secondary
Percentage (Pct.) of Patients (Pts.) Gaining ≥ 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.)
Time frame: Weeks 12, 28 and 52.
Population: Number of Participants Analyzed:~* Week 12: n = 73, 71, 78~* Week 28: n = 73, 73, 77~* Week 52: n = 74, 72, 79
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 16 Gy IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=15 Letters from Base. -W28 | 4 Proportion of Patients |
| 16 Gy IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=15 Letters from Base. -W12 | 0 Proportion of Patients |
| 16 Gy IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=15 Letters from Base. -W52 | 4 Proportion of Patients |
| 24 Gy IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=15 Letters from Base. -W28 | 4 Proportion of Patients |
| 24 Gy IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=15 Letters from Base. -W12 | 6 Proportion of Patients |
| 24 Gy IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=15 Letters from Base. -W52 | 4 Proportion of Patients |
| Sham IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=15 Letters from Base. -W12 | 1 Proportion of Patients |
| Sham IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=15 Letters from Base. -W52 | 5 Proportion of Patients |
| Sham IRay | Percentage (Pct.) of Patients (Pts.) Gaining ≥ 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Gaining >=15 Letters from Base. -W28 | 3 Proportion of Patients |
Secondary
Percentage (Pct.) of Patients (Pts.) Losing < 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.)
Time frame: Weeks 12, 28 and 52.
Population: Number of Participants Analyzed:~* Week 12: n = 73, 71, 78~* Week 28: n = 73, 73, 77~* Week 52: n = 74, 72, 79
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 16 Gy IRay | Percentage (Pct.) of Patients (Pts.) Losing < 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Losing <15 Letters From Base. - W28 | 97 Percentage of Patients |
| 16 Gy IRay | Percentage (Pct.) of Patients (Pts.) Losing < 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Losing <15 Letters From Base. - W12 | 100 Percentage of Patients |
| 16 Gy IRay | Percentage (Pct.) of Patients (Pts.) Losing < 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Losing <15 Letters From Base. - W52 | 93 Percentage of Patients |
| 24 Gy IRay | Percentage (Pct.) of Patients (Pts.) Losing < 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Losing <15 Letters From Base. - W28 | 96 Percentage of Patients |
| 24 Gy IRay | Percentage (Pct.) of Patients (Pts.) Losing < 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Losing <15 Letters From Base. - W12 | 97 Percentage of Patients |
| 24 Gy IRay | Percentage (Pct.) of Patients (Pts.) Losing < 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Losing <15 Letters From Base. - W52 | 89 Percentage of Patients |
| Sham IRay | Percentage (Pct.) of Patients (Pts.) Losing < 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Losing <15 Letters From Base. - W12 | 97 Percentage of Patients |
| Sham IRay | Percentage (Pct.) of Patients (Pts.) Losing < 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Losing <15 Letters From Base. - W52 | 92 Percentage of Patients |
| Sham IRay | Percentage (Pct.) of Patients (Pts.) Losing < 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) | Pct. of Pts. Losing <15 Letters From Base. - W28 | 97 Percentage of Patients |
Secondary
Time From Mandatory Injection at Day 0 to the First PRN Injection.
Time frame: 52 Weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 16 Gy IRay | Time From Mandatory Injection at Day 0 to the First PRN Injection. | 16.29 Weeks |
| 24 Gy IRay | Time From Mandatory Injection at Day 0 to the First PRN Injection. | 16.71 Weeks |
| Sham IRay | Time From Mandatory Injection at Day 0 to the First PRN Injection. | 13.14 Weeks |
Secondary
Total Number (No.) of Lucentis® Injections (Inject.) During The First 12, 28, and 104 Weeks.
Time frame: Week 12, 28, and 104
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 16 Gy IRay | Total Number (No.) of Lucentis® Injections (Inject.) During The First 12, 28, and 104 Weeks. | No. of Injections - Week 28, n = 75,75,80 | 1.51 Number of Injections | Standard Deviation 1.35 |
| 16 Gy IRay | Total Number (No.) of Lucentis® Injections (Inject.) During The First 12, 28, and 104 Weeks. | Mean No. of Injections - Week 12, n = 75,75,80 | 0.57 Number of Injections | Standard Deviation 0.7 |
| 16 Gy IRay | Total Number (No.) of Lucentis® Injections (Inject.) During The First 12, 28, and 104 Weeks. | Mean No. of Injections - Week 104, n=75,75,80 | 4.48 Number of Injections | Standard Deviation 3.94 |
| 24 Gy IRay | Total Number (No.) of Lucentis® Injections (Inject.) During The First 12, 28, and 104 Weeks. | No. of Injections - Week 28, n = 75,75,80 | 1.28 Number of Injections | Standard Deviation 1.37 |
| 24 Gy IRay | Total Number (No.) of Lucentis® Injections (Inject.) During The First 12, 28, and 104 Weeks. | Mean No. of Injections - Week 12, n = 75,75,80 | 0.56 Number of Injections | Standard Deviation 0.74 |
| 24 Gy IRay | Total Number (No.) of Lucentis® Injections (Inject.) During The First 12, 28, and 104 Weeks. | Mean No. of Injections - Week 104, n=75,75,80 | 5.37 Number of Injections | Standard Deviation 4.57 |
| Sham IRay | Total Number (No.) of Lucentis® Injections (Inject.) During The First 12, 28, and 104 Weeks. | Mean No. of Injections - Week 12, n = 75,75,80 | 0.73 Number of Injections | Standard Deviation 0.78 |
| Sham IRay | Total Number (No.) of Lucentis® Injections (Inject.) During The First 12, 28, and 104 Weeks. | Mean No. of Injections - Week 104, n=75,75,80 | 6.61 Number of Injections | Standard Deviation 4.28 |
| Sham IRay | Total Number (No.) of Lucentis® Injections (Inject.) During The First 12, 28, and 104 Weeks. | No. of Injections - Week 28, n = 75,75,80 | 1.83 Number of Injections | Standard Deviation 1.41 |