Radiation Retinopathy
Conditions
Keywords
Radiation Retinopathy
Brief summary
The purpose of this study is to assess the tolerability and efficacy of ranibizumab treatment administered in subjects with radiation retinopathy
Detailed description
RRR is a phase II, randomized, multicenter, clinical study to assess the tolerability and efficacy of ranibizumab treatment administered in subjects with radiation retinopathy. Subjects will be randomized into one of 3 arms; intravitreal (IVT) monthly vs. ranibizumab treatment administered IVT monthly combined with peripheral targeted photocoagulation vs. ranibizumab treatment administered IVT for three months followed by as needed treatment of ranibizumab combined with peripheral targeted photocoagulation over 48 weeks. From week 52 to week 101, all 3 treatment arms will employ a treat and extend protocol for IVT ranibizumab treatment.
Interventions
PROCEDURETargeted Retinal Photocoagulation (TRP)
TRP to areas of retinal ischemia
Sponsors
Genentech, Inc.
Greater Houston Retina Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects will be eligible to participate 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 \> 18 years * Active radiation retinopathy resulting from any form of radiation treatment performed within the last 3 years. Radiation retinopathy is defined as any of the following: retinal hemorrhages, exudates, edema, and/or neovascularization, not attributable to other causes. * Best Corrected Visual Acuity (BCVA) of 20/25-20/400 in the study eye
Exclusion criteria
Subjects who meet any of the following criteria will be excluded from this study: * Pregnancy (verified by positive pregnancy test) or lactation * Premenopausal women not using adequate methods of contraception. The following are considered effective means of contraception: surgical sterilization, use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an intrauterine device (IUD), or contraceptive hormone implant or patch. * Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated. * Participation in any other simultaneous medical investigation or trial * Previous participation in any studies involving investigational drugs within 30 days before Day 0 (excluding vitamins and minerals). * History of allergy fluorescein, not amenable to treatment * Previous intravitreal treatment with any anti-vascular endothelial growth factor (VEGF) drug within 60 days of Day 0 * Previous intravitreal or subconjunctival treatment with cortical steroids within 90 days of Day 0 * History of vitrectomy * History of treatment with more than one form of radiation to the eye (e.g. proton beam therapy and plaque therapy). * Subjects who have more than 7 disc diameters of ischemia in the central macula that would hinder visual acuity improvement * History of panretinal photocoagulation treatment in the study eye. * Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed * Any concurrent intraocular condition in the study eye that, in the opinion of the investigator, could: * Require medical or surgical intervention during the 12 month study period to prevent or treat visual loss that might result from that condition. * Contribute to loss of at least 2 Snellen equivalent lines of BCVA over the 12-month study period, if allowed to progress untreated. * Active intraocular inflammation (grade 2+ or above) in the study eye * Current vitreous hemorrhage in the study eye * History of rhegmatogenous retinal detachment or macular hole (stage 3 or 4) in the study eye. * Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye. * Aphakia or absence of the posterior capsule in the study eye. * Intraocular surgery (including cataract surgery) in the study eye within 2 months preceding Day 0. * Uncontrolled glaucoma in the study eye (defined as intraocular pressure (IOP) \> 30 mmHg despite treatment with anti-glaucoma medication). * History of glaucoma-filtering surgery in the study eye * History of corneal transplant in the study eye * Uncontrolled blood pressure (defined as systolic and/or diastolic \> 180/110 mmHg while subject is seated). If the subject's initial reading exceeds these values, a second reading may be taken at least 30 minutes later. If the subject requires antihypertensive medication, the subject can become eligible if medication is taken continuously for at least 14 days prior to Day 0 and blood pressure is less that 180/110 mmHg. * New diagnosis of atrial fibrillation not managed by subject's primary care physician or cardiologist within 3 months of Day 0. * History of stroke within the last 3 months of Day 0. * History of myocardial infarction within 3 months of Day 0. * History of other disease, metabolic dysfunction, or physical examination finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or renders the subject at high risk for treatment complications. * Current treatment for active systemic infection * Active malignancy other than uveal melanoma * Presence of metastases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity at 104 Weeks From Day 0. | 104 weeks | Early Treatment Diabetic Retinopathy Study (ETDRS) Best-Corrected Visual Acuity (BCVA) utilizes the ETDRS visual acuity chart to measure vision in clinical trials. Standard unit of measure is the number of letters subjects are able to read on the chart. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Mean Number of Intravitreal Injections Required Per Subject Per Cohort. | 104 weeks | — |
| Percentage of Subjects With Retinal Hemorrhage at 104 Weeks. | 104 weeks | — |
| Percentage of Subjects With Intraretinal Exudates on Fundus Examination at Week 104. | 104 weeks | — |
| Mean Change in Central Mean Thickness According to Spectral-domain Optical Coherence Tomography at Week 104 Compared to Baseline. | 104 weeks | Spectral-domain optical coherence tomography (SD-OCT) is a common imaging modality used to visualize the layers of the macula. Central mean thickness (CMT) is the length in microns from the internal limiting membrane to Bruch's membrane. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A Subject's will receive monthly treatment of an intravitreal injection of 0.5 mg ranibizumab for 48 weeks.
Starting at week 52, subject's will enter a treat & extend regime, if a subject achieves a dry macula. For a macula to be considered dry persistent or recurrent fluid must be resolved on SD-OCT. The interval between injections will not exceed 12 weeks. After a subject is extended beyond 4-weeks & develops recurrent disease activity, the eye is treated & the treatment interval for the next visit is reduced by 1 week, compared to the previous treatment interval. The interval between treatments will be reduced by 1-week intervals until a dry macula is again established. Once a dry macula is again achieved, the interval between visits will be extended by 1-week intervals again.
0.5 mg ranibizumab | 8 |
| Cohort A Subject's will receive monthly treatment of an intravitreal injection of 0.5 mg ranibizumab for 48 weeks.
Starting at week 52, subject's will enter a treat & extend regime, if a subject achieves a dry macula. For a macula to be considered dry persistent or recurrent fluid must be resolved on SD-OCT. The interval between injections will not exceed 12 weeks. After a subject is extended beyond 4-weeks & develops recurrent disease activity, the eye is treated & the treatment interval for the next visit is reduced by 1 week, compared to the previous treatment interval. The interval between treatments will be reduced by 1-week intervals until a dry macula is again established. Once a dry macula is again achieved, the interval between visits will be extended by 1-week intervals again.
0.5 mg ranibizumab | 8 |
| Cohort B Subject's receive monthly treatment of IVT of 0.5 mg ranibizumab for 48 weeks. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia based on 120° or greater wide field angiography. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks & 24 weeks & will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.
Starting at week 52, subject's will enter a treat & extend regime as described in cohort A.
0.5 mg ranibizumab
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia | 16 |
| Cohort B Subject's receive monthly treatment of IVT of 0.5 mg ranibizumab for 48 weeks. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia based on 120° or greater wide field angiography. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks & 24 weeks & will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.
Starting at week 52, subject's will enter a treat & extend regime as described in cohort A.
0.5 mg ranibizumab
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia | 16 |
| Cohort C Subject's will receive 3 consecutive monthly doses of IVT 0.5 mg ranibizumab followed by PRN treatment with 0.5 mg ranibizumab intravitreal injection. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks & 24 weeks & will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.
Starting at week 52, subject's will enter a treat & extend regime as described in cohort A.
0.5 mg ranibizumab
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia | 16 |
| Cohort C Subject's will receive 3 consecutive monthly doses of IVT 0.5 mg ranibizumab followed by PRN treatment with 0.5 mg ranibizumab intravitreal injection. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks & 24 weeks & will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.
Starting at week 52, subject's will enter a treat & extend regime as described in cohort A.
0.5 mg ranibizumab
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia | 16 |
| Total | 80 |
Baseline characteristics
| Characteristic | Cohort A | Cohort B | Cohort C | Total |
|---|---|---|---|---|
| Age, Continuous | 66.125 years | 54.813 years | 60.438 years | 57 years |
| Best-Corrected Visual Acuity | 60.875 letters | 55.813 letters | 55.375 letters | 56.7 letters |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 16 Participants | 15 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 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 | 8 Participants | 15 Participants | 16 Participants | 39 Participants |
| Region of Enrollment United States | 8 participants | 16 participants | 16 participants | 40 participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 5 Participants | 16 Participants |
| Sex: Female, Male Male | 3 Participants | 10 Participants | 11 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 16 | 1 / 16 |
| other Total, other adverse events | 3 / 8 | 7 / 16 | 6 / 16 |
| serious Total, serious adverse events | 1 / 8 | 2 / 16 | 5 / 16 |
Outcome results
Primary
Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity at 104 Weeks From Day 0.
Early Treatment Diabetic Retinopathy Study (ETDRS) Best-Corrected Visual Acuity (BCVA) utilizes the ETDRS visual acuity chart to measure vision in clinical trials. Standard unit of measure is the number of letters subjects are able to read on the chart.
Time frame: 104 weeks
Population: Subjects analyzed only include those that completed the W104 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A | Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity at 104 Weeks From Day 0. | -1.9 letters | Standard Deviation 7.4 |
| Cohort B | Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity at 104 Weeks From Day 0. | -3.9 letters | Standard Deviation 16.5 |
| Cohort C | Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity at 104 Weeks From Day 0. | 1.3 letters | Standard Deviation 11.8 |
Secondary
Mean Change in Central Mean Thickness According to Spectral-domain Optical Coherence Tomography at Week 104 Compared to Baseline.
Spectral-domain optical coherence tomography (SD-OCT) is a common imaging modality used to visualize the layers of the macula. Central mean thickness (CMT) is the length in microns from the internal limiting membrane to Bruch's membrane.
Time frame: 104 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A | Mean Change in Central Mean Thickness According to Spectral-domain Optical Coherence Tomography at Week 104 Compared to Baseline. | -8.5 micrometers | Standard Deviation 216.7 |
| Cohort B | Mean Change in Central Mean Thickness According to Spectral-domain Optical Coherence Tomography at Week 104 Compared to Baseline. | -87 micrometers | Standard Deviation 174.8 |
| Cohort C | Mean Change in Central Mean Thickness According to Spectral-domain Optical Coherence Tomography at Week 104 Compared to Baseline. | -74.6 micrometers | Standard Deviation 176.7 |
Secondary
Percentage of Subjects With Intraretinal Exudates on Fundus Examination at Week 104.
Time frame: 104 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A | Percentage of Subjects With Intraretinal Exudates on Fundus Examination at Week 104. | 1 Participants |
| Cohort B | Percentage of Subjects With Intraretinal Exudates on Fundus Examination at Week 104. | 2 Participants |
| Cohort C | Percentage of Subjects With Intraretinal Exudates on Fundus Examination at Week 104. | 5 Participants |
Secondary
Percentage of Subjects With Retinal Hemorrhage at 104 Weeks.
Time frame: 104 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A | Percentage of Subjects With Retinal Hemorrhage at 104 Weeks. | 1 Participants |
| Cohort B | Percentage of Subjects With Retinal Hemorrhage at 104 Weeks. | 0 Participants |
| Cohort C | Percentage of Subjects With Retinal Hemorrhage at 104 Weeks. | 3 Participants |
Secondary
The Mean Number of Intravitreal Injections Required Per Subject Per Cohort.
Time frame: 104 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort A | The Mean Number of Intravitreal Injections Required Per Subject Per Cohort. | 22.2 injections |
| Cohort B | The Mean Number of Intravitreal Injections Required Per Subject Per Cohort. | 18.5 injections |
| Cohort C | The Mean Number of Intravitreal Injections Required Per Subject Per Cohort. | 16.1 injections |