Retinal Vein Occlusion
Conditions
Keywords
RVO, BRVO, CRVO, Vein occlusion
Brief summary
The primary Objective of this study is to evaluate the safety and tolerability of intraocular injections of 0.5mg or 2.0mg of ranibizumab in patients with macular edema due to retinal vein occlusion.
Detailed description
The secondary objectives are to assess the efficacy of 0.5mg versus 2.0mg of monthly ranibizumab injections in patients with macular edema due to retinal vein occlusion between baseline and month 6. At week 24, patients will be re-randomized to receive pro re nata (prn) ranibizumab+laser photocoagulation versus ranibizumab alone and the efficacy of both treatment options will be compared. Treatment efficacy will be assessed by comparing changes in best corrected visual acuity (BCVA) and central subfiled thickness (CST) between the treatment groups.
Interventions
DRUGRanibizumab 0.5mg (monthly)
Branch retinal vein occlusion- Intravitreal injection of 0.5mg ranibizumab alone
DRUGRanibizumab 2.0mg (monthly)
DRUGPro re nata (prn) ranibizumab
PROCEDUREPro re nata (prn) Laser photocoagulation
Sponsors
Genentech, Inc.
Peter A Campochiaro, MD
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
* Signed informed consent and authorization of use and disclosure of protected health information * Age equal to or greater than 18 years * Diagnosis of macular edema due to central or branch retinal vein occlusion * Foveal thickness of equal to or greater than 250 mm, as assessed by OCT * Best corrected visual acuity score in the study eye of 20/40 to 20/400 inclusive (Snellen equivalents using the ETDRS protocol at a distance of 4 meters). Only one eye will be treated in the study. If both eyes are eligible, the investigator will select the eye to be enrolled. * In the opinion of the investigator, decreased vision in the study eye is due to foveal thickening from vein occlusion and not from other obvious causes of decreased vision
Exclusion criteria
* Scatter laser photocoagulation or macular photocoagulation within 3 months of study entry in the study eye * Intraocular surgery in the study eye within 3 months of study entry * Use of intraocular or periocular injection of steroids in the study eye (e.g., triamcinolone) within 4 months of study entry * Previous use of an anti-VEGF drug within 3 months of study entry * Cataract surgery in the study eye within 3 months of study entry; Yttrium-Aluminum-Garnet (YAG) laser capsulotomy within 1 month of study entry; or any other intraocular surgery within 3 months preceding Day 0. * History of vitreoretinal surgery in the study eye within 3 months of study entry * Uncontrolled glaucoma (defined as intraocular pressure ³30 mm Hg despite treatment with anti-glaucoma medications) * History of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 3 months of study enrollment. * Pregnancy (positive pregnancy test) or lactation * Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch. * Have the presence of active malignancy, including lymphoproliferative disorders. Subjects with a history of fully resolved basal or squamous cell skin cancer may be enrolled. * Any condition that the investigator believes would pose a significant hazard to the subject if investigational therapy were initiated. * History of allergy to humanized antibodies or any component of the ranibizumab formulation * Inability to comply with study or followup procedures * Participation in another simultaneous medical investigation or trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and Severity of Ocular and Non-ocular Adverse Events. | 36 months |
Secondary
| Measure | Time frame |
|---|---|
| Mean Change From Baseline to Month 6 in Best Corrected Visual Acuity in Patients Treated With 0.5mg Versus 2.0mg of Ranibizumab | Baseline to month 6 |
| Mean Change From Month 6 to Month 36 in Best Corrected Visual Acuity in Patients Treated With Prn Ranibizumab+Laser Photocoagulation Versus Prn Ranibizumab Alone. | Month 6- Month 36 |
| Mean Change From Baseline to Month 6 in Central Subfield Thickness in Patients Treated With 0.5mg Versus 2.0mg of Ranibizumab | Baseline to month 6 |
| Mean Change From Month 6 to Month 36 in Central Subfield Thickness in Patients Treated With Prn Ranibizumab+Laser Photocoagulation Versus Prn Ranibizumab Alone. | Month 6- Month 36 |
Countries
United States
Participant flow
Recruitment details
Eighty-one patients with retinal vein occlusion were enrolled at a single center (The Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore,MD).
Participants by arm
| Arm | Count |
|---|---|
| BRVO- Ranibizumab 0.5mg Alone Branch retinal vein occlusion patients randomized to this group will receive 0.5mg of ranibizumab alone as per protocol without laser photocoagulation.
BRVO -Ranibizumab 0.5mg alone: Branch retinal vein occlusion- Intravitreal injection of 0.5mg ranibizumab alone | 22 |
| BRVO- Ranibizumab 2.0mg Alone Branch retinal vein occlusion patients randomized to this group will receive 2.0mg of ranibizumab alone as per protocol without laser photocoagulation.
BRVO- Ranibizumab 2.0 mg alone: Branch retinal vein occlusion- Intravitreal injection of 2.0mg ranibizumab alone | 20 |
| CRVO- Ranibizumab 0.5mg Alone Central retinal vein occlusion patients randomized to this group will receive 0.5mg of ranibizumab alone as per protocol without laser photocoagulation
CRVO -Ranibizumab 0.5mg alone: Central retinal vein occlusion- Intravitreal injection of 0.5mg ranibizumab alone | 19 |
| CRVO- Ranibizumab 2.0mg Alone Central retinal vein occlusion patients randomized to this group will receive 2.0mg of ranibizumab alone as per protocol without laser photocoagulation.
CRVO- Ranibizumab 2.0 mg alone: Central retinal vein occlusion- Intravitreal injection of 2.0mg ranibizumab alone | 20 |
| Total | 81 |
Baseline characteristics
| Characteristic | BRVO- Ranibizumab 0.5mg Alone | BRVO- Ranibizumab 2.0mg Alone | CRVO- Ranibizumab 0.5mg Alone | CRVO- Ranibizumab 2.0mg Alone | Total |
|---|---|---|---|---|---|
| Age, Continuous | 66.6 years STANDARD_DEVIATION 2.2 | 69.3 years STANDARD_DEVIATION 1.8 | 59.0 years STANDARD_DEVIATION 2.9 | 64.4 years STANDARD_DEVIATION 2.9 | 64.7 years STANDARD_DEVIATION 2.5 |
| Sex: Female, Male Female | 13 Participants | 7 Participants | 9 Participants | 9 Participants | 38 Participants |
| Sex: Female, Male Male | 9 Participants | 13 Participants | 10 Participants | 11 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 37 / 42 | 35 / 39 |
| serious Total, serious adverse events | 17 / 42 | 12 / 39 |
Outcome results
Primary
Incidence and Severity of Ocular and Non-ocular Adverse Events.
Time frame: 36 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BRVO | Incidence and Severity of Ocular and Non-ocular Adverse Events. | Patients with Serious Adverse Events | 17 participants |
| BRVO | Incidence and Severity of Ocular and Non-ocular Adverse Events. | Patient with (non serious) adverse events | 37 participants |
| CRVO | Incidence and Severity of Ocular and Non-ocular Adverse Events. | Patients with Serious Adverse Events | 12 participants |
| CRVO | Incidence and Severity of Ocular and Non-ocular Adverse Events. | Patient with (non serious) adverse events | 35 participants |
Secondary
Mean Change From Baseline to Month 6 in Best Corrected Visual Acuity in Patients Treated With 0.5mg Versus 2.0mg of Ranibizumab
Time frame: Baseline to month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BRVO | Mean Change From Baseline to Month 6 in Best Corrected Visual Acuity in Patients Treated With 0.5mg Versus 2.0mg of Ranibizumab | 12.1 Letters | Standard Error 2.9 |
| CRVO | Mean Change From Baseline to Month 6 in Best Corrected Visual Acuity in Patients Treated With 0.5mg Versus 2.0mg of Ranibizumab | 14.6 Letters | Standard Error 2.3 |
| CRVO- Ranibizumab 0.5mg Alone | Mean Change From Baseline to Month 6 in Best Corrected Visual Acuity in Patients Treated With 0.5mg Versus 2.0mg of Ranibizumab | 15.5 Letters | Standard Error 2.4 |
| CRVO- Ranibizumab 2.0mg Alone | Mean Change From Baseline to Month 6 in Best Corrected Visual Acuity in Patients Treated With 0.5mg Versus 2.0mg of Ranibizumab | 15.8 Letters | Standard Error 2.4 |
Secondary
Mean Change From Baseline to Month 6 in Central Subfield Thickness in Patients Treated With 0.5mg Versus 2.0mg of Ranibizumab
Time frame: Baseline to month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BRVO | Mean Change From Baseline to Month 6 in Central Subfield Thickness in Patients Treated With 0.5mg Versus 2.0mg of Ranibizumab | -203.3 microns | Standard Error 41 |
| CRVO | Mean Change From Baseline to Month 6 in Central Subfield Thickness in Patients Treated With 0.5mg Versus 2.0mg of Ranibizumab | -292.1 microns | Standard Error 55 |
| CRVO- Ranibizumab 0.5mg Alone | Mean Change From Baseline to Month 6 in Central Subfield Thickness in Patients Treated With 0.5mg Versus 2.0mg of Ranibizumab | -253.5 microns | Standard Error 43 |
| CRVO- Ranibizumab 2.0mg Alone | Mean Change From Baseline to Month 6 in Central Subfield Thickness in Patients Treated With 0.5mg Versus 2.0mg of Ranibizumab | -396.1 microns | Standard Error 48.1 |
Secondary
Mean Change From Month 6 to Month 36 in Best Corrected Visual Acuity in Patients Treated With Prn Ranibizumab+Laser Photocoagulation Versus Prn Ranibizumab Alone.
Time frame: Month 6- Month 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BRVO | Mean Change From Month 6 to Month 36 in Best Corrected Visual Acuity in Patients Treated With Prn Ranibizumab+Laser Photocoagulation Versus Prn Ranibizumab Alone. | 3.1 Letters | Standard Error 3.3 |
| CRVO | Mean Change From Month 6 to Month 36 in Best Corrected Visual Acuity in Patients Treated With Prn Ranibizumab+Laser Photocoagulation Versus Prn Ranibizumab Alone. | -2.6 Letters | Standard Error 2.2 |
| CRVO- Ranibizumab 0.5mg Alone | Mean Change From Month 6 to Month 36 in Best Corrected Visual Acuity in Patients Treated With Prn Ranibizumab+Laser Photocoagulation Versus Prn Ranibizumab Alone. | -6.7 Letters | Standard Error 3.7 |
| CRVO- Ranibizumab 2.0mg Alone | Mean Change From Month 6 to Month 36 in Best Corrected Visual Acuity in Patients Treated With Prn Ranibizumab+Laser Photocoagulation Versus Prn Ranibizumab Alone. | 0.4 Letters | Standard Error 4.3 |
Secondary
Mean Change From Month 6 to Month 36 in Central Subfield Thickness in Patients Treated With Prn Ranibizumab+Laser Photocoagulation Versus Prn Ranibizumab Alone.
Time frame: Month 6- Month 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BRVO | Mean Change From Month 6 to Month 36 in Central Subfield Thickness in Patients Treated With Prn Ranibizumab+Laser Photocoagulation Versus Prn Ranibizumab Alone. | -3.2 microns | Standard Error 54.7 |
| CRVO | Mean Change From Month 6 to Month 36 in Central Subfield Thickness in Patients Treated With Prn Ranibizumab+Laser Photocoagulation Versus Prn Ranibizumab Alone. | 36.6 microns | Standard Error 29.2 |
| CRVO- Ranibizumab 0.5mg Alone | Mean Change From Month 6 to Month 36 in Central Subfield Thickness in Patients Treated With Prn Ranibizumab+Laser Photocoagulation Versus Prn Ranibizumab Alone. | 19.1 microns | Standard Error 50.3 |
| CRVO- Ranibizumab 2.0mg Alone | Mean Change From Month 6 to Month 36 in Central Subfield Thickness in Patients Treated With Prn Ranibizumab+Laser Photocoagulation Versus Prn Ranibizumab Alone. | 58.8 microns | Standard Error 38.5 |