RRR: Study of the Efficacy and Tolerability of Intravitreal Injections of Ranibizumab Compared to Intravitreal Injections of Ranibizumab Combined With Targeted Retinal Photocoagulation to Treat Radiation Retinopathy.

Sponsor
Greater Houston Retina Research (Other)
Overall Status
Completed
CT.gov ID
NCT02222610
Collaborator
Genentech, Inc. (Industry)
40
4
3
53.2
10
0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the tolerability and efficacy of ranibizumab treatment administered in subjects with radiation retinopathy

Condition or Disease Intervention/Treatment Phase
  • Drug: 0.5 mg ranibizumab
  • Procedure: Targeted Retinal Photocoagulation (TRP)
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
40 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Active-Controlled, Phase II Study of the Efficacy and Tolerability of Intravitreal Injections of Ranibizumab Compared to Intravitreal Injections of Ranibizumab Combined With Targeted Retinal Photocoagulation in Subjects With Radiation Retinopathy (RRR Study).
Actual Study Start Date :
Sep 23, 2014
Actual Primary Completion Date :
Mar 1, 2019
Actual Study Completion Date :
Mar 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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 spectral domain (SD)-optical coherence tomography (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.

Drug: 0.5 mg ranibizumab
Other Names:
  • Lucentis
  • Experimental: 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.

    Drug: 0.5 mg ranibizumab
    Other Names:
  • Lucentis
  • Procedure: Targeted Retinal Photocoagulation (TRP)
    TRP to areas of retinal ischemia

    Experimental: 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.

    Drug: 0.5 mg ranibizumab
    Other Names:
  • Lucentis
  • Procedure: Targeted Retinal Photocoagulation (TRP)
    TRP to areas of retinal ischemia

    Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    1. The Mean Number of Intravitreal Injections Required Per Subject Per Cohort. [104 weeks]

    2. Percentage of Subjects With Retinal Hemorrhage at 104 Weeks. [104 weeks]

    3. Percentage of Subjects With Intraretinal Exudates on Fundus Examination at Week 104. [104 weeks]

    4. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Texas Retina Associates Dallas Texas United States 75231
    2 Retina Consultants of Houston/The Medical Center Houston Texas United States 77030
    3 Retina Consultants of Houston Katy Texas United States 77494
    4 Retina Consultants of Houston The Woodlands Texas United States 77384

    Sponsors and Collaborators

    • Greater Houston Retina Research
    • Genentech, Inc.

    Investigators

    • Principal Investigator: Amy C Schefler, MD, Retina Consultants Houston

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Greater Houston Retina Research
    ClinicalTrials.gov Identifier:
    NCT02222610
    Other Study ID Numbers:
    • ML29236
    First Posted:
    Aug 21, 2014
    Last Update Posted:
    Mar 25, 2021
    Last Verified:
    Mar 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Greater Houston Retina Research
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Cohort A Cohort B Cohort C
    Arm/Group Description 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 Subject's receive monthly treatment of intravitreal (IVT) 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 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
    Period Title: Baseline to W48
    STARTED 8 16 16
    COMPLETED 8 14 15
    NOT COMPLETED 0 2 1
    Period Title: Baseline to W48
    STARTED 8 16 16
    COMPLETED 8 11 10
    NOT COMPLETED 0 5 6

    Baseline Characteristics

    Arm/Group Title Cohort A Cohort B Cohort C Total
    Arm/Group Description 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 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 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 Total of all reporting groups
    Overall Participants 8 16 16 40
    Overall Eyes 8 16 16 40
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    66.125
    54.813
    60.438
    57
    Sex: Female, Male (Count of Participants)
    Female
    5
    62.5%
    6
    37.5%
    5
    31.3%
    16
    40%
    Male
    3
    37.5%
    10
    62.5%
    11
    68.8%
    24
    60%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    1
    6.3%
    1
    2.5%
    Not Hispanic or Latino
    8
    100%
    16
    100%
    15
    93.8%
    39
    97.5%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    1
    6.3%
    0
    0%
    1
    2.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    8
    100%
    15
    93.8%
    16
    100%
    39
    97.5%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    8
    100%
    16
    100%
    16
    100%
    40
    100%
    Best-Corrected Visual Acuity (letters) [Mean (Full Range) ]
    Mean (Full Range) [letters]
    60.875
    55.813
    55.375
    56.7

    Outcome Measures

    1. Primary Outcome
    Title Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity at 104 Weeks From Day 0.
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Subjects analyzed only include those that completed the W104 visit.
    Arm/Group Title Cohort A Cohort B Cohort C
    Arm/Group Description 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 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 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
    Measure Participants 8 11 10
    Mean (Standard Deviation) [letters]
    -1.9
    (7.4)
    -3.9
    (16.5)
    1.3
    (11.8)
    2. Secondary Outcome
    Title The Mean Number of Intravitreal Injections Required Per Subject Per Cohort.
    Description
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort A Cohort B Cohort C
    Arm/Group Description 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 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 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
    Measure Participants 8 16 16
    Mean (Full Range) [injections]
    22.2
    18.5
    16.1
    3. Secondary Outcome
    Title Percentage of Subjects With Retinal Hemorrhage at 104 Weeks.
    Description
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort A Cohort B Cohort C
    Arm/Group Description 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 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 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
    Measure Participants 8 16 16
    Count of Participants [Participants]
    1
    12.5%
    0
    0%
    3
    18.8%
    4. Secondary Outcome
    Title Percentage of Subjects With Intraretinal Exudates on Fundus Examination at Week 104.
    Description
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort A Cohort B Cohort C
    Arm/Group Description 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 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 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
    Measure Participants 8 16 16
    Count of Participants [Participants]
    1
    12.5%
    2
    12.5%
    5
    31.3%
    5. Secondary Outcome
    Title Mean Change in Central Mean Thickness According to Spectral-domain Optical Coherence Tomography at Week 104 Compared to Baseline.
    Description 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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort A Cohort B Cohort C
    Arm/Group Description 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 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 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
    Measure Participants 8 16 16
    Mean (Standard Deviation) [micrometers]
    -8.5
    (216.7)
    -87
    (174.8)
    -74.6
    (176.7)

    Adverse Events

    Time Frame Baseline through 104 weeks
    Adverse Event Reporting Description
    Arm/Group Title Cohort A Cohort B Cohort C
    Arm/Group Description 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 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 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
    All Cause Mortality
    Cohort A Cohort B Cohort C
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/8 (0%) 0/16 (0%) 1/16 (6.3%)
    Serious Adverse Events
    Cohort A Cohort B Cohort C
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/8 (12.5%) 2/16 (12.5%) 5/16 (31.3%)
    Cardiac disorders
    Acute Chronic Diastolic Heart Failure 0/8 (0%) 0 0/16 (0%) 0 1/16 (6.3%) 1
    Chronic Atrial Fibrillation 0/8 (0%) 0 0/16 (0%) 0 1/16 (6.3%) 1
    Worsening of Hypertension 0/8 (0%) 0 0/16 (0%) 0 2/16 (12.5%) 2
    Endocrine disorders
    Pancreatitis 0/8 (0%) 0 0/16 (0%) 0 1/16 (6.3%) 1
    Eye disorders
    Central Retinal Artery Occlusion 0/8 (0%) 0 0/16 (0%) 0 1/16 (6.3%) 1
    Recurrence of Choroidal Melanoma 0/8 (0%) 0 1/16 (6.3%) 1 1/16 (6.3%) 1
    Metastatic Uveal Melanom 1/8 (12.5%) 1 1/16 (6.3%) 1 0/16 (0%) 0
    Musculoskeletal and connective tissue disorders
    Broken Wrist 0/8 (0%) 0 0/16 (0%) 0 1/16 (6.3%) 1
    Renal and urinary disorders
    Acute Chronic Renal Failure 0/8 (0%) 0 0/16 (0%) 0 1/16 (6.3%) 1
    Other (Not Including Serious) Adverse Events
    Cohort A Cohort B Cohort C
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/8 (37.5%) 7/16 (43.8%) 6/16 (37.5%)
    Eye disorders
    Corneal Abrasion 0/8 (0%) 0 0/16 (0%) 0 1/16 (6.3%) 1
    Dry Eyes 0/8 (0%) 0 0/16 (0%) 0 1/16 (6.3%) 1
    Increased Cup-to-Disc Rratio 0/8 (0%) 0 2/16 (12.5%) 2 0/16 (0%) 0
    Ocular Irritation 0/8 (0%) 0 0/16 (0%) 0 1/16 (6.3%) 1
    Ocular Pain 0/8 (0%) 0 0/16 (0%) 0 1/16 (6.3%) 2
    Posterior Capsular Opacification 0/8 (0%) 0 1/16 (6.3%) 1 2/16 (12.5%) 3
    Posterior Vitreous Detachment 1/8 (12.5%) 1 3/16 (18.8%) 3 1/16 (6.3%) 1
    Subconjunctival Hemorrhage 1/8 (12.5%) 1 0/16 (0%) 0 2/16 (12.5%) 2
    Worsening of Cataracts 2/8 (25%) 2 5/16 (31.3%) 6 3/16 (18.8%) 3

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Amy C. Schefler
    Organization Retina Consultants of Texas
    Phone (713) 524-3434
    Email acsmd@retinaconsultantstexas.com
    Responsible Party:
    Greater Houston Retina Research
    ClinicalTrials.gov Identifier:
    NCT02222610
    Other Study ID Numbers:
    • ML29236
    First Posted:
    Aug 21, 2014
    Last Update Posted:
    Mar 25, 2021
    Last Verified:
    Mar 1, 2021