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.

NCT ID: NCT02222610

Last Updated: 2021-03-25

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-09-23

Study Completion Date

2019-03-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Radiation Retinopathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

0.5 mg ranibizumab

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

0.5 mg ranibizumab

Intervention Type DRUG

Targeted Retinal Photocoagulation (TRP)

Intervention Type PROCEDURE

TRP to areas of retinal ischemia

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.

Group Type EXPERIMENTAL

0.5 mg ranibizumab

Intervention Type DRUG

Targeted Retinal Photocoagulation (TRP)

Intervention Type PROCEDURE

TRP to areas of retinal ischemia

Interventions

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0.5 mg ranibizumab

Intervention Type DRUG

Targeted Retinal Photocoagulation (TRP)

TRP to areas of retinal ischemia

Intervention Type PROCEDURE

Other Intervention Names

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Lucentis

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

Greater Houston Retina Research

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Amy C Schefler, MD

Role: PRINCIPAL_INVESTIGATOR

Retina Consultants Houston

Locations

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Texas Retina Associates

Dallas, Texas, United States

Site Status

Retina Consultants of Houston/The Medical Center

Houston, Texas, United States

Site Status

Retina Consultants of Houston

Katy, Texas, United States

Site Status

Retina Consultants of Houston

The Woodlands, Texas, United States

Site Status

Countries

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United States

References

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Finger PT, Chin KJ. High-dose (2.0 mg) intravitreal ranibizumab for recalcitrant radiation retinopathy. Eur J Ophthalmol. 2013 Nov-Dec;23(6):850-6. doi: 10.5301/ejo.5000333. Epub 2013 Jun 28.

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Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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ML29236

Identifier Type: -

Identifier Source: org_study_id

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