Widefield Angiography Guided Targeted-retinal Photocoagulation Combined With Anti VEgf Intravitreal Injections for the Treatment of Ischemic Central Retinal Vein Occlusion, Hemi Retinal Vein Occlusion, and Branch Retinal Vein Occlusion (WAVE)

August 8, 2017 updated by: Charles C Wykoff, PhD, MD

A Phase IV Open Label Trial of the Safety, Tolerability and Efficacy of 0.5mg Ranibizumab Intravitreal Injections Combined With Wide Field Angiography Guided Panretinal Photocoagulation vs. 0.5mg Ranibizumab Intravitreal Injection Monotherapy in Subjects With Ischemic Central Retinal Vein Occlusion, Hemi Retinal Vein Occlusion, and Branch Retinal Vein Occlusion Who Incompletely Respond to at Least 2 Consecutive Intravitreal Injections in the Past 4 Months.

To see if Lucentis 0.5mg combined with Targeted Pan Retinal photocoagulation will decrease the total number of intravitreal injections in a year for ischemic central retinal vein occlusion, hemi-retinal vein occlusions and branch retinal vein occlusions compared to standard of care

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The WAVE trial is a phase IV, open label, 12-month trial of intravitreal ranibizumab 0.5 mg in patients (n=30) with ischemic CRVO, HRVO and BRVO who have been previously treated with ranibizumab or any other anti-VEGF intravitreal injection therapy, who are incomplete responders to 2 or more consecutive intravitreal anti-VEGF injections in the past 4 months. Randomization is 1:4, 1=control, ranibizumab only, 4=treatment arm. In total, 6 subjects will be randomized to control and 24 randomized to treatment arm.

Cohort 1- 24 Subjects previously treated Patients will receive 6 doses of ranibizumab 0.5 mg, followed by PRN intravitreal injection of ranibizumab 0.5 mg based on pre-defined retreatment criteria for up to 11 total injections.

Wide field angiography guided peripheral targeted-retinal photocoagulation (TRP), will be divided into 2 sessions if needed, one at the 2 weeks post injection visit and another later at M4/V7, if repeat wide field angiogram indicates areas not sufficiently treated in the first TRP session

Cohort 2- 6 Subjects, previously treated patients will receive 6 doses of ranibizumab 0.5 mg, followed by PRN intravitreal injection of ranibizumab 0.5 mg based on pre-defined retreatment criteria for up to 11 total injections.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • Retina Consultants of Houston/The Medical Center
      • Katy, Texas, United States, 77494
        • Retina Consultants of Houston
      • The Woodlands, Texas, United States, 77384
        • Retina Consultants of Houston

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age > 18 years
  • Visual acuity between 20/25 and 20/800, ETDRS best corrected visual acuity
  • Ability to provide written informed consent and comply with study assessments for the full duration of the study

Patients previously treated with any ITV anti-VEGF:

• With at least 2 consecutive monthly intravitreal injections of anti-VEGF medications with presence of persistent or recurrent macular edema in the past 4 months

Exclusion Criteria:

  • IOP over 30 mm Hg
  • Any previous retinal laser photocoagulation to the study eye
  • Previous intravitreal injection in the study eye of any corticosteroid treatment
  • Previous vitrectomy in study eye (posterior or anterior associated with vitreous loss in cataract surgery)
  • Intracapsular cataract extraction
  • Any previous radiation treatments to head/neck that the principal or sub investigator feels is clinically relevant
  • Inability to assess iris or angle neovascularization (corneal opacity precluding gonioscopy)
  • Significant cardiovascular disease or cancer that would prevent follow-up visits or completion of the 12 month study
  • Significant diabetic retinopathy in the fellow eye (diabetic macular edema, proliferative diabetic retinopathy, or high-risk non-proliferative diabetic retinopathy)
  • Participation in another simultaneous medical investigator or trial
  • Ocular disorders or concurrent disease in the study eye that may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention, including history of retinal detachment, macular hole, or choroidal neovascularization of any cause (e.g., DME, AMD, ocular histoplasmosis, or pathologic myopia)
  • Structural damage to the center of the macula in the study eye prior to CRVO, HRVO and BRVO likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s)
  • Vitreomacular traction or clinically significant epiretinal membrane in the study eye evident biomicroscopically or by OCT (vitreomacular attachment OK)
  • Infectious blepharitis, keratitis, scleritis, or conjunctivitis (in either eye) or current treatment for serious systemic infection
  • Spherical equivalent of the refractive error in the study eye of more than -8 diopters myopia (For patients who have had refractive or cataract surgery in the study eye, preoperative spherical equivalent refractive error of more than -8 diopters myopia is not allowed)
  • Uncontrolled Blood pressure: defined as systolic pressure > 180mmHg and/or diastolic pressure of >110 mm Hg (sitting) during the screening period
  • Uncontrolled diabetes mellitus
  • Renal failure requiring dialysis or renal transplant
  • 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.
  • History of other disease, metabolic dysfunction, physical examination finding, or other findings giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug, might affect interpretation of the results of the study, or render the subject at high risk from treatment complications
  • History of allergy to fluorescein, not amenable to treatment
  • Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed by the principal investigator (PI) and/or the sub-investigator.
  • History of allergy to humanized antibodies or any component of the ranibizumab formulation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Targeted Pan Retinal laser combined with 0.5mg ranibizumab
Cohort 1 (n=24), previously treated with at least 2 consecutive or more intravitreal injections of any anti-VEGF agent with persistent or recurrent macular edema will receive 6 loading doses of 0.5 mg ranibizumab followed by PRN treatment with ranibizumab 0.5 mg; after receiving the first loading dose of ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) based on 200° wide field angiography with possibility of a second session of TRP at M4/M7, if non-perfusion persists based on angiogram.The 200°wide field angiography will indicate areas of peripheral ischemia which will be selectively treated, preserving areas of more perfused retina.
Drug: 0.5mg Ranibizumab
intravitreal injections
Other Names:
  • Lucentis
Procedure: Targeted Pan Retinal Photocoagulation
Targeted Pan Retinal Photocoagulation based on wide field angiography
Other Names:
  • PRP
  • Pan Retinal Photocoagulation
  • TRP
  • Pan Laser
Active Comparator: Ranibizumab 0.5mg
Cohort 2 (n=6), previously treated with at least 2 consecutive or more intravitreal injections of any anti-VEGF agent with persistent or recurrent macular edema will receive 6 loading doses followed by PRN monthly treatment with ranibizumab 0.5 mg.
Drug: 0.5mg Ranibizumab
intravitreal injections
Other Names:
  • Lucentis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Number of Intravitreal Injections Over a 12 Month Period
Time Frame: 12 months
Assess the number of intravitreal injections over 12 months.
12 months
Visual Acuity
Time Frame: 12 month period
Evaluate the mean change from baseline in ETDRS best-corrected visual acuity at 12 months. The ETDRS protocol is a widely accepted international standard for macular laser photocoagulation treatment. A higher score represents better functioning.
12 month period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Retinal Ischemia
Time Frame: 12 month period
Quantify change in area of perfused and ischemic retina.
12 month period
Foveal Avascular Zone
Time Frame: 12 months
Assess change in foveal avascular zone area and largest diameter, measured during the early phase of the angiogram
12 months
Adverse Events
Time Frame: 12 months
Incidence and severity of adverse events (ocular and non-ocular).
12 months
Neovascularization of the Iris, Optic Nerve and Elsewhere
Time Frame: 12 months
Percent of patients that develop neovascularization of the iris, optic nerve and/or elsewhere.
12 months
Central Foveal Outcome
Time Frame: 12 months
Mean change in Central Foveal Volume on High Resolution OCT.
12 months
Aqueous VEGF Levels
Time Frame: 12 Months
VEGF, other cytokines and ranibizumab levels in aqueous and serum samples at randomization and at the exit or early termination visit.
12 Months
Visual Field
Time Frame: 6 and 12 Months
Goldman Visual Field changes at 6 and 12 months from baseline. Goldmann perimetry is a method used to map a patient's field of vision (central and peripheral). Changes will be assessed by manual digital quantification of GVF plots.
6 and 12 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Charles C Wykoff, PhD, MD

Collaborators

Genentech, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2012

Primary Completion (Actual)

October 1, 2015

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

October 17, 2012

First Submitted That Met QC Criteria

October 17, 2012

First Posted (Estimate)

October 19, 2012

Study Record Updates

Last Update Posted (Actual)

September 8, 2017

Last Update Submitted That Met QC Criteria

August 8, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12246

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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