Ranibizumab (Lucentis) for Macular Edema Secondary to Vein Occlusions (LVO)

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Peter A Campochiaro, MD, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00407355
First received: December 1, 2006
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

Central and branch retinal vein occlusions are major causes of visual loss. Hemorrhage and capillary nonperfusion, when they involve the macula, can contribute to visual loss, but the major cause is macular edema. Focal and grid laser photocoagulation can sometimes provide benefit in patients with macular edema due to branch vein occlusions, but several laser treatments are often needed and recovery of vision can be very slow and incomplete 1. Laser photocoagulation does not provide benefit for macular edema due to central vein occlusions 2. Therefore, new treatments are needed.The objective of this study is to assess the bioactivity of 3 intravitreous injections 0.5 mg or 0.3 mg of ranibizumab in patients with macular edema due to central and branch retinal vein occlusions and correlate activity with peak and trough aqueous levels. The purpose of this research protocol is pilot study to determine if a randomized placebo controlled trial is warranted.


Condition Intervention Phase
Macular Edema
Retinal Vein Occlusion
Drug: Intravitreal injection of ranibizumab .3 dose
Drug: Intravitreal injection of Ranibizumab .5 dose
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot, Open-Label Study of the Safety, Tolerability, and Bioactivity of Multiple Intravitreal Injections of Ranibizumab in Subjects With Macular Edema Secondary to Vein Occlusions.

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Best Corrected Visual Acuity Change From Baseline at All Visits [ Time Frame: continuous through 72 mos ] [ Designated as safety issue: Yes ]
  • Retinal Thickness Change From Baseline at All Visits [ Time Frame: continuous through 72 mos ] [ Designated as safety issue: Yes ]

Enrollment: 40
Study Start Date: January 2006
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: RBZ 0.3
RBZ at the 0.3 mg dose intravitreal injection
Drug: Intravitreal injection of ranibizumab .3 dose
PRN every 30 days withing retreatment criteria
Active Comparator: RBZ 0.5
RBZ dose level .5 for ITV injection
Drug: Intravitreal injection of Ranibizumab .5 dose
Intravitreal injection of Ranibizumab .5 dose every 30 days PRN with retreatment criteria

Detailed Description:

This study is a phase II, open-label study to investigate the bioactivity and pharmacodynamics of intravitreous ranibizumab in subjects with macular edema due to central and branch retinal vein occlusion. This pilot study will enroll 40 patients, 20 with central vein occlusion and 20 with branch vein occlusion. Each patient will receive three (3) injections of 0.5 or 0.3 mg of ranibizumab. The study consists of a 2-week screening period (Days -14 to -1), a 3-month treatment period, and a 9-month follow-up period. Consented subjects will enter the 14-day screening period to determine eligibility, including serum chemistry and hematology testing, urinalysis, pregnancy testing, and macular thickness based on optical coherence tomography measurements and fluorescein angiography. Patients who have reduction of visual acuity to 20/40 or worse due to foveal thickening from macular edema secondary to central or branch retinal vein occlusion and who meet eligibility criteria will be invited to enroll in the study. Baseline foveal thickness by OCT must be at least 250 um, which is often associated with VA of 20/40 or worse and provides sufficient thickening so that a treatment effect is easily detectable (Nguyen et al. 2004). Every effort will be made to recruit and enroll eligible patients from men and women of all ethnic and social backgrounds. It is expected that the 40 study subjects will be recruited over a 4-month period. Patients who meet entry criteria will be able to enroll in the study until the quota of patients has been achieved. All enrolled patients will receive either 0.5 or 0.3 mg injections of ranibizumab. Forty eligible subjects who have provided informed consent from one site (Wilmer Eye Institute at the Johns Hopkins Medical Institutions) will be enrolled, 20 with central vein occlusion and 20 with branch vein occlusion. In each of the 2 groups, 10 patients will be randomized to 0.5 mg of the ranibizumab, and 10 will be randomized to 0.3 mg of ranibizumab. Subjects will be identified and recruited through the clinic population of the Wilmer Eye Institute, including that of the Vitreoretinal Service and the Retinal Vascular Center, as well as through referral from physicians in the community. Announcement of the study will be made throughout the Wilmer Eye Institute, Johns Hopkins University School of Medicine through newsletters, pamphlets, and the clinical trials web site on the internet and intranet systems. Information about the study will also be sent to the community physicians as well as the ophthalmologists who often refer patients to the Wilmer Eye Institute. Every effort will be made to enroll eligible patients from men and women of all ethnic and social backgrounds.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent and authorization of use and disclosure of protected health information
  • Age greater than or equal to 18 years
  • Diagnosis of macular edema due to central or branch retinal vein occlusion
  • Foveal thickness of over 250 um, as assessed by OCT
  • Best corrected visual acuity score in the study eye of 20/40 to 20/320 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. Visual acuity score in the non-study eye must be greater than 25 letters (approximate Snellen equivalent 20/320).
  • 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
  • In the opinion of the investigator, laser photocoagulation can be withheld for at least 30 days after the patient has enrolled in the study

Exclusion Criteria:

  • Prior/Concomitant Treatment

    • Scatter laser photocoagulation or macular photocoagulation within 3 months of study entry in the study eye
    • Use of intraocular or periocular injection of steroids in the study eye (e.g., triamcinolone) within 3 months of study entry
    • Previous participation in a study and receipt of anti-angiogenic drugs (pegaptanib sodium [EYE001], ranibizumab, anecortave acetate, protein kinase C inhibitor, etc.) within 3 months of study entry Concurrent Ocular Conditions
    • Vitreomacular traction or epiretinal membrane in the study eye evident biomicroscopically or by OCT
    • Ocular inflammation (including 1+ or above in the amount of cells) in the study eye
    • History of idiopathic or autoimmune uveitis in either eye
    • Structural damage to the center of the macula in the study eye 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), macular ischemia, or organized hard exudate plaque
    • Ocular disorders in the study eye that may confound interpretation of study results, including diabetic retinopathy, retinal detachment, macular hole, or choroidal neovascularization of any cause (e.g., AMD, ocular histoplasmosis, or pathologic myopia)
    • Concurrent disease in the study eye that could compromise visual acuity or require medical or surgical intervention during the study period
    • Intraocular surgery in the study eye within 3 months of study entry
    • During the study, if patients need to have cataract surgery, the patients will undergo the necessary cataract or any other surgery and will continued to be treated per protocol and followed.
    • Uncontrolled glaucoma (defined as intraocular pressure greater than 30 mm Hg despite treatment with anti-glaucoma medication) or previous filtration surgery in the study eye
    • Infectious blepharitis, keratitis, scleritis, or conjunctivitis (in either eye) or current treatment for serious systemic infection Systemic Conditions
    • Blood pressure exceeding 160/95 (sitting) during the screening period
    • Renal failure requiring dialysis or renal transplant
    • Premenopausal women not using adequate contraception
    • Previous participation in other studies of investigational drugs (excluding vitamins and minerals) within 3 months
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00407355

Locations
United States, Maryland
Wilmer Eye Institute
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Peter A Campochiaro, MD
Genentech
Investigators
Principal Investigator: Peter A Campochiaro, MD Johns Hopkins University
  More Information

No publications provided by Johns Hopkins University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Peter A Campochiaro, MD, Principal Investigator, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00407355     History of Changes
Other Study ID Numbers: 05-06-09-05
Study First Received: December 1, 2006
Results First Received: October 7, 2013
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Johns Hopkins University:
vein occlusion
macular edema

Additional relevant MeSH terms:
Edema
Macular Edema
Retinal Vein Occlusion
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Venous Thrombosis
Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on April 17, 2014