Treatment of Exudative and Vasogenic Chorioretinal Diseases Including Variants of AMD and Other CNV Related Maculopathy (FVF4140S)

Treatment of Exudative and Vasogenic Chorioretinal Diseases Including Variants of AMD and Other CNV Related Maculopathy With Intravitreal Injection of Lucentis (Ranibizumab Injection)

The purpose of this study is to evaluate the safety and tolerability of intravitreal injections of ranibizumab in the treatment of AMD variants and other choroidal neovascularization (CNV) related conditions (Coats' disease, idiopathic perifoveal telangiectasia, retinal angiomatous proliferation, polypoidal vasculopathy, pseudoxanthoma elasticum, pathological myopia, multi-focal choroiditis, rubeosis iridis) using the incidence and severity of adverse events.

Limited forms of treatment are available that limit the loss of visual acuity. However, the patients may not have any substantial improvement in acuity or function. Therefore there remains a significant unmet need for therapeutic options managing the neovascularization and its consequences.

Lucentis (ranibizumab) injection will be considered as an attempt to control the growth of the abnormal vessels because of evidence suggesting that angiogenic factors, such as vascular endothelial growth factor (VEGF), play a role in the pathogenesis of neovascular non-AMD conditions.

The rationale for the study design is as follows:

A 0.5 mg dose of Lucentis (ranibizumab), a commercially available preparation that is Food and Drug Administration (FDA) approved and labeled for intravitreal injection use for neovascular (wet) age-related macular degeneration will be used.

In AMD variants and other CNV related conditions, vascular endothelial growth factor (VEGF) plays a role in the pathogenesis as in neovascular AMD.

Intravitreal injection of ranibizumab delivers maximal concentration of the antibody fragment to the vitreous cavity with minimal systemic exposure. The dosing schedule, based on considerations of the half-life and the clinical response in patients with neovascularization suggests that a 1-month interval is optimal.

Study Overview

• Status: Completed
• Conditions: Polypoidal Choroidal Vasculopathy; Pseudoxanthoma Elasticum; Pathological Myopia; Retinal Angiomatous Proliferation; Coats' Disease; Idiopathic Retinal Telangiectasia; Multi-focal Choroiditis; Rubeosis Iridis; Von Hippel Lindau Disease; BEST VITELLIFORM MACULAR DYSTROPHY, MULTIFOCAL (Disorder)
• Intervention / Treatment: Drug: ranibizumab injection (0.5 mg)

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Lenox Hill Hospital/Manhattan Eye Ear and Throat Institute
    • New York, New York, United States, 10065
      • Lenox Hill Hospital/Manhattan Eye, Ear & Throat Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects will be eligible if the following criteria are met:

1. Ability to provide written informed consent and comply with study assessments for the full duration of the study
2. Age > 18 years
3. Clinical diagnosis of the following conditions: Coats' disease, idiopathic perifoveal telangiectasia, retinal angiomatous proliferation, polypoidal vasculopathy, pseudoxanthoma elasticum, pathological myopia, multi-focal choroiditis, rubeosis iridis.
4. Visual acuity of 20/40 to 20/320 in the study eye on the ETDRS visual acuity chart.
5. Media clarity, pupillary dilation and patient cooperation sufficient to allow OCT testing and retinal photography

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from this study:

1. Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy is initiated
2. Participation in another simultaneous medical investigation or trial
3. Patient with significantly compromised visual acuity in the study eye due to concomitant ocular conditions.
4. Patients who have undergone intraocular surgery within the last 2 months.
5. Patient participating in any other investigational drug study.
6. Use of an investigational drug or treatment related or unrelated to the patient's condition within 30 days prior to receipt of study medication (verteporfin, pegaptanib, or other AMD therapy in the study eye)
7. Patient treated with systemic anti-VEGF or pro-VEGF agents within 3 months before enrollment.
8. Previous treatment (in either eye) with intravitreal or intravenously administered Avastin (bevacizumab).
9. Inability to obtain photographs to document CNV (including difficulty with venous access).
10. Patient with a known adverse reaction to fluorescein dye.
11. Patient has a history of any medical condition which would preclude scheduled visits or completion of the study.
12. Patient has had insertion of scleral buckle in the study eye
13. Patient has received radiation treatment.
14. Aphakia or absence of the posterior capsule in the study eye. Previous violation of the posterior capsule in the study eye is also excluded unless as a result of yttrium aluminum garnet (YAG) posterior capsulotomy in association with posterior chamber lens implantation.
15. Pregnancy (positive pregnancy test) or lactation.
16. 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 intrauterine device (IUD), or contraceptive hormone implant or patch.
17. History of glaucoma filtering surgery in the study eye.
18. Concurrent use of more than two therapies for glaucoma.
19. Uncontrolled glaucoma in the study eye (defined as intraocular pressure > 30 mm Hg despite treatment with anti-glaucoma medication)
20. Inability to comply with study or follow-up procedure

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: (Ranibizumab) Lucentis; (Ranibizumab)Lucentis 0.5%	Drug: ranibizumab injection (0.5 mg); ranibizumab 10mg mg/ml. , 0.3ml/vial, 0.05 ml./injection intravitreally for 3months then prn for the next 21 months.; Other Names: Lucentis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of intravitreal injections of ranibizumab in the treatment of non-AMD variants and other CNV related conditions	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean change in central retinal thickness as measured by OCT at month 12 compared to baseline	24 months
Change in leakage area seen during fluorescein angiography at month 12 as compared with baseline	24 months
Number of additional injections required following the initial 3 injections	24 months

Collaborators and Investigators

• Sponsor: Manhattan Eye, Ear & Throat Hospital
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Lawrence A. Yannuzzi, MD, LuEsther T. Mertz Retinal Research Center

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: May 4, 2007
• First Submitted That Met QC Criteria: May 7, 2007
• First Posted (Estimate): May 8, 2007

Study Record Updates

• Last Update Posted (Estimate): October 25, 2012
• Last Update Submitted That Met QC Criteria: October 24, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Skin Diseases; Eye Diseases; Congenital Abnormalities; Hematologic Diseases; Retinal Degeneration; Retinal Diseases; Hemorrhagic Disorders; Genetic Diseases, Inborn; Connective Tissue Diseases; Hemostatic Disorders; Panuveitis; Uveitis; Uveal Diseases; Skin Diseases, Genetic; Eye Diseases, Hereditary; Choroid Diseases; Refractive Errors; Skin Abnormalities; Abnormalities, Multiple; Neurocutaneous Syndromes; Ciliopathies; Angiomatosis; Myopia; Uveitis, Posterior; White Dot Syndromes; Macular Degeneration; Telangiectasis; Von Hippel-Lindau Disease; Pseudoxanthoma Elasticum; Myopia, Degenerative; Retinal Telangiectasis; Choroiditis; Multifocal Choroiditis; Vitelliform Macular Dystrophy; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: Protocol: FVF4140S