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

NCT00470977 | Completed Phase 1

• 1 other identifier: Protocol: FVF4140S
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Coats' Disease; Idiopathic Retinal Telangiectasia; Retinal Angiomatous Proliferation; Polypoidal Choroidal Vasculopathy; Pseudoxanthoma Elasticum; Pathological Myopia; Multi-focal Choroiditis; Rubeosis Iridis; Von Hippel Lindau Disease; BEST VITELLIFORM MACULAR DYSTROPHY, MULTIFOCAL (Disorder)

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of intravitreal injections of ranibizumab in the treatment of non-AMD variants and other CNV related conditions

  24 months

Secondary Outcomes (3)

• 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

Study Arms (1)

(Ranibizumab) Lucentis

EXPERIMENTAL

(Ranibizumab)Lucentis 0.5%

Drug: ranibizumab injection (0.5 mg)

Interventions

ranibizumab injection (0.5 mg) DRUG

ranibizumab 10mg mg/ml. , 0.3ml/vial, 0.05 ml./injection intravitreally for 3months then prn for the next 21 months.

Also known as: Lucentis

(Ranibizumab) Lucentis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects will be eligible 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
• 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.
• Visual acuity of 20/40 to 20/320 in the study eye on the ETDRS visual acuity chart.
• Media clarity, pupillary dilation and patient cooperation sufficient to allow OCT testing and retinal photography

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from this study:
• Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy is initiated
• Participation in another simultaneous medical investigation or trial
• Patient with significantly compromised visual acuity in the study eye due to concomitant ocular conditions.
• Patients who have undergone intraocular surgery within the last 2 months.
• Patient participating in any other investigational drug study.
• 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)
• Patient treated with systemic anti-VEGF or pro-VEGF agents within 3 months before enrollment.
• Previous treatment (in either eye) with intravitreal or intravenously administered Avastin (bevacizumab).
• Inability to obtain photographs to document CNV (including difficulty with venous access).
• Patient with a known adverse reaction to fluorescein dye.
• Patient has a history of any medical condition which would preclude scheduled visits or completion of the study.
• Patient has had insertion of scleral buckle in the study eye
• Patient has received radiation treatment.
• 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.

Sponsors & Collaborators

• Manhattan Eye, Ear & Throat Hospital: lead
• Genentech, Inc.: collaborator

Study Sites (2)

Lenox Hill Hospital/Manhattan Eye Ear and Throat Institute

New York, New York, 10065, United States

Location

Lenox Hill Hospital/Manhattan Eye, Ear & Throat Institute

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Retinal Telangiectasis; Polypoidal Choroidal Vasculopathy; Pseudoxanthoma Elasticum; Myopia, Degenerative; von Hippel-Lindau Disease; Vitelliform Macular Dystrophy

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Telangiectasis; Vascular Diseases; Cardiovascular Diseases; Choroidal Neovascularization; Choroid Diseases; Uveal Diseases; Neovascularization, Pathologic; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hemostatic Disorders; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Myopia; Refractive Errors; Neurocutaneous Syndromes; Nervous System Diseases; Angiomatosis; Ciliopathies; Abnormalities, Multiple; Macular Degeneration; Retinal Degeneration; Eye Diseases, Hereditary

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lawrence A. Yannuzzi, MD

  LuEsther T. Mertz Retinal Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lawrence A. Yannuzzi, M.D.

Study Record Dates

• First Submitted: May 4, 2007
• First Posted: May 8, 2007
• Study Start: May 1, 2007
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: October 25, 2012

Record last verified: 2012-10

Locations

US (2)