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

Polypoidal Choroidal Vasculopathy Clinical Trial

— FVF4140S  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00470977
• Other study ID #: Protocol: FVF4140S
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: May 4, 2007
• Last updated: October 24, 2012
• Start date: May 2007
• Est. completion date: December 2010

Study information

• Verified date: October 2012
• Source: Manhattan Eye, Ear & Throat Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• BEST VITELLIFORM MACULAR DYSTROPHY, MULTIFOCAL (Disorder)
• Choroiditis
• Coats' Disease
• Idiopathic Retinal Telangiectasia
• Macular Degeneration
• Multi-focal Choroiditis
• Myopia, Degenerative
• Pathological Myopia
• Polypoidal Choroidal Vasculopathy
• Pseudoxanthoma Elasticum
• Retinal Angiomatous Proliferation
• Rubeosis Iridis
• Telangiectasis
• Vascular Diseases
• Vitelliform Macular Dystrophy
• Von Hippel Lindau Disease
• Von Hippel-Lindau Disease

Intervention

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.

Locations

Country	Name	City	State
United States	Lenox Hill Hospital/Manhattan Eye Ear and Throat Institute	New York	New York
United States	Lenox Hill Hospital/Manhattan Eye, Ear & Throat Institute	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Manhattan Eye, Ear & Throat Hospital	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of intravitreal injections of ranibizumab in the treatment of non-AMD variants and other CNV related conditions		24 months	Yes
Secondary	Mean change in central retinal thickness as measured by OCT at month 12 compared to baseline		24 months	Yes
Secondary	Change in leakage area seen during fluorescein angiography at month 12 as compared with baseline		24 months	Yes
Secondary	Number of additional injections required following the initial 3 injections		24 months	Yes