Triple Therapy - PDT Plus IVD and Intravitreal Ranibizumab Versus Lucentis Monotherapy to Treat Age-Related Macular Degeneration

Age Related Macular Degeneration Clinical Trial

— PDEX  

Official title:

A Prospective Masked Pilot Study Comparing Group 1 Triple Therapy - PDT Plus IVD and Intravitreal Ranibizumab Versus Group 2 Monotherapy - Intravitreal Ranibizumab Alone.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00390208
• Other study ID #: PDEX
• Status: Completed
• Phase: Phase 2
• First received: October 17, 2006
• Last updated: May 25, 2010
• Start date: August 2006
• Est. completion date: December 2009

Study information

• Verified date: May 2010
• Source: Bay Area Retina Associates
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare triple therapy using Photodynamic therapy, intravitreal Dexamethasone and intravitreal Ranibizumab injections versus monotherapy with intravitreal Ranibizumab alone for the treatment of Age-Related Macular Degeneration.

Description:

This is a twelve month Phase II prospective masked study comparing Group 1 triple therapy:

Same day combination therapy with PDT, 500 microgram dose (0.05cc) intravitreal dexamethasone injection (10mg/ml vial), and a single 0.5 mg intravitreal Ranibizumab injection. This will be compared to Group 2 monotherapy: one intravitreal injection of 0.5 mg Lucentis given every four weeks on a set dosing schedule. Sixty consecutive patients will be enrolled into this clinical trial utilizing the current standard of care guidelines as used at Bay Area Retina Associates. Angiography, fundus photography will be performed at the initial visit and quarterly follow-up visits. Only OCT testing will be performed at all other follow-up visits. Both groups will be re-evaluated for safety at 12 and 24 months.

Group 1 Following the initial treatment, all future re-treatments with Lucentis will be determined on a PRN basis. The decision will be based on clinical examination and imaging evidence of lesion activity. Any evidence of subretinal fluid or cystoid edema on OCT or clinical examination, or evidence of leakage on angiogram will result in re-treatment. If after three consecutive Ranibizumab injections in Group 1, there is any evidence of lesion recurrence or growth of the neovascular membrane associated with visual decline or persistent subretinal fluid, the patient will be treated with repeat PDT/IVD/Lucentis The decision to retreat Group 1 with ranibizumab at each monthly follow-up visit will be dependent on clinical exam, OCT measurements or angiographic findings as documented below.

Group 2 Subjects will receive one intravitreal injection of 0.5 mg Lucentis every four weeks until week 48 or as indicated on the FDA approval label.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 2009
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Best Corrected Visual Acuity using ETDRS Charts between 20/32 and 20/400 (Snellen Equivalent) in the study eye with evidence of neovascular ARMD.

(Only one eye will be eligible for study. If both eyes are eligible, the one with the better visual acuity will be selected for treatment unless, based on medical reasons, the investigator deems the other eye to be more appropriate for treatment and study.)

• All lesion subtypes will be enrolled with the following criteria

• Predominantly classic:

• Classic lesion greater than 50% of the total lesion area

• Lesion must be less than 12 disc areas

• Minimally classic or occult:

• CNVM must be greater than or equal to 50% of the total lesion size.

• There must be some evidence of recent disease progression (heme, vision loss, recent lesion growth on FA)

• Lesion size must be less than 12 disc areas.

• Occult:

• Lesions must show recent activity progression with respect to vision, subretinal hemorrhage or subretinal fluid

• Less than 12 disc areas in total size

• Signed informed consent

• Age greater than or equal to 50 years

Exclusion Criteria:

• Pigment epithelial detachment greater than 50% of the total lesion size

• Previous treatment for ARMD in the study eye

• Previous intravitreal drug delivery in the study eye

• History of vitrectomy in the study eye

• Fibrosis or atrophy involving the center of the fovea in the study eye

• Neovascular membrane from any other concurrent retinal disease such as high myopia (SER > -8D), histoplasmosis or other ocular inflammatory disease.

• Known history of glaucoma and on more than one topical medication

• History of glaucoma filtering surgery in the study eye

• History of corneal transplant in the study eye

• Patients with co-existing macular disease such as diabetic macular edema

• Active intraocular inflammation in the study eye

• History of allergy to fluorescein not amenable to treatment

• Inability to comply with study or follow up procedures

Related Conditions & MeSH terms

• Age Related Macular Degeneration
• Macular Degeneration

Intervention

Drug:
• ranibizumab, dexamethasone and verteporfin
One 500 microgram dose (0.05cc) intravitreal dexamethasone (10 mg/ml vial) in combination with Visudyne Photodynamic Therapy and 0.5 mg intravitreal Ranibizumab injection on the same day.
• Ranibizumab
One 0.5 mg intravitreal Ranibizumab injection

Locations

Country	Name	City	State
United States	Bay Area Retina Associates	Castro Valley	California
United States	Georgia Retina	Riverdale	Georgia
United States	Retina Vitreous Associates	Toledo	Ohio
United States	Bay Area Retina Associates	Walnut Creek	California

Sponsors (2)

Lead Sponsor	Collaborator
Bay Area Retina Associates	QLT Inc.

Country where clinical trial is conducted

United States, 

References & Publications (16)

Augustin AJ, Schmidt-Erfurth U. Verteporfin and intravitreal triamcinolone acetonide combination therapy for occult choroidal neovascularization in age-related macular degeneration. Am J Ophthalmol. 2006 Apr;141(4):638-45. — View Citation

Avery RL, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology. 2006 Mar;113(3):363-372.e5. Epub 2006 Feb 3. — View Citation

Blankenship GW. Evaluation of a single intravitreal injection of dexamethasone phosphate in vitrectomy surgery for diabetic retinopathy complications. Graefes Arch Clin Exp Ophthalmol. 1991;229(1):62-5. — View Citation

Bressler NM, Arnold J, Benchaboune M, Blumenkranz MS, Fish GE, Gragoudas ES, Lewis H, Schmidt-Erfurth U, Slakter JS, Bressler SB, Manos K, Hao Y, Hayes L, Koester J, Reaves A, Strong HA; Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Verteporfin therapy of subfoveal choroidal neovascularization in patients with age-related macular degeneration: additional information regarding baseline lesion composition's impact on vision outcomes-TAP report No. 3. Arch Ophthalmol. 2002 Nov;120(11):1443-54. — View Citation

Chalam KV, Malkani S, Shah VA. Intravitreal dexamethasone effectively reduces postoperative inflammation after vitreoretinal surgery. Ophthalmic Surg Lasers Imaging. 2003 May-Jun;34(3):188-92. — View Citation

Edelman JL, Lutz D, Castro MR. Corticosteroids inhibit VEGF-induced vascular leakage in a rabbit model of blood-retinal and blood-aqueous barrier breakdown. Exp Eye Res. 2005 Feb;80(2):249-58. — View Citation

Manzano RP, Peyman GA, Khan P, Kivilcim M. Testing intravitreal toxicity of bevacizumab (Avastin). Retina. 2006 Mar;26(3):257-61. — View Citation

Maturi RK, Bleau LA, Wilson DL. Electrophysiologic findings after intravitreal bevacizumab (Avastin) treatment. Retina. 2006 Mar;26(3):270-4. — View Citation

Nicolò M, Ghiglione D, Lai S, Nasciuti F, Cicinelli S, Calabria G. Occult with no classic choroidal neovascularization secondary to age-related macular degeneration treated by intravitreal triamcinolone and photodynamic therapy with verteporfin. Retina. 2006 Jan;26(1):58-64. — View Citation

Schmidt-Erfurth U, Schlötzer-Schrehard U, Cursiefen C, Michels S, Beckendorf A, Naumann GO. Influence of photodynamic therapy on expression of vascular endothelial growth factor (VEGF), VEGF receptor 3, and pigment epithelium-derived factor. Invest Ophthalmol Vis Sci. 2003 Oct;44(10):4473-80. — View Citation

Shah GK, Stein JD, Sharma S, Sivalingam A, Benson WE, Regillo CD, Brown GC, Tasman W. Visual outcomes following the use of intravitreal steroids in the treatment of postoperative endophthalmitis. Ophthalmology. 2000 Mar;107(3):486-9. — View Citation

Spaide RF, Laud K, Fine HF, Klancnik JM Jr, Meyerle CB, Yannuzzi LA, Sorenson J, Slakter J, Fisher YL, Cooney MJ. Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration. Retina. 2006 Apr;26(4):383-90. — View Citation

Spaide RF, Sorenson J, Maranan L. Photodynamic therapy with verteporfin combined with intravitreal injection of triamcinolone acetonide for choroidal neovascularization. Ophthalmology. 2005 Feb;112(2):301-4. — View Citation

Tamura H, Miyamoto K, Kiryu J, Miyahara S, Katsuta H, Hirose F, Musashi K, Yoshimura N. Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina. Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1440-4. — View Citation

VEGF Inhibition Study in Ocular Neovascularization (V.I.S.I.O.N.) Clinical Trial Group, D'Amico DJ, Masonson HN, Patel M, Adamis AP, Cunningham ET Jr, Guyer DR, Katz B. Pegaptanib sodium for neovascular age-related macular degeneration: two-year safety results of the two prospective, multicenter, controlled clinical trials. Ophthalmology. 2006 Jun;113(6):992-1001.e6. Epub 2006 Apr 27. — View Citation

Wenzel A, Grimm C, Seeliger MW, Jaissle G, Hafezi F, Kretschmer R, Zrenner E, Remé CE. Prevention of photoreceptor apoptosis by activation of the glucocorticoid receptor. Invest Ophthalmol Vis Sci. 2001 Jun;42(7):1653-9. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Visual Acuity: Change in visual acuity by 15 or more ETDRS letters at 6 and 12 months. Non-inferiority as compared to the triple therapy arm will serve to determine efficacy for the purposes of this pilot trial.		one year
Secondary	Lesion size		one year
Secondary	Lesion leakage		one year
Secondary	OCT measurement of macular thickness, subretinal fluid and cystoid edema		one year
Secondary	Total number of treatments required		one year
Secondary	Timing of visual improvement after initiation of therapy		one year

External Links

•   Study Sponsor website