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

NCT00390208 | Completed Phase 2 DMC

• 1 other identifier: PDEX
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Age Related Macular Degeneration

Keywords

Macular Degeneration; Degenerative changes in the macula lutea of the retina.; Maculopathy, Age-Related; Age-Related Maculopathies; Age-Related Maculopathy; Maculopathies, Age-Related; RETINAL DEGENERATION; ARMD; AMD; Lucentis; Visudyne; Photodynamic Therapy; Verteporfin; Ranibizumab; Intravitreal Dexamethasone

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Lesion size

  one year

• Lesion leakage

  one year

• OCT measurement of macular thickness, subretinal fluid and cystoid edema

  one year

• Total number of treatments required

  one year

• Timing of visual improvement after initiation of therapy

  one year

Study Arms (2)

Group 1

OTHER

Combination triple therapy of Lucentis, Dexamethasone and Visudyne Therapy

Drug: ranibizumab, dexamethasone and verteporfin

Group 2

OTHER

Monotherapy: One 0.5 mg intravitreal Ranibizumab injection

Drug: Ranibizumab

Interventions

ranibizumab, dexamethasone and verteporfin DRUG

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.

Group 1

Ranibizumab DRUG

One 0.5 mg intravitreal Ranibizumab injection

Group 2

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bay Area Retina Associates: lead
• QLT Inc.: collaborator

Study Sites (4)

Bay Area Retina Associates

Castro Valley, California, 94546, United States

Location

Bay Area Retina Associates

Walnut Creek, California, 94598, United States

Location

Georgia Retina

Riverdale, Georgia, 30274, United States

Location

Retina Vitreous Associates

Toledo, Ohio, 43608, United States

Location

Related Publications (16)

• 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. doi: 10.1001/archopht.120.11.1443.

  PMID: 12427056 BACKGROUND

• 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. doi: 10.1016/j.ophtha.2006.02.027. Epub 2006 Apr 27.

  PMID: 16647134 BACKGROUND

• 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. doi: 10.1016/j.ophtha.2005.11.019. Epub 2006 Feb 3.

  PMID: 16458968 BACKGROUND

• 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. doi: 10.1016/j.exer.2004.09.013.

  PMID: 15670803 BACKGROUND

• 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. doi: 10.1016/j.ophtha.2004.08.012.

  PMID: 15691567 BACKGROUND

• 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. doi: 10.1016/s0161-6420(99)00139-6.

  PMID: 10711885 BACKGROUND

• 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. doi: 10.1167/iovs.04-0905.

  PMID: 15790913 BACKGROUND

• 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.

  PMID: 12757090 BACKGROUND

• 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. doi: 10.1007/BF00172263.

  PMID: 2004725 BACKGROUND

• Schmidt-Erfurth U, Schlotzer-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. doi: 10.1167/iovs.02-1115.

  PMID: 14507895 BACKGROUND

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

  PMID: 11381074 BACKGROUND

• 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. doi: 10.1016/j.ajo.2005.11.058.

  PMID: 16564797 BACKGROUND

• Nicolo 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. doi: 10.1097/00006982-200601000-00010.

  PMID: 16395140 BACKGROUND

• 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. doi: 10.1097/01.iae.0000238561.99283.0e.

  PMID: 16603955 BACKGROUND

• Maturi RK, Bleau LA, Wilson DL. Electrophysiologic findings after intravitreal bevacizumab (Avastin) treatment. Retina. 2006 Mar;26(3):270-4. doi: 10.1097/00006982-200603000-00003.

  PMID: 16508425 BACKGROUND

• Manzano RP, Peyman GA, Khan P, Kivilcim M. Testing intravitreal toxicity of bevacizumab (Avastin). Retina. 2006 Mar;26(3):257-61. doi: 10.1097/00006982-200603000-00001.

  PMID: 16508423 BACKGROUND

Related Links

• Study Sponsor website

MeSH Terms

Conditions

Macular Degeneration; Retinal Degeneration

Interventions

Ranibizumab; Dexamethasone; Verteporfin

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; 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; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Porphyrins; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds

Study Officials

• Subhransu K Ray, M.D., Ph.D.

  Bay Area Retina Associates

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 17, 2006
• First Posted: October 19, 2006
• Study Start: August 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2009
• Last Updated: May 27, 2010

Record last verified: 2010-05

Locations

US (4)