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

Overview

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.

Full Title of Study: “A Prospective Masked Pilot Study Comparing Group 1 Triple Therapy – PDT Plus IVD and Intravitreal Ranibizumab Versus Group 2 Monotherapy – Intravitreal Ranibizumab Alone.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Single (Outcomes Assessor)
  • Study Primary Completion Date: December 2008

Detailed 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.

Interventions

  • 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.
  • Drug: Ranibizumab
    • One 0.5 mg intravitreal Ranibizumab injection

Arms, Groups and Cohorts

  • Other: Group 1
    • Combination triple therapy of Lucentis, Dexamethasone and Visudyne Therapy
  • Other: Group 2
    • Monotherapy: One 0.5 mg intravitreal Ranibizumab injection

Clinical Trial Outcome Measures

Primary Measures

  • 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.
    • Time Frame: one year

Secondary Measures

  • Lesion size
    • Time Frame: one year
  • Lesion leakage
    • Time Frame: one year
  • OCT measurement of macular thickness, subretinal fluid and cystoid edema
    • Time Frame: one year
  • Total number of treatments required
    • Time Frame: one year
  • Timing of visual improvement after initiation of therapy
    • Time Frame: one year

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 50 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Bay Area Retina Associates
  • Collaborator
    • QLT Inc.
  • Provider of Information About this Clinical Study
    • Subhransu K. Ray, M.D., Ph.D., Bay Area Retina Associates
  • Overall Official(s)
    • Subhransu K Ray, M.D., Ph.D., Principal Investigator, Bay Area Retina Associates

References

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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.

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.

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.

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.

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.

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.

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.

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