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Adjunctive Photodynamic Therapy + Aflibercept vs. Afilbercept Alone for PDA in NV AMD

This study has been withdrawn prior to enrollment.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02457026
First Posted: May 29, 2015
Last Update Posted: July 26, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Bausch & Lomb Incorporated
Information provided by (Responsible Party):
Duke University
  Purpose
The purpose of this prospective interventional study is to assess whether adjunctive verteporfin photodynamic therapy (PDT) is effective for the treatment of persistent disease activity in neovascular age-related macular degeneration (NV AMD), as compared to anti-VEGF therapy (aflibercept) alone. This study will enroll individuals with NV AMD who have persistent disease activity in spite of either loading dose (initial 3-5 anti-VEGF treatments) or maintenance (established course) anti-VEGF therapy to determine whether PDT can improve disease activity, facilitate sustained visual acuity gains, and decrease burden of frequent anti-VEGF treatments for affected patients. Risks of study are related to treatment with study drugs: intravenous verteporfin, intravitreal triamcinolone acetonide, and intravitreal aflibercept. All have been studied extensively in clinical trials and are established treatments used routinely in NV AMD. Adverse events will be monitored by the principal investigator and study team.

Condition Intervention
Neovascular Age-related Macular Degeneration Drug: Aflibercept Drug: Triamcinolone Acetonide Drug: Verteporfin

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adjunctive Photodynamic Therapy + Aflibercept vs. Afilbercept Alone for PDA in Patients With Neovascular Age-Related Macular Degeneration

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Percentage of individuals with resolution or major reduction in PDA [ Time Frame: up to 8 weeks after loading dose ]
  • Percentage of individuals with sustained visual acuity [ Time Frame: 1 year after loading dose ]
  • Average number of aflibercept injections [ Time Frame: 1 year after loading dose ]

Secondary Outcome Measures:
  • Frequency of case with progressive disease on therapy [ Time Frame: 6 months post-PDT treatment ]
  • Mean change in choroidal neovascularization lesion size by fluorescein angiography from baseline [ Time Frame: 6 months post-PDT treatment ]
  • Mean change in central foveal thickness by SD-OCT [ Time Frame: 6 months post-PDT treatment ]
  • Mean change in best-corrected ETDRS visual acuity from baseline [ Time Frame: 6 months post-PDT treatment ]
  • Percentage of participants with 2-line ETDRS visual acuity gain [ Time Frame: 6 months post-PDT treatment ]
  • Percentage of participants with 2-line ETDRS visual acuity loss [ Time Frame: 6 months post-PDT treatment ]

Enrollment: 0
Study Start Date: January 2016
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adjunctive PDT + Aflibercept
Participants will receive adjunctive verteporfin PDT at Study Visit 1 as well as intravitreal aflibercept at Study Visits 1, 2, 3. At Study Visit 4, participants will have repeat assessment of disease activity. If disease activity is resolved or trivial, the individual will be maintained on aflibercept injections. If PDA remains unresolved, the individual will undergo repeat verteporfin PDT at Study Visit 4, as well as intravitreal aflibercept at Study Visits 4, 5, and 6. Disease activity will be reassessed at Study Visit 7. If disease activity is resolved or trivial, the individual will be switched to aflibercept injections once every three months. If PDA remains unresolved, then the individual will default to a standard-of-care treatment strategy with aflibercept (monthly injections).
Drug: Aflibercept
Aflibercept is a recombinant fusion protein consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1.
Other Name: Eylea
Drug: Triamcinolone Acetonide
Triamcinolone Acetonide is a synthetic corticosteroid indicated for treatment of ocular inflammatory conditions, uveitis, sympathetic ophthalmia, and temporal arteritis.
Other Name: Triesence
Drug: Verteporfin
Verteporfin is a benzoporphyrin derivative, and is a medication used as a photosensitizer for photodynamic therapy.
Other Name: Visudyne
Active Comparator: Aflibercept Alone
Participants in this group will receive intravitreal aflibercept at Study Visits 1, 2, and 3. At Study Visit 4, participants will have repeat assessment of disease activity. From Study Visit 4 onwards, aflibercept will be administered according to a "treat-and-extend" strategy. If disease activity is considered to be resolved or trivial, then the interval between treatments can be initially "extended" from every 28 days to every 42 days. If disease activity remains stable, treatments can be extended in 14-day increments, up to 10 weeks between treatments. For individuals who have PDA that remains unresolved, aflibercept will continue to be administered every days, but if disease quiescence is achieve at a later time point, the treatment period can be extended at that time.
Drug: Aflibercept
Aflibercept is a recombinant fusion protein consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1.
Other Name: Eylea

Detailed Description:

Neovascular age-related macular degeneration (NV AMD) remains the leading cause of vision loss among people over 65. Intravitreal injections with drugs that block vascular endothelial growth factor (VEGF), a major protein mediator of angiogenesis and vascular leakage, have revolutionized treatment of NV AMD. This class of drugs includes the FDA-approved medications ranibizumab (Lucentis ®, Genentech) and aflibercept (Eylea ®, Regeneron), as well as bevacizumab (Avastin ®, Genentech), which is not FDA-approved for the treatment of NV AMD but is used off-label with demonstrated clinical efficacy. However, these therapies are not a cure. Even when effective, the vast majority of NV AMD patients require continued treatment with anti-VEGF drugs indefinitely for the rest of their lives, to sustain stable visual acuity. Further, in spite of continuous monthly anti-VEGF therapy, up to 40-50% of patients demonstrate persistent disease activity (PDA). Patients with persistent disease activity in spite of ongoing anti-VEGF therapy remain at increased risk for long-term vision loss. Persistent disease activity is defined as (1) unresolved intraretinal, subretinal, or sub-retinal pigment epithelium (RPE) fluid or exudation; (2) progressive lesion enlargement and fibrosis; and/or (3) persistent or new hemorrhage. Several large, multicenter, prospective clinical trials have demonstrated ~75% rate of PDA following loading dose therapy (i.e. three consecutive monthly injections), and ~ 40-50% PDA following one year of continued anti-VEGF therapy.

The treatment burden to sustain visual acuity for patients with PDA is especially high, since undertreatment or cessation of therapy assures visual decline. The PIER study assessed the efficacy of quarterly (i.e. every-three-months) anti-VEGF therapy with ranibizumab, following initiation with loading dose therapy. Patients who had resolution of disease activity following loading dose maintained visual acuity gains with subsequent quarterly therapy. In contrast, patients with PDA following loading dose had progressive loss of visual acuity gains when switched to subsequent quarterly therapy. Several subsequent clinical trials (CATT, IVAN, others) have demonstrated that patients with PDA typically require continued monthly therapy to sustain improved visual acuity. Though "do-able" in the short term, indefinite long-term therapy with monthly injections is often impractical for patients and for retina physicians, and as a result, undertreatment occurs with high frequency.

Verteporfin (Visudyne ®, Bausch + Lomb) PDT is an FDA-approved treatment for NV AMD that was initially approved over 10 years ago, prior to the advent of anti-VEGF therapy. As a first-line therapy, verteporfin PDT is much less effective than anti-VEGF therapy in improving vision for NV AMD patients. PDT has been studied as an adjunctive therapy in previously treatment-naïve patients receiving anti-VEGF therapy. It was not found to offer significant visual acuity benefit over anti-VEGF therapy alone, in this population. However, it is unknown whether adjunctive PDT may be effective in improving treatment response in patients with PDA in spite of anti-VEGF therapy. The investigators have performed several retrospective studies of NV AMD patients in the Duke Medical Retina practice to assess the role of adjunctive PDT in cases of PDA. Preliminary results indicate that adjunctive verteporfin PDT reduces disease activity (i.e. decreased fluid and exudation) in patients with PDA, facilitates treatment with fewer anti-VEGF injections (i.e. reduces treatment burden), and reduces risk of subsequent vision loss. However, no studies have prospectively evaluated the efficacy of adjunctive PDT in patients with PDA in spite of anti-VEGF therapy. The present study will assess the efficacy of adjunctive PDT for the treatment of PDA in NV AMD. The investigators will compare administration of anti-VEGF therapy with adjunctive PDT to the standard-of-care treatment approach, anti-VEGF monotherapy administered according to a "treat-and-extend" approach, where the interval between intravitreal injections is as short as every 1 month (approximately 4 weeks) but can be gradually lengthened to the longest interval between treatments that ensures disease quiescence.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical diagnosis of either 1) NV AMD with PDA in spite of standard-of-care intravitreal anti-VEGF therapy, either loading dose or maintenance therapy or 2) Clinical diagnosis of NV AMD with Progressive Disease in spite of standard-of-care intravitreal anti-VEGF therapy, either loading dose or maintenance therapy
  • Best-corrected visual acuity equivalent of 20/25-20/320
  • Able to provide written informed consent
  • Presence of discernible choroidal neovascular lesion by ICG angiography

Exclusion Criteria:

  • History of porphyria or sensitivity to any component of verteporfin preparation
  • Presence of systemic fungal infection or sensitivity to any component of triamcinolone acetonide preparation
  • Presence of ocular or periocular infection or sensitivity to any component to aflibercept
  • Prior vitrectomy surgery
  • Prior thermal laser for macular photocoagulation
  • Inability to avoid exposure of skin or eyes to direct sunlight or bright indoor light for 5 days following verteporfin PDT treatment sessions
  • Presence of large submacular hemorrhage in association with choroidal neovascular lesion
  • Known or suspected allergy to fluorescein and/or indocyanine green
  • Known history of open angle glaucoma
  • Known history of diabetic macular edema or macular edema attributable to central retinal vein occlusion
  • Recent history (within prior 6 months) of cerebrovascular accident (i.e. stroke) or myocardial infarction.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02457026


Locations
United States, North Carolina
Duke Eye Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Bausch & Lomb Incorporated
Investigators
Principal Investigator: Priyatham Mettu, MD Duke University
  More Information

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT02457026     History of Changes
Other Study ID Numbers: Pro00063930
First Submitted: May 21, 2015
First Posted: May 29, 2015
Last Update Posted: July 26, 2017
Last Verified: July 2017

Keywords provided by Duke University:
neovascular age-related macular degeneration
age-related macular degeneration
verteporfin
persistent disease activity
photodynamic therapy
Aflibercept

Additional relevant MeSH terms:
Macular Degeneration
Wet Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Triamcinolone hexacetonide
Triamcinolone
Triamcinolone Acetonide
Triamcinolone diacetate
Verteporfin
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Photosensitizing Agents
Dermatologic Agents