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

NCT02457026 | Withdrawn

• 1 other identifier: Pro00063930
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neovascular Age-related Macular Degeneration

Keywords

neovascular age-related macular degeneration; age-related macular degeneration; verteporfin; persistent disease activity; photodynamic therapy; Aflibercept

Outcome Measures

Primary Outcomes (3)

• Percentage of individuals with resolution or major reduction in PDA

  up to 8 weeks after loading dose

• Percentage of individuals with sustained visual acuity

  1 year after loading dose

• Average number of aflibercept injections

  1 year after loading dose

Secondary Outcomes (6)

• Frequency of case with progressive disease on therapy

  6 months post-PDT treatment

• Mean change in choroidal neovascularization lesion size by fluorescein angiography from baseline

  6 months post-PDT treatment

• Mean change in central foveal thickness by SD-OCT

  6 months post-PDT treatment

• Mean change in best-corrected ETDRS visual acuity from baseline

  6 months post-PDT treatment

• Percentage of participants with 2-line ETDRS visual acuity gain

  6 months post-PDT treatment

Study Arms (2)

Adjunctive PDT + Aflibercept

EXPERIMENTAL

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; Drug: Triamcinolone Acetonide; Drug: Verteporfin

Aflibercept Alone

ACTIVE COMPARATOR

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

Interventions

Aflibercept DRUG

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.

Also known as: Eylea

Adjunctive PDT + Aflibercept; Aflibercept Alone

Triamcinolone Acetonide DRUG

Triamcinolone Acetonide is a synthetic corticosteroid indicated for treatment of ocular inflammatory conditions, uveitis, sympathetic ophthalmia, and temporal arteritis.

Also known as: Triesence

Adjunctive PDT + Aflibercept

Verteporfin DRUG

Verteporfin is a benzoporphyrin derivative, and is a medication used as a photosensitizer for photodynamic therapy.

Also known as: Visudyne

Adjunctive PDT + Aflibercept

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Duke University: lead
• Bausch & Lomb Incorporated: collaborator

Study Sites (1)

Duke Eye Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Macular Degeneration

Interventions

aflibercept; Triamcinolone Acetonide; Triamcinolone; Verteporfin

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

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

• Priyatham Mettu, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2015
• First Posted: May 29, 2015
• Study Start: January 1, 2016
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: July 26, 2017

Record last verified: 2017-07

Locations

US (1)