Know Cancer

forgot password

Multi-Center Randomized Phase I/II Trial to Study the Effects of Cyclooxygenase-2 Inhibition on the Response to Photodynamic Therapy in Patients With Age-Related Macular Degeneration

Phase 2
Not Enrolling
Macular Degeneration

Thank you

Trial Information

Multi-Center Randomized Phase I/II Trial to Study the Effects of Cyclooxygenase-2 Inhibition on the Response to Photodynamic Therapy in Patients With Age-Related Macular Degeneration

Age-related macular degeneration (AMD) represents the most common cause of blindness in
patients over the age of 60. The major cause of vision loss in this disease is due to the
development of choroidal neovascularization. Several clinical trials have shown that eyes
with predominately 'well-defined' areas of neovascularization (lesions having at least 50%
of vessels which can be readily demarcated with fluorescein angiography) can benefit from
treatment with photodynamic therapy (PDT). However, this treatment benefit only results in
a reduction in the number of patients who suffer severe vision loss. Few patients
demonstrate an improvement in visual acuity. In addition, other neovascular lesions such as
those with predominate occult (vessels that are difficult to outline by fluorescein
angiography) or pure occult do not demonstrate any substantial treatment benefit.

Histopathologic studies have demonstrated the presence of an inflammatory response in the
retina of patients with choroidal neovascularization as well as in eyes receiving PDT. In
addition, in eyes receiving PDT, a vascular remodeling and continued neovascular process
occurs. Therefore, the use of celecoxib (Celebrex® (Registered Trademark)), a specific
cyclooxygenase-2 inhibitor, which possesses both anti-angiogenic as well as
anti-inflammatory properties, may be beneficial in patients with neovascular AMD undergoing

The study will be organized as a double-masked, randomized, placebo-controlled, prospective
multi-center clinical trial to investigate the ability of celecoxib to alter the
inflammatory and neovascular responses in AMD patients undergoing PDT. The results of this
study will contribute to the design of a larger definitive clinical trial. The primary
outcome measure is a drop of 15 letters or more in best corrected visual acuity following
initial PDT treatment at 1 year. The secondary outcome measures are stabilization (drop of
4 letters of less from baseline) or improvement of best corrected visual acuity following
initial PDT treatment at week 36, and an improvement by 5 or more letters in visual acuity
from baseline to week 36, time to retreatment with PDT, number of retreatments with PDT and
a change in the CNV size, the extent of leakage and staining detected by fluorescein
angiography. Additional outcome measures will be the change in size and extent of vascular
remodeling and choroidal new vessel formation as determined by optical coherence tomography
(OCT) and high-speed indocyanine green angiography (HS-ICG).

Inclusion Criteria


To participate in this study, the study participant must understand and sign the protocol
informed consent.

Age greater than or equal to 50 years.

In at least one eye, diagnosis of AMD defined by the presence of drusen larger than 63
micro milli.

The presence of choroidal neovascularization under the fovea determined by the Principal
Investigator of each clinical site and defined as any one of the following fluorescein
angiographic (FA) features:

1. Early stippled hyperfluorescence of flat retinal pigment epithelium with ill-defined
boundary and little or mild leakage in the late frames of the fluorescein (occult).

2. Irregular elevation of the retinal pigment epithelium that does not exhibit discrete
or bright hyperfluorescence in the early transit phase of the angiogram. Stippled
hyperfluorescence may be present. Late frames may show persistent fluorescein
staining or leakage within a sensory retinal detachment overlying this area (occult).

3. Late phase leakage of undetermined source with leakage at the level of the retinal
pigment epithelium in the late-frames of the angiogram in which the source of the
late leakage cannot be determined from earlier-phase frames of the angiogram

4. A well-demarcated area of bright hyperfluorescence in the early phase of the
angiograpm with leakage through the mid- and late- phase frames which obscures the
boundaries of the area (classic).

The greatest linear dimension of the entire lesion (classic CNV, occult CNV and any
features that could obscure the identification of classic or occult CNV has to be less
than or equal to 5400 micro milli in greatest linear dimension on the retina as measured
by the treating ophthalmologist. If the lesion is designated as entirely occult, then
additionally, the greatest linear dimension of the lesion must be greater than 525 micro
milli (total area of 1/2 disc area). Additionally, if the lesion is designated as
entirely occult then there should be 'presumed recent disease progression' that may
include the presence of blood from CNV, growth of the lesion (at least 10% increase in the
greatest linear dimension) or deterioration inVA (a one line loss) within the preceding 12

Visual acuity of 20/40 - 20/200 (66 - 34 letters) as measured on an ETDRS chart. If both
eyes are eligible then the eye with the worst visual acuity will be treated and considered
the study eye.

Retinal photographs and angiography of sufficient quality allowing assessment of the
macular area according to standard clinical practice can be obtained.


Choroidal neovascularization, in the study eye, associated with other ocular diseases such
as pathologic myopia, ocular histoplasmosis or posterior uveitis, etc.

Presence of geographic atrophy under the fovea in the study eye.

Decreased vision, the study eye, due to retinal disease not attributable to CNV, such as
nonexudative forms of ARM, geographic atrophy, inherited retinal dystrophy, uveitis or
epiretinal membrane.

Decreased vision, in the study eye, due to significant media opacity such as corneal
disease or cataract, or opacity precluding photography of the retina.

History of other antiangiogenic treatment of concomitant administration of other
experimental therapies for AMD other than nonfoveal confluent laser photocoagulation.

Presence of fibrosis, hemorrhage, pigment epithelial detachments, tear (rip) of the
retinal pigment epithelium or other hypofluorescent lesions obscuring greater than 50% of
the CNV lesion.

Prior PDT treatment in the study eye.

Any contraindications to performing the necessary diagnostic studies, especially the use
of fluorescein or indocyanine green angiography.

Allergy to iodine or previous iodine containing dyes.

Allergy to eggs.

Porphyria or other porphyrin sensitivity.

Medical problems that make consistent follow-up over the treatment period unlikely (e.g.,
stroke, severe MI, terminal carcinoma).

Current use of or likely need for systemic or ocular medications know to be toxic to the
lens, retina or optic nerve, such as:

1. Deferoxamine

2. Chloroquine/Hydroxychloroquine (Plaquenil)

3. Tamoxifen

4. Phenothiazine

5. Phenothiazines

6. Ethambutol

History of intra-cranial bleeds.

Positive urine pregnancy test or currently lactating for women of childbearing potential.

Current history of malignancy (except study participants having a basal cell carcinoma
that was treated successfully, or other malignancy operated on and in remission for 5
years prior to inclusion in the trial).

Use of tetracycline or doxycycline.

Intraocular surgery within the last 2 months or capsulotomy within the last month in the
study eye.

Use of any investigational drug within 30 days of enrollment.

Laboratory values outside normal limits and considered clinically significant by the

Malabsorption syndrome.

Celebrex, any other COX-2 inhibitor, NSAID, or ocular topical NSAID use greater than 3
days per week for a period of greater than or equal to 4 weeks within 2 weeks prior to
enrollment of likely need during the study. Aspirin greater than 81 mg/day is permitted
up to 1 week prior to enrollment and daily aspirin use of no more than 81 mg/day during
the study is permitted.

Allergy to sulpha-containing compounds, NSAIDs, or demonstration o the aspiring triad.

History of kidney disease (creatinine level greater than 2.5 dL, need for dialysis, or

Liver disease.

Concurrent use of warfarinor known bleeding diathesis.

History of inflammatory bowel disease.

Concurrent use of lithium.

History of peptic ulcer within 1 year prior to enrollment.

History of myocardial infarction 2 years prior to enrollment.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

August 2002

Completion Date:

January 2005

Related Keywords:

  • Macular Degeneration
  • Classic
  • Occult
  • Neovascular
  • Celecoxib
  • Age-Related Macular Degeneration
  • Photodynamic Therapy
  • Choroidal Neovascularization
  • Cyclooxygenase 2
  • Macular Degeneration
  • AMD
  • Age Related Macular Degeneration
  • Macular Degeneration



National Eye Institute (NEI) Bethesda, Maryland  20892