Full Text View  
  Tabular View  
  Contacts and Locations  
  No Study Results Posted  
  Related Studies  
Infliximab, Sirolimus and Daclizumab to Treat Age-Related Macular Degeneration
This study is currently recruiting participants.
Verified by National Institutes of Health Clinical Center (CC), October 2008
Sponsored by: National Eye Institute (NEI)
Information provided by: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00304954
  Purpose

This study will examine whether the anti-inflammatory medicines infliximab, sirolimus or daclizumab, when given with a patient's current therapies, will prevent the growth of new blood vessels in the eye in patients with age-related macular degeneration (AMD).

Patients 55 years of age and older with AMD with drusen larger than 63um may be eligible for this study. Vision in the study eye must be between 20/20 and 20/400.

Participants are randomly assigned to one of three treatments - infliximab, sirolimus, or daclizumab - or to observation only. In addition, patients may be treated by their ophthalmologist as need for their AMD. Infliximab and daclizumab are given intravenously (through a vein); infusions are given at enrollment in the study, then at 2 weeks, and then monthly. Sirolimus is a pill that is taken every other day for the duration of the study. At 6 months patients are evaluated to see if continuing treatment would be beneficial.

In addition to treatment or observation, participants undergo the following procedures:

Physical examination at enrollment and 6 months.

Photos of the back of the eye, fluorescein angiography, indocyanine green studies, and measurement of retinal thickness at enrollment and months 1, 3 and 6.

  • Fluorescein angiography evaluates the eye's blood vessels. A yellow dye is injected into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina are taken using a camera that flashes a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating possible blood vessel abnormality.
  • Indocyanine green angiography identifies feeder vessels that may be supplying abnormal blood vessels. This procedure is similar to fluorescein angiography, but uses a green dye and flashes an invisible light.
  • Optical coherence tomography measures retinal thickness. This test shines a light into the eye and produces cross-sectional pictures of the retina. These measurements are repeated during the study to determine if retinal thickening is getting better or worse, or staying the same.

Tuberculin skin test and chest x-ray at enrollment and 6 months.

Blood tests at enrollment and months 1, 3 and 6.


Condition Intervention Phase
Macular Degeneration
Neovascularization
Drug: Daclizumab
Drug: Infliximab
Other: Observation
Drug: Sirolimus
Phase II

Genetics Home Reference related topics: X-linked juvenile retinoschisis
MedlinePlus related topics: Macular Degeneration
Drug Information available for: Sirolimus Infliximab Dacliximab
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study
Official Title: Treatment of Choroidal Subretinal Neovascularization With Agents Directed Against the Immune Response

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Recurrence of choroidal neovascularixzation as well as changae in visual acuity and retinal thickening. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Secondary effects [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: March 2006
Arms Assigned Interventions
1: Active Comparator
Biologic directed against parts of the immune system.
Drug: Daclizumab
N/A
2: Active Comparator
Biologic directed against parts of the immune system.
Drug: Infliximab
N/A
3: Active Comparator
Medication directed again parts of the immune system and new blood vessels.
Drug: Sirolimus
N/A
4
Observation with standard care.
Other: Observation
N/A

Detailed Description:

There has been much interest in the possible role of the immune system in age related macular degeneration. Experimental models and patient material have, to date, suggested a role for macrophages and complement. We hypothesize that the underlying mechanism that leads to choroidal neovascularization (CNV) is similar to those at play in atherosclerosis. If this is the case, then CNV treatment should be amenable to new immunomodulatory agents directed against specific parts of the immune system.

After therapy with anti-angiogenic agents not leading to a persistent remission of choroidal neovascularization due to age related macular degeneration, participants will be treated with one of three immunomodulatory agents or will be observed in conjunction with their continued anti-angiogenic therapy. Thus the participant will continue with the anti-angiogenic therapy they are receiving after randomization. We hypothesize that this combination therapy will inhibit progression of choroidal neovascularization (CNV) associated with age related macular degeneration (AMD).

This is an open-label, phase II, randomized, single center clinical trial of 20 study participants randomized to receive one of three immunomodulatory agents or will be observed in conjunction with their anti-angiogenic therapy.

  Eligibility

Ages Eligible for Study:   55 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

To be eligible for the study, participants must fulfill all of the following criteria:

  1. Understand and sign the IRB-approved informed consent document for the study.
  2. Age greater than 55 years.
  3. In the study eye, diagnosis of AMD defined by the presence of drusen larger than 63 microm.
  4. Any anti-angiogenic therapy in the study eye within 7 days of beginning immunosuppressive therapy.
  5. In the study eye, the participant's study eye vision is between 20/20 and 20/400.
  6. In the study eye, the presence of choroidal neovascularization under the fovea determined by NEI Investigators and defined as any one of the following fluorescein angiographic (FA) features:

    1. Early stippled hyperfluorescence of flat retinal pigment epithelium 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-phase frames of the angiogram in which the source of the late leakage cannot be determined from earlier-phase frames of the angiogram (occult).
    4. A well-demarcated area of bright hyperfluorescence in the early phase of the angiogram with leakage through the mid- and late-phase frames which obscures the boundaries of the area (classic).
  7. For all CNV lesions considered to have occult CNV with no classic CNV, one of the following criteria must be met:

    1. A documented loss of visual acuity (5 or more letters of best-corrected visual acuity if both measurements are made using an ETDRS chart or, a doubling of the visual angle if Snellen acuities are available from either an outside referral center or within the participating center (e.g., 20/80 to 20/160) a doubling of the visual angle is required because of the measurement variability of Snellen acuities).

      OR

    2. Documented fluorescein angiographic evidence of a 10% increase in the lesion greatest linear dimension over the 3 months prior to enrollment.

      OR

    3. Documented blood associated with CNV.
  8. 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 microm in greatest linear dimension on the retina as measured by the treating ophthalmologist.
  9. Retinal photographs and angiography of sufficient quality, allowing assessment of the macular area according to standard clinical practice, can be obtained.
  10. While unlikely, women of childbearing potential must not be pregnant or lactating, must have a negative pregnancy test at screening and must be practicing an adequate method of birth control. Acceptable methods of birth control include intrauterine device (IUD); oral, dermal, implanted or injected contraceptives; tubal ligation; and barrier methods with spermicide.
  11. Willingness to comply with the protocol.

EXCLUSION CRITERIA:

Participants meeting any of the following criteria will be excluded from the study:

  1. Choroidal neovascularization, in the study eye, associated with other ocular diseases such as pathologic myopaia, ocular histoplasmosis or posterior uveitis, etc.
  2. Presence of geographic atrophy under the fovea in the study eye.
  3. Evidence of retinal angiomatous proliferation as suspected by the presence of intraretinal hemorrhage, intraretinal leakage, adjoining serous PED or the presence of a connecting retinal vessel.
  4. The presence of a chorio-retinal anastomosis.
  5. Decreased vision, in the study eye, due to retinal disease not attributable to CNV, such as nonexudative forms of AMD, geographic atrophy, inherited retinal dystrophy, uveitis or epiretinal membrane. Participants who have any additional ocular diseases that have irreversibly compromised or, during follow-up, could likely compromise the VA of the study eye including amblyopia, anterior ischemic optic neuropathy, clinically significant diabetic macular edema, severe non-proliferative diabetic retinopathy, or proliferative diabetic retinopathy.
  6. Decreased vision, in the study eye, due to significant media opacity such as corneal disease or cataract, or opacity precluding photography of the retina; a tear (rip) of the RPE; a vitelliform-like lesion of the outer retina (e.g., as in pattern dystrophies or basal laminar drusen), idiopathic parafoveal telangiectasis, or central serous retinopathy.
  7. Presence of fibrosis, hemorrhage, pigment epithelial detachments and other hypofluorescent lesions obscuring greater than 50% of the CNV lesion.
  8. History of other systemic antiangiogenic treatment or treatment for CNV (not including photodynamic therapy and pegaptanib sodium injections) in the study eye with transpupillary thermotherapy or other local treatment (such as submacular surgery). Previous laser photocoagulation therapy is acceptable, provided it was not subfoveal.
  9. Participant with a known underlying systemic disease with evidence of serious or potentially lethal uncontrolled active disease in one or more extraocular organ systems for which a defined effective medical regimen is indicated.
  10. Participant with a corneal melting, necrotizing keratitis, or impending vision loss.
  11. Participants with history of allergy to/or exposure to mouse protein.
  12. Participant with scleritis of infectious etiology.
  13. Participant receiving any other investigational therapy or another anti-TNF agent that would interfere with the ability to evaluate the safety or efficacy of infliximab.
  14. Participant has significant active infection requiring hospitalization.
  15. Participant with multiple sclerosis.
  16. Participant has severe (class 3/4) congestive heart failure.
  17. Participant has a history of cancer within the past 5 years other than basal or squamous cell carcinoma.
  18. Participant is pregnant or lactating.
  19. Participant with posterior scleritis.
  20. Participant has evidence of liver disease (any etiology). History of moderate to severe abnormal liver function, unless documented evidence of normal liver enzymes is provided.
  21. Participant has positive PPD unless cleared by Internal Medicine.
  22. Participant has positive Chest X-ray showing acute pulmonary disease.
  23. Participant has unexplained hematuria.
  24. Participant has a history of alkylating therapy use.
  25. Current exam evidence of ocular toxoplasmosis; pseudoexfoliation; external ocular infection, including conjunctivitis; chalazion; significant blepharitis; or aphakia in the study eye (pseudophakic participants are eligible).
  26. Intraocular surgery (including lens replacement surgery) within 6 weeks prior to randomization.
  27. Recent history of (within the last 6 months), or current acute ocular or periocular infection (including any history of ocular herpes zoster or simplex).
  28. Known hypersensitivity/allergy to verteporfin, porfimer sodium, or other porphyrins, porphyria or other porphyrin sensitivity, or hypersensitivity to sunlight or bright artificial light. Participation in any other clinical study or are receiving, or have received any experimental systemic treatment for AMD (e.g.: retinoic acid, thalidomide). Local therapy for AMD is permitted.
  29. Medical problems that make consistent follow-up over the treatment period unlikely (e.g. stroke, severe MI, end stage malignancy), any contraindications to performing the necessary diagnostic studies (i.e., known allergy to fluorescein dyes etc.), or in general a poor medical risk because of other systemic diseases or active uncontrolled infections.
  30. Participant has a history of moderate to severe abnormal liver function, unless documented evidence of normal liver enzymes is provided.
  31. Participant has a history of active pulmonary tuberculosis.
  32. Participant has a history of active viral hepatitis.
  33. Participant has chronic continued Ketoconazole use.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00304954

Contacts
Contact: Patient Recruitment and Public Liaison Office (800) 411-1222 prpl@mail.cc.nih.gov
Contact: TTY 1-866-411-1010

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

NIH Clinical Center Detailed Web Page  This link exits the ClinicalTrials.gov site

Publications:
Responsible Party: National Institutes of Health ( Robert B. Nussenblatt, M.D./National Eye Institute )
Study ID Numbers: 060111, 06-EI-0111
Study First Received: March 17, 2006
Last Updated: December 25, 2008
ClinicalTrials.gov Identifier: NCT00304954  
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Age-Related Macular Degeneration
Ocular Inflammation
Rapamycin
Remicade
Daclizumab
Immunosuppression
Infliximab
Neovascularization
Sirolimus
Age-Related Macular Degeneration
AMD
Ocular Inflammation

Study placed in the following topic categories:
Sirolimus
Infliximab
Clotrimazole
Eye Diseases
Daclizumab
Miconazole
Tioconazole
Macular Degeneration
Retinal Degeneration
Inflammation
Metaplasia
Neovascularization, Pathologic
Retinal Diseases
Retinal degeneration

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Anti-Infective Agents
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Antibiotics, Antineoplastic
Immunosuppressive Agents
Pharmacologic Actions
Anti-Bacterial Agents
Pathologic Processes
Therapeutic Uses
Antifungal Agents
Antirheumatic Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on January 16, 2009