ITVR: Intravitreal Infliximab for Diabetic Macular Edema (DME) and Choroidal Neovascularization (CNV)

Sponsor

Retina Research Foundation (Other)

Overall Status

Unknown status

CT.gov ID

NCT00695682

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Injections of medicine into the middle of the eye (intravitreal injections) are commonly used in a multitude of retinal diseases. We are looking for new treatments that may be beneficial in treating retinal disease and improving patients' vision.

Infliximab (Remicade) is a genetically engineered antibody against a molecule in the body called TNF-α. It neutralizes the effects of TNF-α by binding to it. Intravenous Infliximab has been used for inflammatory arthritic conditions and Crohn's disease since 1998. We do not know if infliximab injections into the eye are safe. We are performing this pilot study to determine if they can be safe.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Retinopathy Macular Degeneration	Drug: intravitreal injection of infliximab	Phase 1

Detailed Description

Intravenous Infliximab is currently used for the treatment of systemic inflammatory conditions and inflammatory disease of the eye with a relatively favorable safety profile. However, systemic administration carries the risk of systemic side effects, which in the case of infliximab can be severe, such as increased risk of infection, reactivation of tuberculosis or Hepatosplenic T-cell Lymphoma.

Direct intravitreal administration of medication is the preferred method of treatment for retinal vascular disorders. The eye is a self contained organ relatively isolated from the systemic circulation by the tight blood retinal barrier. Effective intraocular drug levels can be achieved with a much smaller amount of medication if injected intravitreally and this also results in minimal systemic exposure to the patient. Preliminary studies have shown that Infliximab may have a positive role in the management of retinal vascular disorders in humans when administered intravenously, and can be an effective treatment intravitreally in animal models. No data has been published yet on intravitreal use of infliximab in human subjects.

We plan to study the safety and tolerability of intravitreal injections of infliximab in human subjects with refractory diabetic macular edema or choroidal neovascularization. Our infliximab dose will be 0.5mg/0.5ml, as it follows the reconstitution instructions in the Product Insert. This dosing will fall within the therapeutic dosing found within the animal study as it leads to the same vitreous concentration as the7.5 µg dose in group B rat eye study. (4)

Study Design

Study Type:

Interventional

Anticipated Enrollment :

4 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Safety and Tolerability of Intravitreal Infliximab (Remicade) in Patients With Refractory Diabetic Macular Edema or Choroidal Neovascularization Secondary to Age Related Macular Degeneration- A Pilot Study

Study Start Date :

Jun 1, 2008

Anticipated Primary Completion Date :

Dec 1, 2008

Anticipated Study Completion Date :

Dec 1, 2008

Outcome Measures

Primary Outcome Measures

This is a pilot study to study the safety and tolerability of intravitreal Infliximab in patients with refractory diabetic macular edema and choroidal neovascularization (CNV) [3 m]

Secondary Outcome Measures

(BCVA) [3m]
Standard Electroretinogram [3m]
OCT [3m]
Fluorescein angiography [3m]
Nidek Microperimetry [3m]
Incidence and severity of adverse events [3m]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ability to provide written informed consent and comply with study assessments for the full duration of the study
Age > 21 years
Patients with active CNV secondary to AMD in the study eye which did not improve with conventional therapy
Patients with refractory diabetic macular edema in the study eye which did not improve with conventional therapy
BCVA 20/70 or less as measured on an ETDRS chart.

Exclusion Criteria:

Are participating in another clinical study requiring follow up examinations
Have received any other experimental drug within 12 weeks prior to enrollment
Are unwilling or unable to follow or comply with all study-related procedures
Inability to obtain photographs, fluorescein angiography, or optical coherence tomography to document CNV, e.g. due to media opacity, allergy to fluorescein dye or lack of venous access
Aphakia or pseudophakia with the absence of posterior capsule (unless it resulted from a yttrium aluminum garner [YAG]) posterior capsulotomy)
Within two months prior to screening, have had intraocular surgery (including cataract surgery) in the study eye
Within 1 month prior to screening had YAG laser in the study eye
Have had intravitreal anti VEGF or intravitreal steroids in the last 6 weeks
Have had previous pars plana vitrectomy in the study eye
Are pregnant or are trying to become pregnant
Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
Have a history of allergies to murine monoclonal antibodies, mice or mouse products.