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

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

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.

Study Overview

• Status: Unknown
• Conditions: Macular Degeneration; Diabetic Retinopathy
• Intervention / Treatment: Drug: intravitreal injection of infliximab

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 Type: Interventional
• Enrollment (Anticipated): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • SLingerlands, New York, United States, 12159
      • Recruiting
      • Retina Consultants
      • Contact: Paul Beer, MD; Phone Number: 518-533-6550
      • Principal Investigator: Paul M Beer, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
(BCVA)	3m
Standard Electroretinogram	3m
OCT	3m
Fluorescein angiography	3m
Nidek Microperimetry	3m
Incidence and severity of adverse events	3m

Collaborators and Investigators

• Sponsor: Retina Research Foundation

Publications and helpful links

Helpful Links

• Retina Research Foundation
• Retina Consultants

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Anticipated): December 1, 2008
• Study Completion (Anticipated): December 1, 2008

Study Registration Dates

• First Submitted: June 10, 2008
• First Submitted That Met QC Criteria: June 11, 2008
• First Posted (Estimate): June 12, 2008

Study Record Updates

• Last Update Posted (Estimate): June 12, 2008
• Last Update Submitted That Met QC Criteria: June 11, 2008
• Last Verified: June 1, 2008

More Information

Terms related to this study

• Keywords: AMD; Infliximab; Remicade; CNV; CSME; BDR
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Degeneration; Retinal Diseases; Uveal Diseases; Choroid Diseases; Metaplasia; Macular Degeneration; Diabetic Retinopathy; Macular Edema; Choroidal Neovascularization; Neovascularization, Pathologic; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Infliximab
• Other Study ID Numbers: 101606