Treatment of Refractory Diabetic Macular Edema With Infliximab

NCT00505947 | Terminated Phase 3 DMC

• 2 other identifiers: C0168X97EU-0129
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine if treatment with infliximab improves macular edema which is refractory to laser photocoagulation in patients with diabetes.

Conditions

Diabetic Macular Edema; Visual Acuity; Diabetic Retinopathy

Keywords

macular edema; diabetes mellitus; visual loss; diabetic retinopathy; macula; maculopathy; infliximab

Outcome Measures

Primary Outcomes (1)

• improvement in best corrected visual acuity

  32 weeks

Secondary Outcomes (1)

• anatomical improvement of diabetic macular edema and improvement in diabetic retinopathy

  32 weeks

Study Arms (2)

A

ACTIVE COMPARATOR

Infliximab 5 mg/Kg body weight by intravenous infusion on visit 1 (week 0), visit 2 (week 2), visit 3 (week 6)and visit 5 (week 14). Afterwards, after a washout period of 2 weeks, arm A will receive placebo at visits 6 (week 16), visit 7 (week 18), visit 8 (week 22)and visit 30 (week 30)

Drug: infliximab; Drug: placebo

B

PLACEBO COMPARATOR

Arm B will receive placebo at visit 1 (week 0), visit 2 (week 2), visit 3 (week 6)and visit 5 (week 14). Afterwards, after a washout period of 2 weeks, group B will receive infliximab 5 mg/Kg body weight by intravenous infusion at visit 6 (week 16), visit 7 (week 18), visit 8 (week 22)and visit 30 (week 30)

Drug: infliximab; Drug: placebo

Interventions

infliximab DRUG

infliximab 5 mg/Kg body weight by intravenous infusion

Also known as: Remicade

A; B

placebo DRUG

placebo 5 mg/Kg body weight by intravenous infusion

Also known as: placebo: a solution of similar appearance with infliximab

A; B

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have the capacity to understand and sign an informed consent form.
• Signed informed consent (must be obtained before any specific procedure is performed).
• Presence of clinically significant macular edema, with visual acuity less than 0.4 corrected to EDRS scale, which is refractory to at least two sessions of laser photocoagulation, defined as: A) Thickening of the retina at or within 500 μm of the center of the macula. B) Hard exudates at or within 500 μm of the center of the macula, if associated with thickening of the adjacent retina. C) A zone or zones of retinal thickening 1 disc area or larger, any part of which is within 1 disc diameter of the center of the macula.
• Male or female aged 18-80 years, inclusive.
• Type 1 or type 2 diabetes of at least 1 year duration. Type 1 diabetes is defined clinically as a diagnosis made before the age of 36 years with a continuous need for insulin within a year of diagnosis. Type 2 diabetes is defined clinically as a diagnosis made at age of 36 or above without a need for continuous insulin therapy within a year of diagnosis.
• Postmenopausal women (no menstrual cycle for a period of a minimum of 1 year) or surgically sterilized and have a negative serum pregnancy test on entry in the study. Men must agree to use adequate birth control during the study for 6 months after the infusion of the study agent.
• Men and women of childbearing potential must use adequate birth control measures (e.g. abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization) for the duration of the study and should continue such precautions for 6 months after receiving the last infusion.
• Stable diabetic therapy within the last 6 months, i.e. absence of major change in glycemic control (e.g. 2% change in HbA1c) or change in daily number of insulin injections.
• HbA1c 6.2-10%.
• The screening laboratory test must meet the following criteria: white blood cell count \>5x10/L; absolute neutrophil count \>1x10/L; platelet count \>50x10/L; haemoglobin \>100 g/L; serum creatinine \<2 mg/dl; aspartate aminotransferase \< 3 times the upper normal limit; alanine aminotransferase \<3 times the upper normal limit; alkaline phosphatase \< 2 times the upper normal limit, γ-GT\< 2 times the upper normal limit
• Patients are considered eligible according to the following tuberculosis (TB) screening criteria: A)Have no history of latent or active TB prior to screening. B)Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination. C)Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study agent. D) Within 1 month prior to the first administration of study agent, either have a negative tuberculin skin test, as outlined in appendix B, or have a newly identified positive tuberculin skin test during screening in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study agent. E)Have a chest radiograph (both posterior-anterior and lateral views), taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current active TB or old inactive TB.

You may not qualify if:

• Vitreoretinal traction.
• Retinal detachment.
• Proliferative diabetic retinopathy requiring immediate panretinal photocoagulation.
• Any previous eye surgery in the last 6 months before the beginning of the study (intravitreal injections are not considered ocular surgery).
• Macular Edema of ischaemic type.
• Macular Edema caused by retinal conditions other than diabetes.
• Cataract or media opacities of a degree which precludes accurate retinal photographs or OCT measurement.
• Hard exudates under the fovea.
• Uncontrolled hypertension (blood pressure above 180/110 mmHg).
• Angle closure glaucoma which precludes pharmacological dilatation of the pupil.
• Use in the previous 6 months of oral corticosteroids or in the previous month of anti-inflammatory medication.
• Women who are pregnant, nursing, or planning pregnancy within 6 months after the last infusion) (this includes fathers who plan on fathering a child within 6 months after their last infusion).
• Have had any previous treatment with monoclonal antibodies or antibody fragments.
• Documentation of seropositivity for human immunodeficiency virus (HIV).
• A positive test for hepatitis B surface antigen or hepatitis C virus (HCV).

Sponsors & Collaborators

• University of Athens: lead

Study Sites (2)

Medical School, University of Athens

Athens, 11527, Greece

Location

University of Athens

Athens, 11527, Greece

Location

Related Publications (1)

• Sfikakis PP, Grigoropoulos V, Emfietzoglou I, Theodossiadis G, Tentolouris N, Delicha E, Katsiari C, Alexiadou K, Hatziagelaki E, Theodossiadis PG. Infliximab for diabetic macular edema refractory to laser photocoagulation: a randomized, double-blind, placebo-controlled, crossover, 32-week study. Diabetes Care. 2010 Jul;33(7):1523-8. doi: 10.2337/dc09-2372. Epub 2010 Apr 22.

  PMID: 20413522 DERIVED

MeSH Terms

Conditions

Diabetic Retinopathy; Macular Edema; Diabetes Mellitus; Vision Disorders; Macular Degeneration

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Endocrine System Diseases; Retinal Degeneration; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Petros Sfikakis, MD

  University of Athens

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 23, 2007
• First Posted: July 25, 2007
• Study Start: July 1, 2007
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: February 20, 2009

Record last verified: 2009-02

Locations

GR (2)