Combined aPproach to Treatment Using Ranibizumab and Efalizumab for Diabetic Macular Edema Study: The CAPTURE DME Study

Sponsor

Johns Hopkins University (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00676559

Collaborator

Juvenile Diabetes Research Foundation (Other), Genentech, Inc. (Industry)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study looks to continue the study of anti-vegf therapy in patients with macular edema, and compare it to an anti-inflammatory therapy and a combined Anti-vegf and anti-inflammatory.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Macular Edema	Drug: Efalizumab Drug: Ranibizumab	Phase 1

Detailed Description

Cell adhesion molecules are key mediators of inflammatory processes, which have been shown to play a role in the pathogenesis of diabetic retinopathy . Efalizumab inhibits the binding of leukocyte function-associated antigen-1 (LFA-1) to intercellular adhesion molecule-1 (ICAM-1) thereby inhibiting the adhesion of leukocytes to other cell types.

Clinical studies have demonstrated the bioactivities of intravitreal ranibizumab, a Vascular endothelial growth factor (VEGF) antagonist, in reducing retinal thickness and improving visual acuity in patients with diabetic macular edema (DME).

The objective of the CAPTURE Study is to assess the safety and tolerability of efalizumab, administered subcutaneously as a weekly (1 mg/kg) dose, compared to and in combination with ranibizumab, administered intravitreally (0.5 mg), in the treatment of DME.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Combined aPproach to Treatment Using Ranibizumab and Efalizumab for Diabetic Macular Edema Study: The CAPTURE DME Study

Study Start Date :

Apr 1, 2008

Anticipated Primary Completion Date :

Apr 1, 2009

Anticipated Study Completion Date :

Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Efalizumab 1 mg/kg weekly subcutaneous self-administered injections for 48 weeks.	Drug: Efalizumab Efalizumab 1 mg/kg weekly subcutaneous self-administered injections for 48 weeks. Other Names: Raptiva
Experimental: Group 2 Ranibizumab 0.5 mg intravitreal injections monthly for three months followed by criteria-guided monthly injections through Month 11 (inclusive).	Drug: Ranibizumab Ranibizumab 0.5 mg intravitreal injections monthly for three months followed by criteria-guided monthly injections through Month 11 (inclusive). Other Names: Lucentis
Experimental: Group 3 Efalizumab 1 mg/kg weekly subcutaneous self-administered injections for 48 weeks in combination with ranibizumab 0.5 mg intravitreal injections monthly for three months followed by criteria-guided monthly injections through Month 11 (inclusive).	Drug: Efalizumab Efalizumab 1 mg/kg weekly subcutaneous self-administered injections for 48 weeks. Other Names: Raptiva Drug: Ranibizumab Ranibizumab 0.5 mg intravitreal injections monthly for three months followed by criteria-guided monthly injections through Month 11 (inclusive). Other Names: Lucentis

Arm

Intervention/Treatment

Experimental: Group 1

Efalizumab 1 mg/kg weekly subcutaneous self-administered injections for 48 weeks.

Drug: Efalizumab

Efalizumab 1 mg/kg weekly subcutaneous self-administered injections for 48 weeks.

Other Names:

Raptiva

Experimental: Group 2

Ranibizumab 0.5 mg intravitreal injections monthly for three months followed by criteria-guided monthly injections through Month 11 (inclusive).

Drug: Ranibizumab

Ranibizumab 0.5 mg intravitreal injections monthly for three months followed by criteria-guided monthly injections through Month 11 (inclusive).

Other Names:

Lucentis

Experimental: Group 3

Efalizumab 1 mg/kg weekly subcutaneous self-administered injections for 48 weeks in combination with ranibizumab 0.5 mg intravitreal injections monthly for three months followed by criteria-guided monthly injections through Month 11 (inclusive).

Drug: Efalizumab

Efalizumab 1 mg/kg weekly subcutaneous self-administered injections for 48 weeks.

Other Names:

Raptiva

Drug: Ranibizumab

Ranibizumab 0.5 mg intravitreal injections monthly for three months followed by criteria-guided monthly injections through Month 11 (inclusive).

Other Names:

Lucentis

Outcome Measures

Primary Outcome Measures

To assess the safety and tolerability of efalizumab, compared to and in combination with ranibizumab, measuring the frequency and severity of adverse events. [6 mos]

Secondary Outcome Measures

To measure the mean change from Baseline to Month 6 and Month 12 in Best correct visual acuity (BCVA) [6 and 12 mos.]
To evaluate the anatomic retinal changes as assessed by color fundus photography, fluorescein angiography, and Optical Coherence Tomography (OCT) [6 mos and 12 mos]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed informed consent and authorization of use and disclosure of protected health information
18 years of Age
Diagnosis of diabetes mellitus (type 1 or type 2)
Serum HbA1c 5.5% within 12 months of randomization
Retinal thickening (diabetic macular edema) involving the center of the fovea
Diagnosis must be confirmed by fluorescein angiography and OCT images over 250
Best corrected visual acuity score in the study eye of 20/40 to 20/320
If a female of childbearing potential, a negative pregnancy test and commitment to the use of at least two forms of effective contraception.
If a non-sterile male, commitment to the use of two forms of effective contraception.
Demonstrate understanding of and ability to perform weekly self sub-cutaneous injections.

Exclusion Criteria:

Panretinal or macular photocoagulation within 3 months of study entry in the study eye
Use of intraocular or periocular injection of steroids in the study eye within 3 months of study entry
Previous participation in a study and receipt of anti-angiogenic drugs (pegaptanib sodium, ranibizumab, bevacizumab, anecortave acetate, protein kinase C inhibitor, etc.) within 2 months of study entry
Current or history of prior treatment of psoriasis with subcutaneous efalizumab within 6 months of study entry
Proliferative diabetic retinopathy in the study eye, with the exceptions of
inactive, fibrotic proliferative diabetic retinopathy that has regressed following pan-retinal laser photocoagulation OR
tufts of neovascularization elsewhere (NVE) less than one disc area with no vitreous hemorrhage
Vitreomacular traction or epiretinal membrane in the study eye
Structural damage to the center of the macula in the study eye likely to preclude improvement in visual acuity following the resolution of macular edema.
Concurrent disease in the study eye that could compromise visual acuity or require medical or surgical intervention during the first 6-months.
Cataract surgery in the study eye within 3 months of study entry; (YAG) laser capsulotomy within 1 month of study entry; or any other intraocular surgery within 3 months preceding Day 0.
History of vitreoretinal surgery in the study eye within 3 months of study entry
Uncontrolled glaucoma .
Blood pressure exceeding 180/100 (sitting) during the screening period
Uncontrolled diabetes mellitus, as evidenced by glycosylated hemoglobin > or = 13%(HbA1c) value
Renal failure requiring dialysis or renal transplant
Premenopausal women unwilling to commit to adequate contraception
History of other diseases or finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug, might affect interpretation of the results of the study, or render the subject at high risk from treatment complications
International Normalized Ratio (INR) > or = 3.0 (e.g. due to current treatment with warfarin).
History of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 6 months of study enrollment.
Have a history of hypersensitivity to efalizumab
Have a history of ongoing uncontrolled serious bacterial, viral, fungal, or atypical mycobacterial infection. Have a history of opportunistic infections.
Have the presence or history of malignancy, including lymphoproliferative disorders.
Have a history of thrombocytopenia, clinically significant hemolytic anemia, or unexplained anemia
Have a platelet count < 100,000 cells/microliter (uL)
Inability to comply
Patients receiving immunosuppressive agents
All acellular, live and live-attenuated vaccines are excluded from 14 days prior to the first dose of efalizumab until a minimum of 4 weeks after the last dose of efalizumab
Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated.
Participation in another simultaneous medical investigation or trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Diego H. Calonje, M.D., P.C.	Tucson	Arizona	United States	85712
2	Sharp Rees-Stealy Medical Group	San Diego	California	United States	92101
3	Retina Macula Institute	Torrance	California	United States	90503
4	Retina Associates of Maine	Bangor	Maine	United States	04401
5	Retina Center of Maine	South Portland	Maine	United States	04106
6	Wilmer Eye Institute at the Johns Hopkins University	Baltimore	Maryland	United States	21287
7	Ophthalmic Consultants of Boston	Boston	Massachusetts	United States	02114
8	Eye Care Specialists	Kingston	Pennsylvania	United States	18704
9	Texas Retina Associates	Arlington	Texas	United States	76012
10	University of Utah	Salt Lake City	Utah	United States	84132