search
Back to results

Efalizumab to Treat Uveitis

Primary Purpose

Uveitis, Macular Edema

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Efalizumab
Sponsored by
National Eye Institute (NEI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Uveitis focused on measuring OCT, Retinal Disease, Adhesion Molecule, Ocular Inflammation, Raptiva, Macular Edema, Uveitis, Immunosuppression

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Participant is 18 years of age or older; Participant has a diagnosis of sight-threatening, intermediate or posterior uveitis of at least three months duration prior to original enrollment that is causing persistent cystoid macular edema in one or both eyes. Their disease requires treatment to control their intraocular inflammatory disease with at least 20 mg/day of prednisone (or equivalent) or any combination of two or more anti-inflammatory treatments for uveitis, including for example prednisone, cyclophosphamide, cyclosporine, azathioprine, mycophenolate mofetil, methotrexate, etc. Participant exhibits intolerance to the indicated systemic medications required for their uveitis or, though their uveitis may be under control, wish to be taken off their present medications due to potential or actual unacceptable side effects. Participant has visual acuity in at least one eye of 20/200 or better. Participant has normal renal or liver function or no worse than mild abnormalities as defined by the Common Toxicity Criteria. Participant is not currently pregnant or lactating. Both men and women with reproductive potential and who are sexually active agree to use acceptable birth control methods throughout the course of the study and for six weeks following the last administration of the study medication. Participant must have the ability to understand and sign an informed consent form. Exclusion Criteria: Participants who had received previous treatment with an intercellular adhesion molecule (ICAM) or lymphocyte function-associated antigen-1 (LFA-1) directed monoclonal antibody or any other investigational agent that would interfere with the ability to evaluate the safety, efficacy or pharmacokinetics of efalizumab. Participant has a significant active infection. Participant has a history of cancer (other than a non-melanoma skin cancer) diagnosed within the past 5 years.

Sites / Locations

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Efalizumab

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants With Systemic Toxicities, Adverse Events, or Infections
Safety outcomes were recorded by observing and tabulating the nature, severity and frequency of systemic toxicities, adverse events and infections throughout the study. Safety assessments were made by the investigators continuously during the study, with a review of the previous visit interval performed at each scheduled visit. Each participant was also encouraged to report any apparent adverse events between scheduled visits and could return for additional evaluations or treatment between scheduled visits if needed.

Secondary Outcome Measures

Cystoid Macular Edema in the Worse Eye as Assessed by Optical Coherence Tomography (OCT).
Worse eye indicates the eye with the worst visual acuity (VA).
Cystoid Macular Edema in the Better Eye as Assessed by Optical Coherence Tomography (OCT).
Better eye indicates the eye with better VA.
Change in Visual Acuity in the Worse Eye From Baseline to 16 Weeks
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. This acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters the Snellen measurement is 20/20.
Change in Visual Acuity in the Better Eye From Baseline to 16 Weeks
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. This acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters the Snellen measurement is 20/20.

Full Information

First Posted
January 21, 2006
Last Updated
January 28, 2011
Sponsor
National Eye Institute (NEI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00280826
Brief Title
Efalizumab to Treat Uveitis
Official Title
Treatment of Non-Infectious Intermediate and Posterior Uveitis Associated Macular Edema With Humanized Anti-CD11a Antibody Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
January 2011
Overall Recruitment Status
Completed
Study Start Date
January 2006 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
February 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
National Eye Institute (NEI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study examined the safety and potential efficacy of the monoclonal antibody efalizumab (Raptiva) for treating sight-threatening uveitis (eye inflammation). Efalizumab controls the activity of white blood cells called lymphocytes that cause inflammation. The drug is currently approved in the United States to treat patients with moderate to severe psoriasis. Participants 18 and older with sight-threatening intermediate or posterior uveitis of at least 3 months duration, causing persistent macular edema in one or both eyes, were eligible for this study. The uveitis required treatment with at least 20 milligrams per day of prednisone, or the equivalent, or a combination of two or more anti-inflammatory treatments such as prednisone, methotrexate, cyclophosphamide, cyclosporine, etc. Participants underwent the following tests and procedures: Medical history and physical examination. Weekly efalizumab treatment. Weekly eye examination, including measurement of vision and pressure in the eyes, dilation of the eyes and examination of the front and back parts of the eye. Weekly blood tests to measure the number and types of cells in the blood and to check for signs of inflammation and treatment side effects. At some visits, blood samples were collected to measure how much efalizumab remains in the blood and whether the body has developed an immune response to the medicine. Blood draw at enrollment and at 2 and 4 months for research tests to examine how participants' immune response was operating. Fluorescein angiography at enrollment and 1 and 3 months after enrollment, unless additional tests are needed, for medical management. This test checked for abnormalities of eye blood vessels. A yellow dye was injected into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina (the back portion of the eye) were taken with a special camera that flashes a blue light into the eye. The pictures show whether any dye has leaked from the vessels into the retina, indicating possible abnormalities. Monthly pregnancy test for women who could become pregnant. Participants returned for treatment and clinic visits weekly for 16 weeks. After 16 weeks, participants whose macular edema had decreased and whose vision may have improved were offered to continue the injections.
Detailed Description
Background: Uveitis refers to intraocular inflammatory diseases that are an important cause of visual loss. Standard systemic immunosuppressive medications for uveitis can cause significant adverse effects. Consequently, an effective treatment with a safer side effect profile is highly desirable. Aims: This protocol evaluated the safety and potential efficacy of subcutaneous (SC) efalizumab (anti-CD11a) treatments for uveitis while reducing or eliminating standard medications commensurate with the standard of care. If the therapeutic benefit was sustained using the SC formulation, then maintenance therapy was continued as clinically indicated. Methods: This was an open-label, non-randomized, clinical pilot study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Uveitis, Macular Edema
Keywords
OCT, Retinal Disease, Adhesion Molecule, Ocular Inflammation, Raptiva, Macular Edema, Uveitis, Immunosuppression

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Efalizumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Efalizumab
Other Intervention Name(s)
Raptiva
Intervention Description
Participants who qualified for the study received weekly subcutaneous treatments of efalizumab, with the first dose being a test dose of 0.7 mg/kg and subsequent doses of 1 mg/kg (not to exceed 200 mg per dose), for a total treatment duration of 16 weeks.
Primary Outcome Measure Information:
Title
Number of Participants With Systemic Toxicities, Adverse Events, or Infections
Description
Safety outcomes were recorded by observing and tabulating the nature, severity and frequency of systemic toxicities, adverse events and infections throughout the study. Safety assessments were made by the investigators continuously during the study, with a review of the previous visit interval performed at each scheduled visit. Each participant was also encouraged to report any apparent adverse events between scheduled visits and could return for additional evaluations or treatment between scheduled visits if needed.
Time Frame
16 weeks
Secondary Outcome Measure Information:
Title
Cystoid Macular Edema in the Worse Eye as Assessed by Optical Coherence Tomography (OCT).
Description
Worse eye indicates the eye with the worst visual acuity (VA).
Time Frame
Baseline and 16 weeks
Title
Cystoid Macular Edema in the Better Eye as Assessed by Optical Coherence Tomography (OCT).
Description
Better eye indicates the eye with better VA.
Time Frame
Baseline and 16 weeks
Title
Change in Visual Acuity in the Worse Eye From Baseline to 16 Weeks
Description
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. This acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters the Snellen measurement is 20/20.
Time Frame
Baseline and 16 weeks
Title
Change in Visual Acuity in the Better Eye From Baseline to 16 Weeks
Description
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. This acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters the Snellen measurement is 20/20.
Time Frame
Baseline and 16 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participant is 18 years of age or older; Participant has a diagnosis of sight-threatening, intermediate or posterior uveitis of at least three months duration prior to original enrollment that is causing persistent cystoid macular edema in one or both eyes. Their disease requires treatment to control their intraocular inflammatory disease with at least 20 mg/day of prednisone (or equivalent) or any combination of two or more anti-inflammatory treatments for uveitis, including for example prednisone, cyclophosphamide, cyclosporine, azathioprine, mycophenolate mofetil, methotrexate, etc. Participant exhibits intolerance to the indicated systemic medications required for their uveitis or, though their uveitis may be under control, wish to be taken off their present medications due to potential or actual unacceptable side effects. Participant has visual acuity in at least one eye of 20/200 or better. Participant has normal renal or liver function or no worse than mild abnormalities as defined by the Common Toxicity Criteria. Participant is not currently pregnant or lactating. Both men and women with reproductive potential and who are sexually active agree to use acceptable birth control methods throughout the course of the study and for six weeks following the last administration of the study medication. Participant must have the ability to understand and sign an informed consent form. Exclusion Criteria: Participants who had received previous treatment with an intercellular adhesion molecule (ICAM) or lymphocyte function-associated antigen-1 (LFA-1) directed monoclonal antibody or any other investigational agent that would interfere with the ability to evaluate the safety, efficacy or pharmacokinetics of efalizumab. Participant has a significant active infection. Participant has a history of cancer (other than a non-melanoma skin cancer) diagnosed within the past 5 years.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Nussenblatt, MD, MPH
Organizational Affiliation
National Eye Institute (NEI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
12434489
Citation
Djalilian AR, Nussenblatt RB. Immunosuppression in uveitis. Ophthalmol Clin North Am. 2002 Sep;15(3):395-404, viii. doi: 10.1016/s0896-1549(02)00036-6.
Results Reference
background
PubMed Identifier
12894132
Citation
Leonardi CL. Efalizumab: an overview. J Am Acad Dermatol. 2003 Aug;49(2 Suppl):S98-104. doi: 10.1016/s0190-9622(03)01141-1.
Results Reference
background
PubMed Identifier
7641842
Citation
Whitcup SM, Hikita N, Shirao M, Miyasaka M, Tamatani T, Mochizuki M, Nussenblatt RB, Chan CC. Monoclonal antibodies against CD54 (ICAM-1) and CD11a (LFA-1) prevent and inhibit endotoxin-induced uveitis. Exp Eye Res. 1995 Jun;60(6):597-601. doi: 10.1016/s0014-4835(05)80001-6.
Results Reference
background
PubMed Identifier
21498606
Citation
Faia LJ, Sen HN, Li Z, Yeh S, Wroblewski KJ, Nussenblatt RB. Treatment of inflammatory macular edema with humanized anti-CD11a antibody therapy. Invest Ophthalmol Vis Sci. 2011 Sep 1;52(9):6919-24. doi: 10.1167/iovs.10-5896.
Results Reference
derived

Learn more about this trial

Efalizumab to Treat Uveitis

We'll reach out to this number within 24 hrs