Efalizumab to Treat Uveitis

NCT00280826 | Completed Phase 1 Results DMC

• 2 other identifiers: 06004606-EI-0046
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Uveitis; Macular Edema

Keywords

OCT; Retinal Disease; Adhesion Molecule; Ocular Inflammation; Raptiva; Macular Edema; Uveitis; Immunosuppression

Outcome Measures

Primary Outcomes (1)

• 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.

  16 weeks

Secondary Outcomes (4)

• Cystoid Macular Edema in the Worse Eye as Assessed by Optical Coherence Tomography (OCT).

  Baseline and 16 weeks

• Cystoid Macular Edema in the Better Eye as Assessed by Optical Coherence Tomography (OCT).

  Baseline and 16 weeks

• Change in Visual Acuity in the Worse Eye From Baseline to 16 Weeks

  Baseline and 16 weeks

• Change in Visual Acuity in the Better Eye From Baseline to 16 Weeks

  Baseline and 16 weeks

Study Arms (1)

Efalizumab

EXPERIMENTAL

Drug: Efalizumab

Interventions

Efalizumab DRUG

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.

Also known as: Raptiva

Efalizumab

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Eye Institute (NEI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 12434489 BACKGROUND

• Leonardi CL. Efalizumab: an overview. J Am Acad Dermatol. 2003 Aug;49(2 Suppl):S98-104. doi: 10.1016/s0190-9622(03)01141-1.

  PMID: 12894132 BACKGROUND

• 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.

  PMID: 7641842 BACKGROUND

• 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.

  PMID: 21498606 DERIVED

MeSH Terms

Conditions

Uveitis; Macular Edema; Retinal Diseases

Interventions

efalizumab

Condition Hierarchy (Ancestors)

Uveal Diseases; Eye Diseases; Macular Degeneration; Retinal Degeneration

Results Point of Contact

• Title: Robert Nussenblatt, MD, MPH
• Organization: National Eye Institute

drbob@intra.nei.nih.gov

301-496-3123

Study Officials

• Robert Nussenblatt, MD, MPH

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: January 21, 2006
• First Posted: January 23, 2006
• Study Start: January 1, 2006
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: February 2, 2011
• Results First Posted: January 27, 2011

Record last verified: 2011-01

Locations

US (1)