Efalizumab to Treat Uveitis

Macular Edema Clinical Trial

Official title:

Treatment of Non-Infectious Intermediate and Posterior Uveitis Associated Macular Edema With Humanized Anti-CD11a Antibody Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00280826
• Other study ID #: 060046
• Secondary ID: 06-EI-0046
• Status: Completed
• Phase: Phase 1
• First received: January 21, 2006
• Last updated: January 28, 2011
• Start date: January 2006
• Est. completion date: February 2009

Study information

• Verified date: January 2011
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: February 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Macular Edema
• Uveitis

Intervention

Drug:
• Efalizumab
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.

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Eye Institute (NEI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Djalilian AR, Nussenblatt RB. Immunosuppression in uveitis. Ophthalmol Clin North Am. 2002 Sep;15(3):395-404, viii. Review. — View Citation

Leonardi CL. Efalizumab: an overview. J Am Acad Dermatol. 2003 Aug;49(2 Suppl):S98-104. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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).	Baseline and 16 weeks	No
Secondary	Cystoid Macular Edema in the Better Eye as Assessed by Optical Coherence Tomography (OCT).	Better eye indicates the eye with better VA.	Baseline and 16 weeks	No
Secondary	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.	Baseline and 16 weeks	No
Secondary	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.	Baseline and 16 weeks	No