Study of Efalizumab Combined With Intravitreal Ranibizumab in the Treatment of Age-Related Macular Degeneration

NCT00726466 | Withdrawn Phase 1

• 1 other identifier: FVF4385s
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Efalizumab is an immunosuppressive recombinant humanized IgG1 monocolonal antibody (150 Kd) that binds to human CD11a (1) and is used for the treatment of plaque psoriasis. Efalizumab was derived from the humanization of the murine efalizuman monoclonal antibody MHM24, which recognizes human and chimpanzee CD11a. Humanization of MHM24 was accomplished by grafting the murine complementarity determining regions (hypervariable region) into consensus human IgG1/ heavy and light chain sequences (Werther et al 1996). These same consensus human immunoglobulin sequences have been successfully used in the humanization of other murine antibodies, including those targeted to HER2 and IgE. Efalizumab inhibits the binding of LFA-1 to intercellular adhesion molecule-1 (ICAM-1) thereby inhibiting the adhesion of leukocytes to other cell types. Ranibizumab is a recombinant, humanized, Fab fragment of a mouse monoclonal antibody targeted against VEGF. As VEGF binds to cellular receptors, it stimulates angiogenesis and vascular leakage. Blockade of VEGF by ranibizumab leads to reduced stimulation of cell proliferation and permeability resulting in inhibition of angiogenesis and decreased leakage. Ranibizumab intravitreal administration in neovascular AMD patients has been shown to effectively reduce vascular leakage and growth of CNV and to stabilize or improve visual function. To further improve visual acuity, a combination therapy using efalizumab and ranibizumab is proposed. Efalizumab could target the adhesion factors that precede angiogenesis and improve the outcome for AMD patients in combination with the anti-VEGF agent, Ranibizumab.

Conditions

Age Related Macular Degeneration; AMD; CNV

Keywords

Age Related Macular Degeneration; AMD; CNV

Outcome Measures

Primary Outcomes (1)

• • Safety and tolerability of 0.5 mg intravitreal dose of Ranibizumab in combination with 1 mg/kg/wk subcutaneous dose of Efalizumab in the treatment of age-related macular degeneration using the incidence and severity of adverse events through Month 6.

Secondary Outcomes (1)

• The secondary outcomes of this study are as follows: • Mean change in ETDRS BCVA at Months 6 and 12. • Mean change in central retinal thickness per OCT at Months 6 and 12 • Mean change in lesion and CNV size as determined by FA at Months 6 and 12

Study Arms (1)

I

EXPERIMENTAL

This is an open-label, study of 0.5 mg intravitreal dose of Ranibizumab in combination with 1 mg/kg/wk subcutaneous dose of Efalizumab in in subjects with AMD.

Drug: Efalizumab, Ranibizumab

Interventions

Efalizumab, Ranibizumab DRUG

I

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide written informed consent and comply with study assessments for the full duration of the study.
• Demonstrate understanding of and ability to perform weekly self sub-cutaneous injections.
• Subjects of either gender, Age \> 50 years
• Best corrected visual acuity in the study eye between 20/40 and 20/320.
• Subfoveal choroidal neovascularization, secondary to age related macular degeneration. 6-10 anti-VEGF treatments allowed prior to enrollment.
• Presence of subretinal fluid and/or cystoid retinal edema on OCT.
• Presence of fibrosis, hemorrhage, serous pigment epithelial detachments, tear (rip) of the retinal pigment epithelium or other hypofluorescent lesions should not obscure greater than 50% of the CNV lesion.
• Annual immunization completed at least 4-6 weeks prior to BSL.
• Clear ocular media and adequate papillary dilation to permit good quality stereoscopic fundus photography
• Ability to return for all study visits

You may not qualify if:

• Pregnancy (positive pregnancy test) or lactation.
• Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch.
• Had prior treatment with Photodynamic Therapy (PDT).
• Had treatment with anti-VEGF agents within 30 days prior to BSL.
• Had treatment with Kenalog within 6 months prior to BSL.
• Had treatment with Dexamethaosne within 30 days prior to BSL.
• Had ocular surgery within the past 60 days in the study eye.
• Concurrent use of more than two therapies for glaucoma.
• Uncontrolled glaucoma in the study eye (defined as intraocular pressure \>30 mm Hg despite treatment with anti-glaucoma medication).
• Concurrent use of systemic anti-VEGF agents
• Has active infection in the study eye.
• Inability to obtain photographs to document CNV.
• Has received investigational therapy within 60 days prior to study entry.
• Patients with significantly compromised visual acuity in the study eye due to concomitant ocular conditions.
• Have a history of hypersensitivity to efalizumab or any of its components

Sponsors & Collaborators

• Vitreous -Retina- Macula Consultants of New York: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Vitreous Retina Macula Consultants of New York

New York, New York, 10022, United States

Location

Related Links

• Study site

MeSH Terms

Conditions

Macular Degeneration

Interventions

efalizumab; Ranibizumab

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jason S Slakter, MD

  Vitreous -Retina- Macula Consultants of New York

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 29, 2008
• First Posted: August 1, 2008
• Study Start: March 1, 2008
• Last Updated: July 7, 2015

Record last verified: 2015-07

Locations

US (1)