Ignite Creation Date:
2025-12-24 @ 4:15 PM
Ignite Modification Date:
2025-12-29 @ 5:03 AM
Study NCT ID:
NCT00726466
Status:
WITHDRAWN
Last Update Posted:
2015-07-07
First Post:
2008-07-29
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study of Efalizumab Combined With Intravitreal Ranibizumab in the Treatment of Age-Related Macular Degeneration
Sponsor:
Vitreous -Retina- Macula Consultants of New York
Organization:
Study Overview
Official Title:
A Phase I Study of the Inhibition of LFA-1 to Intercellular Adhesion Molecule-1 (ICAM-1) Using Subcutaneous Efalizumab Combined With Intravitreal Ranibizumab in the Treatment of Age-Related Macular Degeneration (SEIRA)
Status:
WITHDRAWN
Status Verified Date:
2015-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Lack of recruitment
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SEIRA
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.
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.
Detailed Description:
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. 10 subjects from 1 site will be enrolled in this study. Subject accrual into the trial is expected to be completed within 6 months.
All subjects will be evaluated monthly with a full ocular examination, visual acuity measurement (ETDRS chart at distance of 4 meters), OCT, and adverse event monitoring. Fluorescein Angiography (FA) and fundus photos will be done at BSL, Months 3, 6, 9 and 12.
Subjects will receive efalizumab 1mg/kg weekly subcutaneous injections for 24 weeks. Subcutaneous Efalizumab injections can be self administered after an initial teaching session in office on Day 0.
Subjects will receive six initial doses of 0.5 mg/eye intravitreous monthly injections of ranibizumab (Day 0, Months 1, 2, 3, 4 and 5) with scheduled follow-up visits monthly for 12 months. Re-treatment after the first six injections will be on an as-needed basis, based on predefined criteria.
3.2 RATIONALE FOR STUDY DESIGN
The rationale for the study is as follows:
* Phase III studies of patients with primary or recurrent choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) treated with repeated intravitreal injections of 0.5 mg of ranibizumab showed evidence for bioactivity, safety, and tolerability (Rosenfeld 2006);
* Phase III studies of patients with chronic moderate to severe plaque psoriasis treated with weekly subcutaneous efalizumab injections of 1mg/kg showed evidence for bioactivity, safety, and tolerability (Dubertret 2006);
* A Phase I study of patients with uveitis treated with subcutaneous efalizumab injections of 1mg/kg in patients with uveitic macular edema is currently enrolling (ClinicalTrials.gov Identifier: NCT00280826)
* Combination therapy of an iCAM-1 inhibitor and an anti-VEGF agent may offer increased treatment benefit in the management of age-related macular degeneration.
All subjects will be evaluated monthly with a full ocular examination, visual acuity measurement (ETDRS chart at distance of 4 meters), OCT, and adverse event monitoring. Fluorescein Angiography (FA) and fundus photos will be done at BSL, Months 3, 6, 9 and 12.
Subjects will receive efalizumab 1mg/kg weekly subcutaneous injections for 24 weeks. Subcutaneous Efalizumab injections can be self administered after an initial teaching session in office on Day 0.
Subjects will receive six initial doses of 0.5 mg/eye intravitreous monthly injections of ranibizumab (Day 0, Months 1, 2, 3, 4 and 5) with scheduled follow-up visits monthly for 12 months. Re-treatment after the first six injections will be on an as-needed basis, based on predefined criteria.
3.2 RATIONALE FOR STUDY DESIGN
The rationale for the study is as follows:
* Phase III studies of patients with primary or recurrent choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) treated with repeated intravitreal injections of 0.5 mg of ranibizumab showed evidence for bioactivity, safety, and tolerability (Rosenfeld 2006);
* Phase III studies of patients with chronic moderate to severe plaque psoriasis treated with weekly subcutaneous efalizumab injections of 1mg/kg showed evidence for bioactivity, safety, and tolerability (Dubertret 2006);
* A Phase I study of patients with uveitis treated with subcutaneous efalizumab injections of 1mg/kg in patients with uveitic macular edema is currently enrolling (ClinicalTrials.gov Identifier: NCT00280826)
* Combination therapy of an iCAM-1 inhibitor and an anti-VEGF agent may offer increased treatment benefit in the management of age-related macular degeneration.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: